Cardiovascular Flashcards
Mention the layers of the heart from inner to outer layer
Endocardium
Myocardium
Visceral layer of serous pericardium
Pericardial cavity
Parietal layer of serous pericardium
Fibrous pericardium
Endocardium
1) Endothelium -> simple squamous epithelial tissue with areolar connective tissue
2) Functions
o Prevents blood in heart from clotting -> releases PGI2 and NO which inhibits platelet activation and aggregation.
o Act as a barrier between blood and tissue.
o Makes tight junctions which controls movement between cells.
o Continues as endothelium in blood vessels
o Lines the outer layer of the valves in the heart
Myocardium
1) Cardiac muscle tissues:
a. Contractile Cardiac Muscle
b. Non-Contractile Cardiac Muscle
o SA node -> nodal, auto-rhythmic cells, that can generate AP and set sinus rhythm
o AV node
o Bundle of His
o Bundle branches (right and left)
o Purkinje fibers
2) Functions:
a. Non-Contractile cardiac muscle -> generates and conducts action potentials.
b. Contractile cardiac muscle -> contracts as a unit to pump blood through and out of the heart.
Visceral layer of serous pericardium
o Also called epicardium
o Mesothelium: simple squamous with loose areolar connective tissue
o Secretes pericardial serous fluid into the cavity to lubricate tissue layers.
Pericardial cavity
o Contains serous fluid - usually has no blood under normal physiologic conditions.
o Prevents friction from two serous layers rubbing against each other.
Parietal layer of the serous pericardium
o Continuous with the epicardium
o Mesothelium: simple squamous + loose areolar connective tissue
o Secretes pericardial serous fluid into the cavity to lubricate tissue layers.
Fibrous pericardium
Tissue -> dense fibrous irregular connective tissue
Function:
o Anchors heart to surrounding structures
o Prevents heart from overfilling with blood because it’s not a distensible or “stretchy” tissue
o Protects the heart because it is a tough tissue
From where does the RA receives blood?
Received deoxygenated blood from three vessels:
o Cranial Vena Cava -> brings blood from structures above the diaphragm (head and neck and forelimbs)
o Caudal Vena Cava -> brings blood from structures below the diaphragm (abdomen, liver, hindlimb)
o Coronary Sinus -> brings blood from coronary circulation
From where does the LA receives blood?
Receives oxygenated blood from 4 pulmonary veins
o Two left pulmonary veins from the left lung
o Two right pulmonary veins from the right lung
Auricles
1) Left Auricle or left atrial appendage -> increases space and volume of right atrium. Thrombi very commonly forms here in heart disease (especially cats)
2) Right auricle or right atrial appendage -> increases space and volume of right atrium. Thrombi formation happens but not as common.
Heart valves / chordae tendineae / papillary muscle structure
1) Valve structure -> they are four annulus rings of fibrous tissue, and leaflets tissue hang from these annulus rings.
2) Chordae tendineae
o Anchors the leaflets to papillary muscles
o Collagen cords of connective tissue
o Attached to the cusps of the valves
o Keeps valve tight to prevent them from ballooning back into the atrium and causing blood backflow
3) Papillary muscles
o Projections of the myocardium
o Anchors the chordae tendineae
o If ischemic, muscles weaken -> unable to contract -> valve flaps loosen -> valve regurgitation
Atrioventricular valves
Between atria and ventricles -> prevents backflow of blood from ventricles into atria.
1) Tricuspid Valve -> between RA and RV. Contains three leaflets
2) Bicuspid or Mitral Valve -> between LA and LV. Contains two leaflets
Semilunar valves
o Have three crescent shaped cusps
o Between ventricles and pulmonary trunk and aorta
o Pulmonary trunk splits into the left and right pulmonary arteries
o Aorta -> Ascending aorta -> aortic arch -> descending aorta
1) Pulmonary Semilunar valve -> between RV and Pulmonary trunk
2) Aortic Semilunar Valve -> between LV and Ascending Aorta.
o Two coronary arteries arise from the aorta just beyond the semilunar valves;
o During diastole, the increased aortic pressure above the valve’s forces blood into the coronary arteries and thence into the musculature of the heart.
T/F The atrial and ventricular types of muscle contract in much the same way as skeletal muscle, except that the duration of contraction is much longer
TRUE
4 pacemakers in the heart?
SA node
AV node
Bundle of His
Purkinje fibers
The body decides who is the pacemaker is whoever is faster:
The SA node is normally 70-80 bpm
AV node 40-60bpm
Bundle of His about 40bpm
Purkinje fibers 15bpm
Therefore normally, the SA node is the one who dictates the HR and purkinje fibers is as a last resource in case the other pacemakers do not work.
What is the purpose of the gap junctions within the intercalated discs?
o Cardiac muscle is striated, similar to skeletal muscle but with some differences
o Cardiac muscle is a syncytium -> the muscle fibers are separated by intercalated discs (cell membranes that separate individual cardiac muscle cells)
o At each intercalated disc, the cell membrane fuse with one another to form permeable “communicating” junctions called “gap junctions”
o Gap junctions allow rapid diffusion of ions -> action potential travels rapidly.
How many syncytium is the heart composed off?
Two: atrial (walls of the 2 atria) and ventricular (walls of the 2 ventricles) syncytium.
T/F - The action potential recorded in a ventricular muscle fiber averages about 105mV, which means that the intracellular potential rises from a very negative value, about −85mV, between beats to a slightly positive value, about +20mV during each beat
TRUE
For how long the membrane rests depolarized?
0.1-0.2sec or 100-200milisec
That creates a plateau, typical of ventricular muscle cell action potential
What are the consequences of the plateau in ventricular action potentials?
Causes ventricular contraction to last as much as 15 times more compared to skeletal muscle
What are the major differences between cardiac and skeletal muscle that account for the differences in action potential?
o Action potential of skeletal muscle is caused almost entirely by the sudden opening of fast Na channels. They are called fast because they remain open for only a few thousands of a second and then they close.
o In cardiac muscle, the action potential is due to the opening of TWO type of channels:
* Same fast Na channels as in skeletal muscle
* L-type Ca channels (also called calcium-Na channels)
o The L-type Ca channels differs from the fast sodium channels in that they are slower to open (that is why there is a brief depolarization when K starts going out as Ca channels are slow to open) and, even more important, remain open for several tenths of a second.
o During this time, a large quantity of both calcium and sodium ions flows through these channels to the interior of the cardiac muscle fiber, and this activity maintains a prolonged period of depolarization, causing the plateau in the action potential
o The second major difference -> immediately after the onset of the action potential, the permeability of the cardiac muscle membrane for potassium ions decreases about fivefold, an effect that does not occur in skeletal muscle.
o The decreased potassium permeability greatly decreases the outflux of positively charged potassium ions during the action potential plateau and thereby prevents early return of the action potential voltage to its resting level - again, helps maintain the plateau phase.
What happens when the L-type Ca channels close?
o They close at the end of 0.2 to 0.3 second
o The influx of calcium and sodium ions ceases -> the membrane permeability for potassium ions also increases rapidly.
o This rapid loss of potassium from the fiber immediately returns the membrane potential to its resting level, thus ending the action potential.
Summary of phases of ventricular action potential
o Phase 0 (depolarization), fast sodium channels open. When the cardiac cell is stimulated and depolarizes, the membrane potential becomes more positive. Voltage-gated Na channels (fast Na channels) open and permit Na to rapidly flow into the cell and depolarize it. The membrane potential reaches about +20 millivolts before the Na channels close.
o Phase 1 (initial repolarization), fast Na channels close. The Na channels close, the cell begins to repolarize, and K ions leave the cell through open K channels.
o Phase 2 (plateau), Ca channels open and fast K channels close. A brief initial repolarization occurs and the action potential then plateaus as a result of increased Ca permeability and decreased K permeability. The voltage-gated Ca channels open slowly during phases 1 and 0, and Ca enters the cell. Potassium channels then close, and the combination of decreased K efflux and increased Ca influx causes the action potential to plateau.
o Phase 3 (rapid repolarization), Ca channels close and slow K channels open. The closure of Ca channels and increased K permeability, permitting K to rapidly exit the cell, ends the plateau and returns the cell membrane potential to its resting level.
o Phase 4 (resting membrane potential) averages about −90 millivolts.
What does it means “excitation-contraction coupling”?
o Refers to the mechanism by which the action potential causes the myofibrils of muscle to contract.
What is the sarcolemma
True cell membrane surrounding each muscle fiber
Each muscle fiber contains hundreds to thousands of muscle myofibrils
What is the sarcoplasm
The spaces between the myofibrils are filled with intracellular fluid called sarcoplasm
It contains larges amounts of K, Mg and Ph and a lot of mitochondria that supply with energy for the contraction.
Differences between cardiac / skeletal “excitation-contraction coupling”
o Same as for skeletal muscle, when an action potential reaches the cardiac muscle membrane, it spreads to the interior of the cardiac muscle fiber along the membranes of the transverse (T) tubules.
o The T tubule action potentials in turn act on the membranes of the longitudinal sarcoplasmic tubules to cause release of calcium ions into the muscle sarcoplasm from the sarcoplasmic reticulum.
o The calcium will promote sliding of the actin and myosin filaments along one another, which produces the muscle contraction.
o In the cardiac muscle, addition to the calcium ions that are released into the sarcoplasm from the cisternae of the sarcoplasmic reticulum, calcium ions also diffuse into the sarcoplasm from the T tubules themselves at the time of the action potential, which opens voltage-dependent calcium channels in the membrane of the T tubule.
o Ca entering the cell then activates Ca release channels (ryanodine receptor channels), in the sarcoplasmic reticulum membrane, triggering the release of Ca into the sarcoplasm. Calcium ions in the sarcoplasm then interact with troponin to initiate cross-bridge formation and contraction.
o Without the calcium from the T tubules, the strength of cardiac muscle contraction would be reduced considerably because the sarcoplasmic reticulum of cardiac muscle is less well developed than that of skeletal muscle and does not store enough calcium to provide full contraction.
When Ca2+ enters the cardiac muscle cell, what is the name of the receptors they activate to produce more release of Ca2+ from the sarcoplasmic reticulum?
Ryanodine receptor channel
Once relaxation occurs, how does Ca2+ gets out of the cell? How is the electrical gradient maintained?
Via the NCX anti porter (3Na in, 2Ca out)
Via the Na/K ATPase
T/F - The strength of skeletal muscle contraction is hardly affected by moderate changes in extracellular fluid Ca2+ concentration because skeletal muscle contraction is caused almost entirely by Ca2+ released from the sarcoplasmic reticulum inside the skeletal muscle fiber.
TRUE
How much is the delay in conduction to pass the impulse from the atrium to the ventricles?
0.1 sec
This delay is important to allow the atria contract ahead of the ventricles, therefore pumping blood into them.
What is the cardiac cycle?
Events that occur from the beginning of one heartbeat to the beginning of the next one.
T/F - Increasing HR decreases the duration of the cardiac cycle
TRUE
Which phase of the cardiac cycle is greatly reduced when HR increases? Why is that important?
o The duration of the action potential and the systole decreases, but not by as great a percentage as does the diastole.
o Because the heart beating at a very fast rate does not remain relaxed long enough to allow complete filling of the cardiac chambers before the next contraction.
How much % of blood flows into the ventricles before the atria contract?
80%
How much % of blood the contraction of the atria adds to the ventricular filling?
20%
T/F - The atria function as primer pumps that increase the ventricular pumping effectiveness as much as 20 percent. However, the heart can continue to operate under most conditions even without this extra 20 percent.
TRUE - when the atria fail to function, the difference is unlikely to be noticed unless a person exercises.
What is the “a wave”
Is caused by atrial contraction. The right atrial pressure increases 4 to 6 mm Hg during atrial contraction, and the left atrial pressure increases about 7 to 8 mm Hg.
What is the “c wave”
Occurs when the ventricles begin to contract; it is caused partly by slight back flow of blood into the atria at the onset of ventricular contraction but mainly by bulging of the A-V valves backward toward the atria because of increasing pressure in the ventricles.
What is the “v wave”
Occurs toward the end of ventricular contraction; it results from slow flow of blood into the atria from the veins while the A-V valves are closed during ven- tricular contraction. Then, when ventricular contraction is over, the A-V valves open, allowing this stored atrial blood to flow rapidly into the ventricles and causing the v wave to disappear.
What is the rapid filling of the ventricles?
As soon as systole is over and the ventricular pressures fall to their low diastolic values, the moderately increased pressures that have developed in the atria during ventricular systole immediately push the A-V valves open and allow blood to flow rapidly into the ventricles.
How long does it last the rapid filling?
1/3 of the diastole
Isovolumetric contraction
o Immediately after ventricular contraction begins, the ventricular pressure rises abruptly causing the A-V valves to close.
o Then an additional 0.02 to 0.03 second is required for the ventricle to build up sufficient pressure to push the aortic and pulmonary valves open against the pressures in the aorta and pulmonary artery.
o Therefore, during this period, contraction is occurring in the ventricles, but no emptying occurs. Cardiac muscle tension is increasing but little or no shortening of the muscle fibers is occurring.
Ejection period
When the LV pressure rises slightly above 80 mm Hg (and the RV pressure rises slightly above 8 mm Hg), the ventricular pressures push the semilunar valves open. Immediately, blood begins to pour out of the ventricles.
How much is the % of blood from the end of diastole that is ejected during systole?
60%
Difference between rapid and slow ejection?
o 70% of the blood ejected by the ventricles flows out during the first third of the ejection period -> rapid ejection period.
o Remaining 30% empties during the next 2/3 of systole -> slow ejection period.
Isovolumetric relaxation
o At the end of systole, ventricular relaxation begins suddenly, allowing both the right and left intraventricular pressures to decrease rapidly.
o The elevated pressures in the distended large arteries that have just been filled with blood from the contracted ventricles immediately push blood back toward the ventricles, which snaps the aortic and pulmonary valves closed.
o For another 0.03 to 0.06 second, the ventricular muscle continues to relax, even though the ventricular volume does not change as the AV valves are still closed -> period of isovolumic or isometric relaxation.
o During this period, the intraventricular pressures rapidly decrease back to their low diastolic levels. Then the A-V valves open to begin a new cycle of ventricular pumping.
End-diastolic volume
o During diastole, normal filling of the ventricles increases the volume of each ventricle to about 110 to 120mL.
o This volume is called the end- diastolic volume.
Stroke volume
o As the ventricles empty during systole, the volume decreases about 70mL, which is called the stroke volume output.
End systolic volume
o The remaining volume in each ventricle after systole, about 40 to 50mL
Ejection fraction
The fraction of the end-diastolic volume that is ejected — usually equal to about 0.6 (or 60 percent).
T/F - When the heart contracts strongly, the end-systolic volume may decrease to as little as 10 to 20mL
TRUE
T/F - When large amounts of blood flow into the ventricles during diastole, the ventricular end-diastolic volumes can become as great as 150 to 180mL in the healthy heart.
TRUE
T/F - Both increasing the end-diastolic volume and decreasing the end-systolic volume, the stroke volume output can be increased to more than double that which is normal.
TRUE
T/F - The heart valves open actively when blood flow is needed
FALSE - They close and open passively. They close when a backward pressure gradient pushes blood backward, and they open when a forward pressure gradient forces blood in the forward direction.
T/F - The A-V valves require almost no backflow to cause closure, whereas the much heavier semilunar valves require rather rapid backflow for a few milliseconds.
TRUE
T/F - The papillary muscles relax when the ventricles contract
FALSE - They contract when the ventricular walls contract.
T/F - The papillary muscles help close the valves
FALSE - they pull the valves inward toward the ventricles to prevent their bulging too far backward toward the atria during ventricular contraction.
Differences of semilunar valves and AV valves
o High pressures in the arteries at the end of systole cause the semilunar valves to snap closed, in contrast to the much softer closure of the A-V valves.
o Because of smaller openings, the velocity of blood ejection through the aortic and pulmonary valves is far greater than that through the much larger A-V valves.
o Because of the rapid closure and rapid ejection, the edges of the aortic and pulmonary valves are subjected to much greater mechanical abrasion than are the A-V valves.
o The A-V valves are supported by the chordae tendineae, which is not true for the semilunar valves.
T/F - The entry of blood into the arteries during left ventricular systole causes the walls of these arteries to stretch and the pressure to increase to about 120 mm Hg.
TRUE
What is the incisura
o An incisura occurs in the aortic pressure curve when the aortic valve closes.
o This is caused by a short period of backward flow of blood immediately before closure of the valve, followed by sudden cessation of the back flow.
Diastolic aortic pressure
Around 80mmHg
First heart sound
Close of AV valves
Second heart sound
Close of semilunar valves
Above which left ventricular volume the diastolic pressure starts increasing rapidly?
150mL
Partly because of fibrous tissue in the heart that will stretch no more and partly because the pericardium that surrounds the heart becomes filled nearly to its limit.
At what volume the left ventricle has his maximal systolic pressure?
150-170mL
o As the volume increases further, the systolic pressure actually decreases, because at these great volumes, the actin and myosin filaments of the cardiac muscle fibers are pulled apart far enough that the strength of each cardiac fiber contraction decreases.
LV volume / intraventricular pressure graph - draw and explain
Maximum systolic pressure for left ventricle
250-300mmHg
Maximum systolic pressure for right ventricle
60-80mmHg
Draw and explain the volume-pressure diagram
Cardiac preload
Usually considered to be the end-diastolic pressure when the ventricle has become filled.
Cardiac afterload
o The pressure in the aorta leading from the ventricle.
o Sometimes the afterload is loosely considered to be the resistance in the circulation rather than the pressure.
Why is the rate of oxygen consumption by the heart an excellent measure of the chemical energy liberated while the heart performs its work?
Because approximately 70 to 90 percent of this energy is normally derived from oxidative metabolism of fatty acids, with about 10 to 30 percent coming from other nutrients, especially lactate and glucose.
Which mechanism are used to control how much volume of blood to pump?
1) Intrinsic cardiac regulation of pumping in response to changes in volume of blood flowing into the heart - Frank Starling mechanism and increased stretch of RA.
2) Control of HR and contractility by the ANS
Venous return
Amount of blood that flows into the heart from the veins
T/F Each peripheral tissue of the body controls its own local blood flow, and all the local tissue flows combine and return by way of the veins to the right atrium.
TRUE
How is it called the heart’s intrinsic ability to adapt to increasing volumes of inflowing blood?
Frank-Starling mechanism of the heart.
What does the Frank-Starling mechanism means
That the greater the heart muscle is stretched during filling, the greater is the force of contraction and the greater the quantity of blood pumped into the aorta.
Explain the Frank-Starling mechanism and the RA stretch.
o When an extra amount of blood flows into the ventricles, the cardiac muscle is stretched to a greater length.
o This stretching in turn causes the muscle to contract with increased force because the actin and myosin filaments are brought to a more nearly optimal degree of overlap for force generation.
o Therefore, the ventricle, because of its increased pumping, automatically pumps the extra blood into the arteries.
o This ability of stretched muscle, up to an optimal length, to contract with increased work output is characteristic of all striated muscle, not only the cardiac muscle.
o Stretch of the right atrial wall directly increases the heart rate by 10 to 20 percent, which also helps increase the CO, although its contribution is much less than that of the Frank-Starling mechanism.
Right and left ventricular volume output curves - draw and explain
Describe the control of the heart by the sympathetic system
o The pumping effectiveness of the heart also is controlled by the sympathetic and parasympathetic (vagus) nerves.
o Sympathetic nerves -> can increase the heart rate from the normal rate of 70bpm up to 180 to 200 and, rarely, 250bpm.
o Sympathetic stimulation increases the force of heart contraction to as much as double the normal rate -> increases the volume of blood pumped and increases the ejection pressure.
o Sympathetic stimulation often can increase the maximum cardiac output as much as twofold to threefold, in addition to the increased output caused by the Frank-Starling mechanism.
o Inhibition of the sympathetic nerves to the heart can decrease cardiac pumping to a moderate extent. Under normal conditions, the sympathetic nerve fibers to the heart discharge continuously at a slow rate that maintains pumping at about 30 percent above that with no sympathetic stimulation.
o When the activity of the sympathetic nervous system is depressed below normal, both the heart rate and strength of ventricular muscle contraction decrease, decreasing the level of cardiac pumping as much as 30 percent below normal
Describe the control of the heart by the parasympathetic system
o Strong stimulation of the parasympathetic nerve fibers in the vagus nerves to the heart can stop the heartbeat for a few seconds, but then the heart usually “escapes” and beats at a rate of 20 to 40 beats/min as long as the parasympathetic stimulation continues.
o In addition, strong vagal stimulation can decrease the strength of heart muscle contraction by 20 to 30 percent.
o The vagal fibers are distributed mainly to the atria and not much to the ventricles, where the power contraction of the heart occurs -> the effect of vagal stimulation is mainly to decrease the heart rate rather than to decrease the strength of contractility.
o However, the great decrease in heart rate combined with a slight decrease in contractility can decrease ventricular pumping 50% or more.
Effect of sympathetic and parasympathetics stimulation on the cardiac function curve - draw and explain
o The ventricular function curves here represent the function of the entire heart rather than of a single ventricle.
o It shows the relation between right atrial pressure at the input of the right heart and cardiac output from the left ventricle into the aorta.
o At any given right atrial pressure, the cardiac output increases during increased sympathetic stimulation and decreases during increased parasympathetic stimulation.
Effects of excess K in the extracellular fluid on the heart
o Heart becomes dilated and flaccid and slows heart rate down.
o Large quantities of potassium can block conduction of the cardiac impulse from the atria to the ventricles through the A-V bundle.
o Elevation of K to only 8 to 12 mEq/L can cause severe weakness of the heart, abnormal rhythm, and death.
o High extracellular fluid potassium concentration partially depolarizes the cell membrane, causing the membrane potential to be less negative.
o As the membrane potential decreases, the intensity of the action potential also decreases, which makes contraction of the heart progressively weaker.
Effects of excess Ca in the extracellular fluid on the heart
o Excess calcium ions cause effects almost exactly opposite to those of potassium ions, causing the heart to move toward spastic contraction.
o This effect is caused by a direct effect of calcium ions to initiate the cardiac contractile process.
o Deficiency of calcium ions causes cardiac weakness, similar to the effect of high potassium.
o Calcium ion levels in the blood normally are regulated within a very narrow range.
Effect of temperature on heart function
o Increased body temperature (like fever,) greatly increases the heart rate, sometimes to double the normal rate.
o Decreased temperature greatly decreases heart rate, which may fall to as low as a few beats per minute when a person is near death from hypothermia in the body temperature range of 60° to 70°F.
o These effects presumably result from the fact that heat increases the permeability of the cardiac muscle membrane to ions that control heart rate, resulting in acceleration of the self-excitation process.
o Contractile strength of the heart often is enhanced temporarily by a moderate increase in temperature, such as that which occurs during body exercise, but prolonged elevation of temperature exhausts the metabolic systems of the heart and eventually causes weakness.
o Optimal function of the heart depends greatly on proper control of body temperature.
Sinus node
o Small, flattened, ellipsoid strip of specialized cardiac muscle localized on the right atrium.
o The fibers of this node have almost no contractile muscle filaments
o The sinus nodal fibers connect directly with the atrial muscle fibers so that any action potential that begins in the sinus node spreads immediately into the atrial muscle wall.
What is the automaticity of the heart?
o Some cardiac fibers have the capability of self-excitation -> can cause automatic rhythmical discharge and contraction.
o This capability is especially true of the fibers of the heart’s specialized conducting system, including the fibers of the sinus node.
o The sinus node ordinarily controls the rate of beat of the entire heart.
Resting membrane potential of sinus nodal fiber and ventricular fibers
o Sinus nodal fiber between discharges has a negativity of about −55 to −60mV
o Ventricular fibers at −85 to −90mV
o The reason is that the cell membranes of the sinus fibers are naturally leaky to Na and Ca (leak IN), and positive charges of the entering Na and Ca neutralize some of the intracellular negativity.
Differences between ventricular and SA action potentials
o At -55mV (SA node), fast Na channels are probably inactivated -> any time the membrane potential remains less negative than about −55 millivolts for more than a few milliseconds, the inactivation gates on the inside of the cell membrane close the fast Na channels and remain so.
o Only the slow Ca channels can open and cause the action potential.
o As a result, the atrial nodal action potential is slower to develop than the action potential of the ventricular muscle.
o After the action potential does occur, return of the potential to its negative state occurs slowly as well, rather than the abrupt return that occurs for the ventricular fiber.
Explain how the nodal fibers are self-excitable
o Because of the high Na concentration in the extracellular fluid outside the nodal fiber, as well as a moderate number of already open sodium channels, positive sodium ions from outside the fibers normally tend to leak to the inside.
o Therefore, between heartbeats, influx of positively charged sodium ions causes a slow rise in the resting membrane potential in the positive direction.
o The resting potential gradually rises and becomes less negative between each two heartbeats.
o When the potential reaches a threshold voltage of about −40mV, the L-type calcium channels become activated, thus causing the action potential.
o Therefore, the inherent leakiness of the sinus nodal fibers to sodium and calcium ions causes their self-excitation.
How are those fibers not depolarized constantly if they have Na and Ca leaky channels?
o Two events occur to prevent such a constant state of depolarization.
1) The L-type Ca channels close within about 100 to 150msec after opening.
2) At about the same time, greatly increased numbers of potassium channels open.
o Both of these effects reduce the intracellular potential back to its negative resting level and therefore terminate the action potential.
Hyperpolarization of SA node fibers
o The potassium channels remain open for another few tenths of a second, temporarily continuing movement of positive charges out of the cell.
o That results in excess negativity inside the fiber -> hyperpolarization.
o The hyperpolarization state is what carries the resting membrane potential down to about −55 to −60mV at the termination of the action potential.
Vasomotor tone effectors
Overview of cardiovascular neurohormonal control
Vasomotor center - medulla oblongata I
Baroreceptors
T/F - When there is hypertension, the nucleus tracts solitarius will stimulate the SNS and inhibit the PNS
FALSE - it will inhibit the SNS causing vasodilation and stimulate the PNS causing bradycardia
T/F During hypotensive states, the NTS it is unable to inhibit the SNS therefore there is vasoconstriction and unable to stimulate PNS therefore tachycardia is seen
TRUE
Autonomic nervous system general organization
ANS and cardiac myocytes
ANS and blood vessels - I
ANS and vasculature - II
o The endothelium communicates with the vascular smooth muscle.
Parasympathetic NS receptors
Heart muscarinic receptors
Main function of muscarinic 2 receptors
Inhibition
o Stimulation of M2 receptors leads to inability of the Gs protein to stimulate adenylate cyclase to produce cAMP
T/F - Ach binding to M2 vascular receptors will increase NO, producing vasodilation.
TRUE
Primary effect on VENOUS vascular tone, does not regulate arterial BP.
T/F - NE is a catecholamine derived from the amino acid tyrosine
TRUE
T/F - NE is synthesized within the nerve axon and stored within vesicles
TRUE
What is the rate limiting step in the production of NE?
The conversion of tyrosine to DOPA via the enzyme tyrosine hydroxylase
NE from never terminals vs NE from adrenal glands
Where can adrenergic receptors be located?
o Presynaptic - like the alpha2 that modulate the release of NE
o Postsynaptic - on effector organs
Postsynaptic adrenergic receptors
o Junctional - immediately associated with a sympathetic nerve (nerve -> tissue)
o Non-junctional - not directly associated with a nerve - mainly affected by circulating E/NE
T/F - Adrenergic receptor - 2 identical receptors can have entirely different effects depending on what tissue they are located on, even if G protein is the same
TRUE
Effects of different pressors
Norepinephrine and alpha receptors
Alpha 1 and alpha 2 adrenoreceptors
Presynaptic alpha 2 receptors
T/F - Postsynaptic alpha 1 receptors are inhibited by phenoxybenzamine and prazosin
TRUE
T/F - Presynaptic alpha 2 receptors are ________ (stimulated/inhibited) by dexmedetomidine and _______ (stimulated/inhibited) by yohimbine / antisedan
Stimulated
Inhibited
Non-alpha adrenergic receptors coupled to a Gq protein
B adrenoreceptors
B adrenoreceptors location
B1 and Gs protein
Other stimulants of cAMP in the heart
Other stimulants of cAMP
Why glucagon can be used in B blocker overdose?
Because all B receptors will be blocked, and glucagon can have the same effects -> increase cAMP -> increase HR and contractility, independent of the B receptors
T/F - B receptors in heart and in smooth muscle both use Gs protein but have opposite effects B1 and B2 -> B1 in heart will cause contraction, B2 in vascular smooth muscle, vasodilation
TRUE
Vascular smooth muscle B-adrenoreceptors
Adrenergic receptor comparison
Vasculature G protein pathways and drugs
What do kinase enzymes do?
Add a phosphorus - phosphorylates
What do phosphates enzymes do?
Remove phosphate group from its substrate - dephosphorylation -> opposite of kinases. Usually inactivates.
Clinically relevant 2nd messengers
GCRP subfamilies
GCRP - cyclase
GPCR - Phosphodiesterases
GPCS - kinases
T/F - cAMP is important in the heart because it will not only activate pkA and release intracellular calcium, but it will also act on the L-tye voltage calcium channels allowing more Ca to come in
TRUE
Gi pathway
Gq pathway
Cardiac G protein 2nd messengers
How does myocyte B1 stimulation and increased cAMP will increase HR?
o It will increase the rate of depolarization increasing the If (funny current)
o Opening of L-type voltage gated Ca channels - lower threshold potential
How does acetylcholine, Gi and decreased cAMP causes decrease in HR?
o Decreases in If (funny current) -> decreased rate of depolarization
o Inhibition of L-type voltage gated Ca channels -> increases threshold
o Activation of GIRKach (K channels) -> membrane hyperpolarization
Effects of ANS on AV node action potential
T/F - Gq can contribute to myocardial hyperthrophy
TRUE
T/F - Vascular tone -> we will have vasoconstriction any time the Gq protein is stimulated
TRUE
E/NE -> alpha 1 receptors
Vasopressin -> V1 receptors
Ach -> M3 -> if it binds M2 on the endothelial effects -> release of NO, vasodilation
AgII -> AT1
ET1 (endothelin 1) -> ETA
T/F - Vascular tone - with Gs protein we will have vasodilation
TRUE
Vasculature smooth muscle contraction and relaxation -> actions of pkA
Via myosin light chain kinase, MLCK (phosphorylation of myosin -> vasocontration) and myosin phosphatase, MMP (dephosphorylation of myosin -> vasodilation).
T/F - Smooth muscle contraction is myosin regulated
TRUE
Once myosin is phosphorylated it allows a good positioning of acting and myosin.
T/F - Cardiac muscle is actin regulated
TRUE
Change in conformation in the troponin complex and contraction can occur
TN-C -> calcium binding site -> regulates contraction
TN-I -> inhibits active site on actin
TN-T -> tropomyosin binding protein
G protein mediated smooth muscle contraction
G protein mediated smooth muscle relaxation
Phosphodiesterases overview
Phosphodiesterase inhibitors
Methylated xantines
o Non-selective PDEI
o- Chocolate components (theobromine), theophylline - spread effects throughout the body - increased cAMP generalized - increased HR and BP
Pimobendan effects
o Calcium sensitizer -> troponin regulatory complex does a better job binding Ca -> increase contractility w/o increasing intracellular calcium.
o Vascular smooth muscle vasodilator -> via PDEI3, increased cAMP
NO overview
Types of NO
NO mediated vasodilation - I
NO mediated vasodilation II
sGC - soluble guanyl cyclase
NO in disease states
Types of muscle fibers
o Thick filament regulated - myosin
o Thin filament regulated - troponin complex on actin
Name of the pump that puts Ca back in the sarcoplasmic reticulum so muscles can relax
SERCA2
Inhibited by phospholamban -> more Ca in cytosol
If phospholamban is inactivated -> more Ca pumped in the SR -> B adrenergic stimulation is one of the ways with increased relaxation
Because in the next cycle there will be more Ca in the SR, more Ca will be released -> increase force of contraction
This is how there is both increased lusitropy and inotropy
Pumps involved in cardiac cycle
What is Bachmann’s bundle
o A branch of the internodal tract
o From the right atrium directed towards the left atrium
Distribution of blood flow in different parts of the circulatory system
Basic principles of circulatory function
o Blood flow to most tissues is controlled according to the tissue need. When a particular tissue demands increased flow -> the microvessels of each tissue continuously monitor tissue needs, and in turn act directly on the local blood vessels, dilating or constricting them, to control local blood flow.
o Cardiac output is the sum of all local tissue flows
o Arterial pressure regulation is generally independent of either local blood flow control or cardiac output control.
Blood flow through a vessel is determined by?
o Pressure difference of the blood between the 2 ends of the vessel (pressure gradient)
o Vascular resistance - as a result of the friction between the flowing blood and the intravascular endothelium
o Can be calculated using Ohm’s law:
F = P1-P2 / R
Be also familiar with
o R = P1-P2 / F
o P1-P2 = F x R
What is laminar flow and its consequences
o When blood flows at a steady rate through a long, smooth blood vessel, it flows in streamlines, with each layer of blood remaining the same distance from the vessel wall.
o When laminar flow occurs, the velocity of flow in the center of the vessel is far greater than that toward the outer edges.
o The fluid in the middle of the vessel can move rapidly because many layers of slipping molecules exist between the middle of the vessel and the vessel wall; thus, each layer toward the center flows progressively more rapidly than the outer layers.
When does turbulent flow develops
o When the rate of blood flow becomes too great, when it passes by an obstruction in a vessel, when it makes a sharp turn, or when it passes over a rough surface.
o The blood flows crosswise in the vessel and along the vessel, usually forming whorls in the blood, called eddy currents.
o The blood flows with much greater resistance -> eddies add tremendously to the overall friction of flow in the vessel.
What does the Reynold’s number tell us
o The measure of the tendency for turbulence to occur
o Proportional to velocity of blood flow (v, in cm/sec), diameter (d, in cm) of blood vessel and density of blood
o Inversely proportional to viscosity of blood (in poise).
o If it is > 2000 -> turbulence will happen in a straight, smooth vessel
o Normally between 200-400 -> turbulent flow will occur at some branches but die pretty quick.
Conversion mmHg to cmH2O
1mmHg = 1.36cm H2O
Conductance of a vessel?
Inverse of resistance
C = 1/R
Poiseuille’s law
o F is the rate of blood flow.
o ΔP is the pressure difference between the ends of the vessel.
o r is the radius of the vessel.
o l is length of the vessel.
o η is viscosity of the blood.
o The rate of blood flow is directly proportional to the fourth power of the radius of the vessel.
Factors that will affect blood viscosity, therefore blood flow?
Hematocrit and plasma proteins
What is blood flow autoregulation?
The ability of each tissue to adjust its vascular resistance and to maintain normal blood flow during changes in arterial pressure between approximately 70 and 175 mmHg
T/F - The veins are much more distensible than the arteries.
TRUE - the veins, on average are about eight times more distensible than the arteries.
Vascular compliance
o The total quantity of blood that can be stored in a given portion of the circulation for each mm Hg pressure rise
o Vascular compliance = increase in V / increase in P
Main factors affecting pulse pressure?
o Stroke volume
o Compliance of the arterial tree
Pulse pressure = stroke volume / arterial compliance
Abnormal pressure pulse contours - draw and explain
Why is no incisura in the aortic pulse contour with aortic regurgitation?
Because there is no aortic valve to close
T/F Pressure pulses are damped in the smaller arteries, arterioles and capillaries
TRUE
o The cause of this damping is for 2 reasons:
1) Resistance to blood movement in the vessels. the greater the resistance, the more difficult the flow.
2) Compliance of the vessels -> the more compliant a vessel, the greater the quantity of blood required at the pulse wave front to cause an increase in pressure.
o The degree of damping is almost directly proportional to the product of resistance times compliance.
What are the Korotkoff sounds?
o Caused mainly by blood jetting through the partly occluded vessel (when measuring a BP) and by vibrations of the vessel wall.
o The jet causes turbulence in the vessel beyond the cuff, and this turbulence sets up the vibrations heard through the stethoscope.
T/F - MAP - it is not equal to the average of systolic and diastolic pressure because at normal heart rates, a greater fraction of the cardiac cycle is spent in diastole than is systole
TRUE
What is the central venous pressure?
Pressure in the RA
What determines movement through the capillary membrane?
Starling forces:
Capillary and interstitial hydrostatic pressure
Capillary and interstitial oncotic presure
What is vasomotion?
o Intermittent contraction of the metarterioles and precapillary sphincters
o Blood usually does not flow continuously through the capillaries. Instead, it flows intermittently, turning on and off every few seconds or minutes due to vasomotion
How is vasomotion regulated?
o The most important factor affecting the degree of opening and closing of the metarterioles and precapillary sphincters is the concentration of oxygen in the tissues.
o When the rate of oxygen usage by the tissue is great so that tissue oxygen concentration decreases below normal, the intermittent periods of capillary blood flow occur more often, and the duration of each period of flow lasts longer.
T/F - The capillaries in various tissues have extreme differences in their permeabilities.
TRUE - for example, the membranes of the liver capillary sinusoids are so permeable that even plasma proteins pass through these walls, almost as easily as water and other substances.
What are the factors that short term, regulate or affect the autoregulation of local tissue blood flow?
o Oxygen -> reduced O2 availability causes vasodilation
o Autoregulation of blood flow:
* Metabolic theory -> if BP increases -> too much flow -> too much nutrients -> washes out vasodilatory substances -> vasoconstriction
* Myogenic mechanism -> present in other organs too -> high BP -> stretch of blood vessels -> vasoconstriction
o Endothelial-derived substances (relaxing or constricting factors):
* NO -> released from healthy endothelial cells in response to different stimuli
* Endothelin -> released from damaged endothelium and causes vasoconstriction.
What are the factors that long term, regulate or affect the autoregulation of local tissue blood flow?
o Changes in tissue vascularity - creating new vessels as a result of a chronic increased demand of blood flow.
o Development of collateral circulation - when a blood vessel gets blocked
o Vascular remodeling in response to chronic changes in BP / blood flow
Humoral control of circulation
Vasoconstrictor agents:
E/NE
AgII
Vasopressin
Vasodilatory agents:
Bradykinin
Histamine
Define bradyarrhythmia
Bradycardia associated with clinical sings (dog <60bpm, cats <100bpm)
DDX for bradyarrhythmias
Alterations in autonomic tone
Electrolyte imbalances
Drug exposure
Trauma
Hypoxia
Inflammation / infiltration of myocardium
Degenerative disease of the conduction system
T/F Sinus bradycardia is normally secondary to systemic disease
TRUE
What is a wandering pacemaker?
Changes in p wave amplitude in relation to the respiratory cycle and it is normally when vagotonia is the cause of bradycardia
Sick sinus syndrome
o Disease of the conduction system
o Periods of normal SR or sinus bradycardia
o Periods of long sinus arrest that can last up to 10-12 seconds because junctional and ventricular pacemakers fail to initiate escape beats.
o Variant - bradycardia tachycardia syndrome -> periods of paroxysmal tachycardia followed by a temporal failure of the sinus rhythm to resume when tachycardia ends.
* It is due to an exaggerated normal physiologic response of the sinus node to the effect of the tachyarrhythmia - called overdrive suppression
o Old mini Schnauzers and Terrier breeds commonly affected by SSS
1st degree AV block
o Prolonged PR interval
o AV node fibrosis, increased vagal tone, drugs that delay AV conduction (digoxin, Ca channel blockers, B blockers)
2nd degree AV block
o When some p not followed by QRS
o High grade -> when more atrial impulses fail to be conducted than are conducted.
o Mobitz type I - progressive PR interval ending by a blocked P wave (Wenckebach’s phenomenon) - usually bening and does not require treatment
o Mobitz type II - unexpected blocked p waves. PR before and after are normal. More likely to worsen and result in clinical signs.
How can we differentiate between Mobitz I and II?
Atropine - 0.04mg/Kg IV or glycopyrrolate 0.01mg/kg IV
Mobitz I will improve.
Mobitz II unchanged or worsens.
3rd degree AV block
o Absence of conducted p waves to ventricles.
o Electrical ventricular activation depends on scape beats
o Ventricular rate normally 20-60bpm in dogs and 60-120bpm in cats.
o Myocardial fibrosis, inflammation or infiltration, potentially drug toxicity (Ca2+ channel blockers)
o In cats often associated with structural heart disease.
Atrial standstill
o Lack of visible atrial activity on EKG
o Temporary or persistent - persistent is rare.
o Persistent - English Springer Spaniels, predisposed to developing AV block. Young dogs. genetic etiology. Long term prognosis guarded.
o Hyperkalemia most common cause
* First change is narrowing and taller T wave
* Decrease HR with reduced p amplitude and WRS widening
* Undetectable p waves
AV blocks medical treatment
o Parasympathicolytic meds (atropine / glycopyrrolate)
o Dopamine / dobutamine - increased HR and systolic function. Indicated in B blocker overdose
o Isoproterenol (pure B agonist) - improves conduction in AV node. Given as CRI.
o Terbutaline / aminophylline - mild chronotropic effects, can temporarily increase HR in dogs with SSS.
Pacemaker therapy
o Transcuteanous pacing -> in emergency situations, painful, only under general anesthesia.
o Temporary transvenous pacing -> lead in R side of heart connected to a generator external to the patient. Can be done under sedation.
* Can be used as stabilization until permanent pacemaker improving patient stability.
* Can be used to support patients with transient bradycardia (diltiazem toxicity)
Definition of tachyarrhythmias
o Rapid cardiac rhythm that originate t¡in the atria or AV junction (about bundle of His)
o Or, it involves the atria or AV junction as critical component of a tachyarrhythmia circuit
o Classified into atrial tachyarrhythmias or AV node dependent tachyarrhythmias - helps guide therapy.
How can we differentiate DCM from tachycardia-induced cardiomyopathy?
We cannot. Once treatment is started, tachycardia-induced cardiomyopathy can be partially or completely reversed.
T/F - A narrow QRS complex will almost always be an SVT
TRUE
T/F - It is very challenging to differentiate a ventricular arrhythmia from a SVT with BBB
TRUE
How can we try to differentiate ventricular arrhythmia from SVT +/- BBB
o Identification of p waves -> if there are p waves related to QRS, indicative of SVT with aberration.
o QRS fusion completes -> hallmark of ventricular tachyarrhythmia
o If tachycardia terminates with vagal maneuvers -> supraventricular in origin. If not, it can be both.
o If tachycardia ends with administration of lidocaine -> most likely ventricular in origin.
What is an irregularly irregular SVT with no organized atrial activity seen?
Afib
Steps to differentiate atrial vs AV node regular SVT
o If an SVT continues despite AV block - atrial in origin
o If a VPC terminates the SVT - more likely that is AV node dependent
o if vagal maneuver terminates the SVT - more likely AV node.
How can we do a vagal maneuver in a small animal
o Carotid sinus massage
o Sustained, gentle compression applied for 5-10 seconds over the carotid sinus -> immediately caudal to the dorsal aspect of the larynx.
Which cardiac drugs can we use that will act on the SA node?
B-blockers
Ca channel blockers
Digitalis
Class III (amiodarone, stall)
Which cardiac drugs can we use that will act on the AV node?
Main ones:
B blockers
Ca channel blockers
Digitalis glycosides
Others that can be used:
Class IC
Class III
Adenosine
Which cardiac drugs can we use that will act on the atrial myocardium?
Class IA
Class IC
Class III
Which cardiac drugs can we use that will act on accessory pathways?
Class IA
Class IC
Class III
Comparing diltiazem, esmolol and adenosine slowing down the AV node conduction, which one is more effective?
Diltiazem - slowed AV node conduction while maintaining good hemodynamic parameters.
Esmolol - caused severe drop in LV contractility
Adenosine at 2mg/kg was ineffective.
Explain the terms
Inotropy
Chronotropy
Dromotropy
Lusitropy
Inotropy - contractility
Chronotropy - rate
Dromotropy - conduction
Lusitropy - relaxation
Consequences of Ca2+ channel blockers
Hypotension
Negative chronotropy
Negative dromotropy
Negative isotropy
Impared insulin release
Effects on peripheral vasculature, cardiac muscle and pancreatic B cells -> can lead to hemodynamic collapse with high doses.
Effects of antiarrhythmics on ventricular action potential curves
T/F - A precordial thump can be used to convert an SVT to sinus rhythm but has a low rate of success
TRUE
T/F - The need to differentiate between SV and V tachycardia is less important when direct current cardio version is used
TRUE
T/F - DC cardio version and overdrive pacing (temporary transveous pacing) are effective in terminating SVT caused by abnormal automaticity rather than reentry
FALSE - they are effective in terminating reentries rather than abnormal automaticity
How many drugs are normally used to treat atrial tachyarrhythmias long term?
2
One to decrease conduction through AV node
Second to terminate the atrial tachyarrhythmia itself.
AV node dependent tachyarrhythmias will sometimes respond to single-agent therapy aimed at slowing AV nodal conduction
Summary of sites of action of antiarrhythmics
Orthodromic vs antidromic meaning
Orthodromic impulse -> conduction in normal direction
Antidromic impulse -> conduction opposite of the normal direction.
T/F - The ventricular rate is almost never slowed adequately with only digoxin and other drugs must be added
TRUE
Why would we chose diltiazem over verapamil
Because diltiazem has a more favorable hemodynamic profile at effective anti arrhythmic doses.
T/F - Atenolol is a B blocker. Because it has negative inotropic effects, the dosages required to significantly decrease AV nodal conduction are often not well tolerated by animals with ventricular systolic dysfunction
TRUE
T/F - Class I anti arrhythmic drugs block fast Na channels and thus suppress abnormal automaticity and slow myocardial conduction velocity.
TRUE
T/F Class III antiarrhythmics are used to prolong the effective refractory period of atrial myocardium and accessory pathways
TRUE
Another option to treat certain SVTs if not medically?
Catheter ablation
3 mechanisms of ventricular tachycardia
T/F - Non-sustained VT is when it lasts < 1min
FALSE - when it lasts < 30sec
Define ventricular tachycardia
o Broad QRS tachycardia with complexes wider than 0.06sec in dogs and 0.04sec in cats.
o Each QRS complex is followed by a large T wave directed opposite to the QRS deflection
What is more common in SA, ventricular tachycardia or SVT with broad QRS (due to BBB)
VT
What are the most reliable diagnostic criteria for VT?
AV dissociation
Fusion beats
Capture beats
What is AV dissociation?
P waves are occasionally seen on the ECG tracing but are not related to ventricular complexes
Fusion beats
Result from the summation of a ventricular impulse and a simultaneous supra ventricular impulse resulting in a QRS complex of intermediate morphology and proceeded by a p wave (unless concurrent afib)
Capture beat
Supraventricular impulse conducting through the normal conduction pathways to the ventricle during an episode of VT or AIVR
Non cardiac causes of VT
Hypoxemia
AB and electrolyte disturbances - hypokalemia most important
Sympathetic stimulation
Drugs
How can affect hypokalemia when a patient is on digoxin?
Digoxin competes with K on its receptors -> hypoK increases risk of digoxin toxicity
Why can hypomagnesemia cause arrhythmias?
Mg is necessary for proper functioning (activation) of the Na/K ATPase pump
Cardiac causes of VT
Cardiac tumors (w or w/o cardiac tamponade)
Myocarditis
Endocarditis
Ischemia
DCM
ARVC
Severe SAS and PS
Cats - idiopathic HCM and concentric hypertrophy secondary to hypertension/hyperthyroidism.
Prevalence of ventricular arrhythmias in dogs with DCM
21% in a pool of breeds
16% in Newfoundlands
92% in Doberman
How is the cardiomyopathy for boxers known? Characteristics?
o Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
o Adult onset disease
o Occasional VPCs
o Overt VT associated with exercise intolerance and collapse
o Sometimes myocardial failure can be observed
o Sometimes ventricular ectopics have a LBBB morphology, indicating their right side origin.
Decision to treat on VT
o Sustained ( >30sec )
o Polymorphic complexes
o HR > 180-200bpm
o R-on-T phenomenon
Antiarrhythmics for VT
o Lidocaine - max of 8mg/kg due to neurotoxic effects. In cats, B blockers preferred.
o Procainamide - for VT that do not respond to lidocaine. Rapid IV -> hypotension.
o B-blockers - esmolol CRI can help with VT associated w/ pheochromocytoma or thyrotoxic disease in cats.
o Sotalol - main anti arrhythmic for long-term management of VT especially in Boxers with ARVC.
o Amiodarone - anaphylaxis-like reactions can occur
o Mg2+ sulfate
Starling forces equation
What does the membrane osmotic reflection coeficient in Starling’s equation means
How easy it is for albumin to move from the capillaries to interstitium
What does the water conductivity of the capillary wall in Starling’s equation means
How easy it is for water to move from capillaries to interstitium
T/F If experimentally we increase interstitial pressure, we would expect increased filtration. Studies showed there was NOT increased filtration
TRUE
What else could be affecting capillary filtration rate other than the starling forces?
Glycocalyx
Glycocalyx structure
o Complex gel between plasma and endothelium forming an endothelial surface layer
o Mostly glycoproteins and proteoglycans
o Thickness varies between 0.1 to 1um
o It is inert and has plasma proteins that get bound to it
Physiologic roles of glycocalyx
o Regulates permeability
o Influences blood cell-vessel interactions
o Affects rheology
o Controls microenvironment
Glycocalyx as a sieve
o Has a net negative charge that is depending on GAG side chain sulfation and it is affected by physiologic/pathophysiologic stimulation
o Charged mesh acts as a sieve - repels negatively charged molecules, RBCs and WBCs and molecules >70kDa
o Albumin can enter the glycocalyx and enter it due to its amphoteric nature -> reduces water conductivity across endothelium.
Revised Starling principle equation
o Now instead of oncotic pressure of interstitial space, we replace if for oncotic pressure of subglycocalyx space, that is much lower.
o Subglycocalyx is almost protein free, oncotic pressure much lower compared to interstitium.
o The membrane osmotic reflection coefficient now it has to be that of the glycocalyx rather than the endothelium.
Difference between Starling and the new revised Starling principle in terms of fluid movement
o Interstitial oncotic pressure replaced for subglycocalyx oncotic pressure
o Instead of having filtration at the pre-capillary arterioles and absorption at the post-capillary venules, we have NO absorption at the post-capillary venules, just les filtration
Effect of Starling forces and revised version on fluid flux (graphs)
Which factors do affect the Frank Starling curve
Inotrpy (contractility) and afterload
Not the preload as preload is basically the x axis
Difference between Starling graph and cardiac function?
Instead of LVEDV on x axis, we have the R atrial pressures (basically CVP)
On Y axis the CO in L/min (Frank Starling curve can have CO (L/min) or stroke volume (mL) on the Y axis)
What factors can affect cardiac function curves?
Same as FS, inotropy and afterload
Not preload as it is the x axis of the graph
Why can RA pressure reaches negative values in cardiac function curves?
Because in a patient breathing spontaneously -> negative intrathoracic pressures that will lead to negative RA pressures
What is the independent variable in the venous return curve?
Cardiac output. It is depicted on the Y axis to be able to superimpose the cardiac function curves
Why does the CO decreases as the RA pressure decreases in the venous return curves?
Because blood is being drawn into the ventricle with each beat of the heart and moved into the arterial system, leading to a drop in atrial (and venous) pressure.
Why when the RA reaches 0mmHg the CO does not change in the venous return curves?
Because at <0mmHg of the RA, the vena cava collapses, limiting venous return therefore CO plateaus.
What happens when we reach a CO of 0, for example on a CPA patient, with the RA pressure?
o Aortic pressure falls and right atrial pressure increases as blood redistributes between the arterial and venous systems until they reach the same pressure.
o Since there is no flow, the pressures in the entire circulatory system will be equal.
o This is called the mean circulatory filling pressure and in healthy animals is about 8mmHg
Explain why mean circulatory filling pressure is not the simply the difference between arterial and venous systems?
Because the venous system has a higher capacitance, it will accommodate between 10-20% more volume than arteries when CO is zero
What factors can affect the venous return curve to shift?
Intravascular volume and venous compliance
Why does the mean circulatory filling pressure changes when the intravascular volume or venous system compliance changes?
o With an increased in volume, the mean filling pressure will increase because there is greater volume in the circuit.
o Since the mean vascular filling pressure is more affected by the high compliance of the venous system than the low compliance of the arterial system, it will shift to a higher value when venous compliance decreases (ie, the veins become stiffer).
What is the independent variable in the cardiac function curve?
The RA pressure
Normal pressures on heart chambers
RA - mean of 0-5mmHg
RV - systolic of 15-30mmHg, diastolic of 0-5mmHg
LA - mean of 4-12mmHg
LV - systolic of 90-150mmHg, diastolic of 4-12mmHg
Aorta - systolic 90-150mmHg, diastolic 60-100mmHg, mean 70-100mmHg.
What is the end diastolic pressure volume relationship of the LV and how can it be generated experimentally?
o It’s the LV pressure generated by a set volume of blood within the ventricle when the ventricle is relaxed and not contracting
o You would inject blood into an isolated ventricle and record the pressure in the heart resulting from each volume.
What is the end systolic LV pressure volume relationship?
o It’s the pressure generated in the ventricle when a range of volumes are present in the ventricle.
o In this case, the ventricle is maximally contracting (at the end of systole).
o The curve is significantly higher and shifted to the left.
Myocardial perfusion pressure
MPP = Diastolic aortic pressure – right atrial pressure
Static markers of volume status
HR, MM, CRT, mental status, temperature, pulse quality, lactate, SI, MAP, CVP
- CVP considered no longer clinically valuable
Dynamic markers of volume status?
CO monitoring (thermodilution, LiDCO),
Surrogates for CO - pulse pressure variation, systolic pressure variation, stroke volume variation
Hemostasis vs thrombosis
Hemostasis is a physiological phenomenon that leads to blood clot formation.
Thrombosis is a pathological hemostasis leading to occlusion of blood supply and ischemia
Thrombus vs Thrombo-emboli
Thrombus -> aggregation of PLT and fibrin with entrapped blood cells
Thrombo-emboli -> migration of the thrombus
Virchow’s triad
Blood stasis
Hypercoagulability
Endothelial damage
Venous vs arterial thrombi
o Venous thrombi -> created under low shear stress rates -> fibrin generation plays a major role.
o Venous thrombus is primarily composed of RBCs embedded within a fibrin meshwork.
o Arterial thrombosis -> high shear stress conditions predominate -> PLT adhesion to endothelium is the most important part of thrombus formation.
o Arterial thrombus is primarily composed of PLT.
Signalment of ATE cats
o Between 7-12yo
o Males predisposed -> 2/3 of cases are males
o 75% of cases have both limbs affected.
o 90% have underlying cardiomyopathy but <10% were previously diagnosed w/ cardiac dz.
T/F - Cats with cardiac disease have higher median fibrinogen concentration compared to healthy cats
TRUE
Hypercoagulability has been found in ______% of cardiomyopathies cats with spontaneous echocardiographic contrast (SEC)
50%
Causes of blood stasis
Reduced blood velocity
Reduced or turbulent flow (often caused by vascular, valves or chambers abnormalities)
Endothelial injury is difficult to diagnose in vivo. It revolves around increased ________ __________ and increased concentration of ________ __________ _________
Platelet activation
Activated clotting factors
The “5P” rule to diagnose FATE
o Mostly clinical
o Palor (purple or pale toes)
o Polar (cold extremities)
o Pulselessness
o Paralysis
o Pain
Other tools that we can use to diagnose a saddle thrombus?
o Glucose/lactate differential between the affected limb and normal limbs - glucose lower and lactate higher in affected limbs compared to the normal ones.
o BLASTT study - lactate might be a more robust diagnostic tool compared to glucose.
o The use of infrared thermography used in 16 cats to differentiate FATE from non-ischemic conditions, a 2.4C difference was wound between ipsilateral affected and non-affected limbs.
o Infrared thermography had a sensitivity of 85%, specificity of 100%, PPV of 100% and a NPV of 80% to diagnose ATE as cause of paralysis. Can also be used to assess repercussion of affected limbs.
When ATE is treated, survival?
Between 27-45%
BLASTT study, prospective randomized study comparing thrombolysis with tPA or placebo had a discharge of ______ for bilateral FATE
35%
T/F Cats with motor function at admission, or one limb affected have a better prognosis (70% survival to discharge) than cats with bilateral pelvic paralysis (25% survival to discharge)
TRUE
Do the CURATIVE guidelines recommend treatment with thromboprophylaxis for FATE patients?
Yes
Do the CURATIVE guidelines differentiate in hospital treatment vs prevention for FATE survivors vs prevention for high FATE-risk patients?
No
What are the CURATIVE thromboprophylactic recommendations for FATE patients?
o The use of clopidogrel, UF or LMWH
o Clopidogrel at 18.75mg PO SID. Loading dose suggested to obtain therapeutic plasma concentrations rapidly.
o If using heparin, initial SQ dosage of UFH of 250U/kg QID or dalteparin 75 U/kg QID
o Enoxaparin 0.75-1mg/kg SQ BID to QID for cats at risk for venous thromboembolism but no specific recommendations for LMWH.
T/F CURATIVE guidelines recommend in favor of aspirin as the sole antithrombotic in cats with FATE
FALSE - they recommend against aspirin as the sole antithrombotic and do NOT recommend an appropriate dosage in cats.
Why CURATIVE do not recommend warfarin for FATE cats?
They suggest warfarin not to be used because of marked inter-individual variation coupled with a narrow therapeutic index.
What do CURATIVE recommend recording rivaroxaban in cats with FATE?
o Appears safe and well tolerated.
o Dose of 0.5-1mg/kg/day recommended in cats.
What is the only FDA approved thrombolytic drug in the USA?
t-PA
Has it been used? What is the main concern?
o Yes
o Results have been mixed
o Repercussion injury - cats after receiving t-PA developed hyperK, neurological sings leading to respiratory arrest and hemorrhagic complications in one study.
Percentage of FATE cats with concurrent CHF
44-67%
Treatment of FATE
o Furosemide 1-2mg/kg until resolution of pulmonary signs
o 2% nitroglycerine crea for potential ventilatory effect
o +/- sedation with butorphanol or methane of pain.
o FATE is painful, recommended full mu opioids with methadone followed by fentanyl CRI
o Physical therapy with PROM and leg warming can be attempted if tolerated by the patient
Is it very common canine thrombosis (CATh)?
No
Processes that have been implicated in CATh
o PLN
o Cushing’s
o DM
o Hypothyroidism
o Liver disease
o Neoplasia
o Infective endocarditis
o Immune mediated diseases requiring high steroid doses (IMHA, ITP, Addison’s)
How is normally CATh diagnosed?
o Visualization of the thrombus in the aorta on ultrasound
o Glucose differential has been used in 1 study - a difference of >30mg/dL corresponded to 100% sensitivity and specificity.
Prognosis of CATh
o Varies based on presentation and clinical signs
o In the largest case series published - discharge rate of 57% and 63% with severe enough clinical signs to be hospitalized.
CURATIVE guidelines recommendations for dogs with CATh
Suggest that antiplatelets might be more effective than anticoagulants for prevention of CATh, but anticoagulants may also be effective for prevention.
CO - units and normal values for dogs and cats
mL/kg/min or mL/kg/m2
Dogs - 100-150
Cats 80-130
Explain the Fick principle for cardiac output
Fick principle states that blood flow to an organ can be calculated using a marker substance if the following information is known:
Amount of marker substance taken up by the organ per unit time
Concentration of marker substance in arterial blood supplying the organ
Concentration of marker substance in venous blood leaving the organ
How can we use the Fick principle with CO2 production?
o CO2 clearance is another marker to determine CO
o Can be performed “non-invasively” through the NICO (rebreathing) system (non-invasive cardiac output)
o Measurement of ETCO2 to determine arterial CO2 (ETCO2N = CaO2)
o Use of partial rebreathing ETCO2 for mixed venous CO2 (ETCO2R = CvCO2)
o Measurement of CO2 expired (produced) (VO2)
o CO = ΔVO2 / (S * ΔETCO2)
What are the indicator dilution techniques?
They involve the injection of a known volume of fluid (V1) with a known concentration of an indicator (C1) into an unknown larger volume (V2) and then measuring the concentration of the indicator in the larger volume of fluid (C2). The unknown volume (V2) can be calculated:
V1 x C1 = V2 x C2
What are valid indicators?
Any indicator can be used as long as it can be measured with a rapidly responding sensor.
What is the indicator in thermodilution methods? Explain
o Temperature
o It involves measurement of temperature at two distinct locations
o Pulmonary artery catheter - Swan-Ganz catheter
o Injection of cold saline in proximal port, temperature measured at the tip of the PAC
o Multiple dilutions performed, average for each CO
o Thermistor tip can allow continuous CO monitor
o Can be also used to assess PCWP (LA pressures) and obtain samples for SvO2
Thermodilution - accuracy and complications
o Accuracy and reliability questioned
o Can be affected by blood temperature, concurrent fluid administration and sample handling
o Inaccuracy with valvular regurgitation (blood not mixed completely due to regurg) and anatomical shunts
o Potential complications: pneumothorax, infection, bleeding, clot/PTE
o Limited use in vet med due to cost, availability and potential complications
Indicator dilution - LiDCO
o Injecting lithium chloride
o Peripherally or centrally, IV bolus - it stays in the intravascular compartment
o Ion selective electrode attached to arterial line
o CO computed
o CO = (Indicator dose x 60) / total dose x (1-PCV)
o Need to measure Na and PCV before each dilution
o Validated in multiple veterinary species
o Lithium accumulation with repeated measurements - background interferences, potential toxicity
o Volume of blood withdrawn may limit repeated measures
Pulse contour analysis
o Correlate arterial blood pressure tracing AUC to stroke volume
o Potential limitations
* Non-linear relationship between pressure and volume (effect of arterial compliance, resistance…)
* Damping of the pressure waveform (arterial catheter, fluid tubing, pressure transducer)
% of CO that goes to different organs
Sepsis is usually associated with normal or high CO, despite myocardial depression. Why?
o The pathophysiology of sepsis involves the release of cytokines, some of which are associated with abnormal calcium handling by the cardiac myocytes, leading to reduced myocardial contraction.
o Because of the simultaneous tachycardia and reduced vascular tone, however, afterload is reduced – and cardiac output can therefore be maintained or even increased. “
The two classic pathways involved in the genesis of heart failure
RAAS and SNS.
The natriuretic peptides, endothelin, and vasopressin systems also play a role.
List maladaptive responses where AGII is involved, that promote further cardiac injury in patients with heart failure
o Renal sodium and water retention
o Production of aldosterone
o Myocardial apoptosis
o Cardiac and vascular remodeling and fibrosis
o Increased thirst
o Vasoconstriction
T/F Angiotensin II can be generated from pathways independent of ACE and elevations of angiotensin II and aldosterone that can occur in spite of ACE inhibitor therapy.
TRUE
The _____________ serves as a counterregulatory system to the RAAS and SNS
Natriuretic system
Myocardial tissue produces two main hormones that induce natriuresis, diuresis, and vasodilation
o Atrial natriuretic peptide (ANP)
o B-type natriuretic peptide (BNP)
In later stages of heart disease, the beneficial activity of the natriuretic peptide system is overwhelmed, resulting in the clinical appearance of CHF. Why?
o Natriuretic peptide receptor downregulation
o Inappropriate or inadequate production or processing of the peptides
o Increased peptide clearance or degradation
_________________ is a potent vasoconstrictor produced by vascular endothelial cells in response to sheer stress, angiotensin II, and other various cytokines, causes increased cardiac afterload.
o Alters normal calcium cycling within muscle cells and is directly toxic to myocardiocytes
o Is elevated in dogs and cats with heart failure
Endothelin 1
Define dilutional hyponatremia and it’s prognostic utility in CHF
o Indicates heightened free water retention to the extent that serum sodium concentrations are decreased, despite an overall excess of body-wide sodium.
o In both humans and veterinary patients, dilutional hyponatremia is a marker of severe neurohormonal activation and is a poor prognostic sign.
Describe concentric hypertrophy, conditions associated and consequences
o Is a response to conditions causing pressure overload (i.e., increased afterload), as in the case of systemic hypertension or subaortic stenosis.
o Increased afterload triggers replication of sarcomeres in parallel -> increase in the relative thickness of the ventricular walls.
o Consequences -> increased myocardial oxygen demand, endocardial ischemia, fibrosis, collagen disruption, and injury to small coronary vessels.
Describe eccentric hypertrophy, conditions associated and consequences
o In instances of volume overload, such as mitral regurgitation or dilated cardiomyopathy.
o Sarcomeres replicate in series leading to elongation of myocytes and dilation of the ventricular chamber.
o The limitations of concentric hypertrophy include increased myocardial wall stress, myocyte injury or necrosis, and myocyte slippage.
Describe abnormalities of myocyte calcium ion cycling in patients with heart failure
As its main substrate for energy production, the heart can utilize: ____________. • In heart failure, the heart preferentially uses ________________
Glucose and free fatty acids
Glucose -> requires less oxygen than fatty acids
Draw the Frank Starling relashipnship of CO and preload curve and show how it is shifted during increased adrenergic drive in health (ex. Exercise), and during low-output heart failure. How diuretics, positive inotropes and vasodilators affect the curve?
o Arterial vasodilators (amlodipine or hydralazine) -> shift the curve upward in a manner similar to a positive inotrope.
o Venous vasodilators (nitrates) -> reduce preload through an increase the capacitance of the venous system and shift the curve leftward, similar to diuretics.
o Mixed vasodilators (ACE inhibitors) result in a combination of both upward and leftward adjustment”
Classic example of diastolic heart disease is
HCM in cats
Diastolic heart disease can be due to
o Primary impairments of ventricular relaxation, filling or compliance
o Secondary to disease of the pericardium
Ventricular compliance is affected by
o Thickness of the ventricular wall (concentric hypertrophy)
o Changes in the cytoskeleton and extracellular matrix (fibrosis)
o Function of the pericardium (pericardial disease or effusion)
T/F In the early phase of diastole, relaxation requires energy as the movement of calcium ions back into the SR operates using ATP-driven pumps
TRUE - SERCA is an ATPase pump.
o Then, in myocardial ischemia and energy deficit, active relaxation is delayed and early filling of the ventricle is diminished.
T/F Positive inotropes play little role in the management of diastolic dysfunction
TRUE - In the absence of obvious pericardial disease, treatment focuses on increasing the time available for diastolic filling by decreasing heart rate, suppression of arrhythmias, and alleviation of congestion through the use of diuretics and vasodilators.
Describe the clinical staging of heart failure
Class A
o Overtly healthy animals that are at risk for developing heart disease.
o Doberman Pinschers over the age of 4 or adult Maine Coon cats.
o Might benefit from screening programs to detect the possible onset of disease
Class B
o Diagnostic evidence of heart disease but without clinical signs
o ex. Dogs with a murmur, cats with arrhythmias
o B1 - no radiographic or echocardiographic evidence of cardiac remodeling, as well as those in which remodeling changes are present, but not severe enough to meet current clinical trial criteria used to determine that initiating treatment is warranted
o B2 - with radiographic or echocardiographic evidence of cardiac remodeling, that meet clinical trial criteria used to identify dogs that clearly should benefit from initiating pharmacologic treatment to delay the onset of heart failure
Class C
o With cardiac remodeling, as well as current or historical clinical signs of heart failure
Class D
o Patients with severe and debilitating signs of heart failure even at rest. clinical signs of heart failure are refractory to standard treatment.
Pulmonary venous pressures greater than ___________ and systemic venous pressures greater than ___________are sufficient to produce congestion that manifests as pulmonary edema, pleural effusion, or ascites.
25mmHg
20mmHg
How does low output heart failure develops and what are classical clinical signs
o In patients with severe myocardial dysfunction, cardiac performance is insufficient to provide adequate cardiac output and animals present with signs of low-output heart failure.
o Common clinical signs include weakness, depressed mentation, cardiac shock, and syncope.
o Diagnostic testing in these patients commonly reveals hypothermia, hypotension, azotemia, anuria or oliguria, and lactic acidosis. Patients with low-output heart failure require positive ino tropes to improve contractility”
List causes of L sided heart failure in dogs and cats
Common causes of left-sided heart failure in dogs:
o Degenerative mitral valve disease
o Dilated cardiomyopathy
o Patent ductus arteriosus
Common causes of left-sided heart failure in cats:
o HCM
o Restrictive cardiomyopathy”
List causes of right sided heart failure in dogs
o Dilated cardiomyopathy
o Degenerative or congenital tricuspid valve disease
o Pulmonary hypertension. “
T/F in the cat, pleural effusion can occur as a result of either left- or right-sided heart failure
TRUE
T/F Ascites as a sign of right- sided heart failure in cats is common
FALSE - Ascites as a sign of right- sided heart failure in cats is relatively uncommon, and most cats with ascites are afflicted with noncardiac diseases
Right-sided heart failure is relatively rare in cats and most cases of cardiogenic pleural effusion in cats actually are due to left-sided disease.
In the face of adequate intravascular volume, but reduced cardiac output from cardiac dysfunction, a patient has__________
Forward flow failure
Describe backward and forward flow failure, give examples
o Backward flow failure -> secondary to elevated venous pressures
o Forward flow failure (left ventricular failure) -> reduced forward flow into the aorta and systemic circulation
• Most patients deteriorate secondary to the increase in preload and subsequent congestive (backward) heart failure and pulmonary edema
• Some patients may suffer from concurrent forward and backward failure (e.g., dogs with dilated cardiomyopathy).”
T/F The heart rate should be elevated in animals with cardiogenic shock unless a primary bradyarrhythmia is the cause of the cardiogenic shock or the patient is moribund
TRUE
Radiographic signs of CHF include:
o Enlarged pulmonary veins
o An alveolar or interstitial pattern in the perihilar region (in dogs only; infiltrates are often patchy or diffuse in cats)
o Pleural effusion
In L-CHF
* Increased VHS
* Dorsal displacement of trachea due to LA enlargement
R-sided disease
* Reverse D cardiac sillhouette
* Increased sternal contact
* Enlarged CVC
* Ascites
List causes of systolic dysfunction
- A decrease in cardiac contractility
* DCM
* ARVC
* Sepsis
* Endomyocarditis
* Myocardial infarction - Decreased flow through the left ventricular outflow tract (mechanical failure).
*Functional obstruction (e.g., aortic stenosis or hypertrophic obstructive cardiomyopathy)
* Severe retrograde blood flow (e.g., chordae tendineae rupture and acute, severe mitral regurgitation)”
Pathophysiology of DCM
o Progressive decrease in myocardial contractility that occurs over months to years -> gradual decrease in stroke volume and forward failure -> activation of the RAAS system and SNS -> increased intravascular volume -> increased end-diastolic volume -> eccentric hypertrophy secondary to cardiac myocardial stretch.
o Compensatory mechanisms will maintain cardiac output until the myocardial failure becomes so severe that the cardiac chambers cannot sustain further enlargement -> increase in pulmonary capillary hydrostatic pressure and cardiogenic pulmonary edema or ascites.
o An electrocardiogram may show a sinus tachycardia or arrhythmias such as atrial fibrillation or ventricular tachycardia.
In this condition, cats have normal myocardial function before anesthesia for a routine procedure, but cardiac dysfunction, hypotension, pulmonary edema, and interstitial pneumonia rapidly develop. Although not well described, the endocardium is ____________on echocardiography, and histopathology reveals ______________. Supportive care is recommended, and even with positive pressure ventilation the prognosis is often poor
Endomyocarditis
hyperechoic
neutrophilic inflammation and fibroplasia.
List causes of diastolic dysfunction
Hypovolemia
Physical restriction. Ex: Tamponade
Inhability to relax: HCM
Inadequate time to fill: Tachycardia
The most common cause of pathologic bradyarrhytmias is
Severe high-grade second-degree AV block
In patients with third-degree AV block, what are the typical heart rates based on location of the extranodal impulses?
o Bundle of His producing 40 to 60 beats/min
o Bundle branches or distal Purkinje fibers producing 20 to 40 beats/min
o Cats with third- degree AV block typically have a higher ventricular escape rhythm of 100 to 140 beat/min and thus less commonly present for cardiogenic shock or syncope.
__________________ is caused by persistent supraventricular or ventricular tachyarrhythmias and is characterized by systolic dysfunction and ventricular dilation
Tachycardia-induced cardiomyopathy
What are the two diagnostically relevant cardiac troponins
cTnI –> rises rapidly after myocardial cell damage (myocarditis)
cTnT
T/F Furosemide will decrease the rate of future fluid accumulation; however, it has very little effect on existing pleural or abdominal fluid.
TRUE
T/F Doxorubicin toxicity is generally reversible
FALSE
Define restrictive cardiomyopathy
Occurs when there is impaired ventricular filling in the absence of myocardial hypertrophy or pericardial disease. Left atrial enlargement with normal ventricle.
What is the predominant pathophysiologic mechanism responsible for clinical signs in HCM and RCM
Diastolic dysfunction
What is the percentage of cats with HCM that develop SAM?
65%
Define/explain how SAM occurs in cats with HCM
Abnormal drag forces are responsible for systolic movement of the MV leaflets toward the septum that results in dynamic—as opposed to fixed—left ventricular outflow tract obstruction and, usually, concurrent mitral valve regurgitation
What is the most important cause of a heart murmur in cats with HCM?
SAM
Decreases in preload and afterload or increases in contractility may provoke or augment SAM, and this may explain the fact that the intensity of the associated murmur may vary from moment to moment
What is the most common site of thrombus formation in FATE
LA - specifically the appendage
What is the most common site of embolism in FATE?
Aortic trifurcation
Suspected risk factors for FATE
o Left atrial enlargement
o Echocardiographic findings of spontaneous contrast and systolic myocardial dysfunction.
T/F Long-term prognosis for cats with glucocorticoid-associated CHF may be worse than for those with CHF from more typical causes
FALSE - long-term prognosis for cats with glucocorticoid-associated CHF may be better than for those with CHF from more typical causes.
NT-BNP concentration identified respiratory distress caused by feline cardiomyopathy with high sensitivity—________%—and a somewhat lower specificity that was in the________
near 90%
high 80s
T/F - Tachypnea is a reliable clinical finding of CHF in cats with FATE
FALSE - tachypnea was identified in 89% of patients with FATE in the absence of CHF (presumably as a result of pain).
T/F - hypothermia is associated with reduced survival in FATE
TRUE - 50% short-term survival for patients with a body temperature of 37.2° C (98.9F)
MOA of Nitroglycerin
Causes venodilation as well as dilation of specific arteriolar beds, including those of the coronary circulation
MOA of Ivabradine
o Antagonist of ““funny”” lf sodium channel
o Slow heart rate but do not exert a negatively inotropic effect
The PROTECT Study has shown that administration of pimobendan to Doberman Pinschers with preclinical DCM _________________________
Prolongs the time to onset of clinical signs and extends survival
Deficiency in ________ implicates this cytoskeletal protein abnormality as one of the possible causes of DCM in Doberman Pinschers
Calstabin-2
This breed has a juvenile form of DCM
Portuguese water dog
Why NT-proBNP is used for determination of heart disease? Which other disease processes can influence NT-proBNP concentration?
Has a longer half-life in circulation and therefore is easier to measure.
Pulmonary hypertension, renal dysfunction.
Describe the treatment for a patient classified in Stage B2 of heart failure
o Pimobendan 0.25-0.3 mg/kg PO q12h.
o Mild dietary sodium restriction and provision of a highly palatable diet with adequate protein and calories for maintaining optimal body condition
o Clinical trials addressing the efficacy of ACEI for treatment of dogs in Stage B have shown mixed results - 5 (of 10) panelists recommend treatment
o Cough suppressants useful in occasional patients in advanced Stage B2 when their cough is thought to be the result of pressure from cardiac enlargement
o Surgical intervention in advanced Stage B2 is possible and recommended by some panelists.
What is the recommendation of Dobutamine use for patients with MVD in the ACVIM consensus?
In stage C patients with acute signs (hospital based treatment) in patients that fail to respond adequately to diuretics, pimobendan, sedation, oxygen, and comfort care measures
Dobutamine (2.5-10 μg/kg/min CRI, starting at 2.5 μg/kg/min and increasing the dosage incrementally)
** Continuous ECG monitoring is recommended, with dosage reduction indicated if tachycardia or ectopic beats occur
List potential causes of diuretic resistance in a stage D MVD patient
- noncompliance (not receiving the drug)
- high sodium intake, slow absorption (gut edema)
- impaired secretion into the renal tubular lumen (CKD, advanced age, concurrent NSAIDs use)
- hypoproteinemia, hypotension, nephron remodeling, and neurohormonal activation
What is a typical echocardiographic finding with cardiac tamponade?
Right atrial collapse
What are the two most common causes of hemorrhagic pericardial effusion?
Neoplastic - Idiopathic
What are uncommon causes of hemorrhagic pericardial effusion?
Left atrial rupture secondary to severe MVD - coagulopathy (rodenticide/DIC) - Trauma
Which one is the most common heart base tumor?
Chemodectoma (aortic body tumor)- arises from the chemoreceptor cells at the base of the aorta
Mention neoplastic causes of pericardial effusion other than hemangiosarcoma
Pericardial mesothelioma - cardiac lymphoma - Malignant Histiocytosis - metastatic carcinoma
Describe the characteristics of pure transudative effusion vs a modified transudate
Pure transudate = Cell count <1000/uL - SG: <1012 - TP: <2.5g/dL / Modified transudate = Cell count 1000-8000/uL - SG: 1015-1030 - TP: 2.5 - 5g/dL
Mention causes of a transudative pericardial effusion
CHF, Hypoproteinemia, vasculitis (ex. Toxicities that increase vascular permeability, uremia), congenital pericardial malformations, cardiac lymphoma in cats
Mention causes of exudative pericardial effusion
Migrating foreign body (plant awn), infection (extension of pleural or mediastinal infection, bite wound)
Mention etiology agents for infectious exudative pericardial effusion in dogs and cats
Actinomycosis, coccidiomycosis, Aspergillus, tuberculosis, systemic protozoal infections (rare)———–
Dogs = distemper, leptospirosis
Cats= FIP
Define Cardiac tamponade
When intrapericardial pressure rises toward and exceeds normal cardiac diastolic pressures
Define Pulsus paradoxus
A fall in arterial pressure during inspiration of 10 mm Hg or more
What are causes of a globoid-shaped cardiac shadow on radiographs other than massive pericardial effusion?
DCM, marked tricuspid (with or without mitral) insuficiency
Mention EKG changes seen with cardiac tamponade
o Reduced amplitude QRS complexes (less than 1 mV in dogs)
o Electrical alternans (recurring, beat-to-beat alteration in the size or configuration of the QRS complex (and sometimes T wave)
o Atrial and ventricular tachyarrhythmias occur in some cases
How does cardiac tamponade affects CVP?
Cardiac tamponade commonly produces CVP measurements of 10 to 12 cm H2O or higher
How can pH help in the classification of a pericardial effusion?
Many neoplastic (and other noninflammatory) effusions have a pH of 7.0 or greater, whereas inflammatory effusions generally have lower pH. However, there is too much overlap for pericardial effusion pH to be a reliable discriminator.
Which is the preferred side to perform pericardiocentesis?
Right side of the chest. This minimizes the risk of trauma to the lung (via the cardiac notch) and major coronary vessels, most of which are located on the left.
Mention the complications of pericardiocentesis
Ventricular arrhytmias, hemorrhage, myocardial injury (coronary artery laceration, myocardial infarction), infection, lung laceration, pneumothorax, diseemination of neoplasia into pleural space
What is the treatment for idiopathic pericardial effusion that does not respond to antiinflammatory therapy and repeated pericardiocentesis?
Subtotal pericardiectomy - techniques = thoracoscopy (allows biopsy or resection of small right auricular masses); thoracoscopic partial pericardectomy, percutaneous ballon pericardiotomy
Besides antimicrobial drugs, what are other treatment options for infectious pericarditis
o Pericardiocentesis prn
o Infusion of antimicrobial agents might help
o Indweling pericardial catheter
o Surgical debridement
Define constrictive pericardial disease
When thickening of the visceral or parietal pericardium impairs ventricular diastolic expansion and prevents cardiac filling
What’s the most common pericardial malformation in dogs and cats?
Peritoneopericardial diaphragmatic hernia (PPDH)
Define bradyarrhythmia
bradycardia (heart rate below than 60 beats/min in dogs, 100 beats/min in cats) associated with clinical signs, such as lethargy, decreased appetite, exercise intolerance, CHF, and syncope.
Mention extra-cardiac factor that can cause bradyarhythmias
Hypothermia, hyperkalemia, GI/ocular/neurologic/respiratory disease, Hypertension (reflex bradycardia), hypothyroidism / Iatrogenic (ABCD opioids, alpha-2 agonists, anesthetics)
Mention the conduction disturbances, which ones are not associated with clinical signs?
Bundle branch blocks, first, second and third degree AV blocks. - Bundle branch and first degree AV blocks are not associated with clinical signs
How long does the heart has to pause in order to cause syncope
6 to 8 seconds
Define sick sinus syndrome
Periods of normal sinus rhythm or sinus bradycardia intercalated with prolonged pauses that can be as long as 10 to 12 seconds because the junctional and ventricular pacemarkers fail to generate escape beats.
Which breeds are commonly affected with sick sinus syndrome
Older miniature schnauzers,Terrier breeds, Cocker Spaniel, Daschunds
Define first degree AV Block and mention possible causes
All the atrial impulses are conducted but the PR interval is prolonged - causes= increased vagal tone, fibrosis, medications that delay AV conduction (Ca channel blockers, B blockers, digoxin)
What are the two types of second degree AV block
Mobitz type I –> progressive increase in PR interval ending by a blocked P wave (alson known as Wenckebach’s phenomenom). Usually improves with atropine. Mobitz type II –> unexpected ocurrence of blocked P waves, PR intervals before and after the block are identical. Usually does not change with atropine or worsens.
Define third degree AV block
Abscense of conducted P waves to the ventricles. Atrial and vetricular activities are independent. QRS complexes depend on escape rhythm beyond the site of block
What are the usual ventricular rates in dogs and cats with a third degree AV block
QRS complexes depend on escape rhythm beyond the site of block and rates are usually 20-60bpm in dogs and 60-120bpm in cats
What is the most common cause of AV block in dogs?
age-related fibrodegenerative disease
define atrial standstill
Absent p waves with regular ventricular or AV nodal escape rhythm at rates of 20 to 60bpm in dogs.
Mention causes other than hyperkalemia for atrial standstill
o Persistent Atrial Standstill (PAS) English Springer Spaniels predisposed, genetic etiology is likely, usually afecting young dogs. Atria fail to depolarize despite normal Sinus node discharge - Generally a significant myocardial pathologic condition is present and the long-term prognosis is guarded
o Cardiac glycoside toxicity
o Hypothermia (temporary atrial standstill)
How whould you perform an atropine response test
Atropine 0.04mg/kg IV or IM with ECG trace. Repeat ECG in 15 and 30 min. –> should demostrate sinus tachycardia (~140bpm within 30min) if the bradycardia is vagally mediated.
Mention possible side effects of therapy with anticholinergic/parasympatholytic medications and how could you contrarest these effects?
o Mydriasis, dry mouth, constipation, urinary retention, neurologic signs, symptoms of poor arterial perfusion (syncope)
o Terbutaline or Theophylline can be used
If you have a patient with a bradyarrhythmia that does not respond to the atropine test and you need to consider a pacemaker placement, what are possible therapeutic options in the meantime and what are your top differentials for the bradyarrhythmia?
o Isoproterenol and dobutamine might be effective in stabilizing the patient
o Most likely diagnoses: sick sinus syndrome, third degree AV block, high grade second degree AV block.
Describe oral therapies that can be considered for management of patient with vagally mediated bradyarrhythmias?
Terbutalline, Theophilline, Hyoscynamine, propantheline –> they are rarely effective long term and are associated with significant side effects
Explain de advantages and disadvantages of using Isoproterenol in a patient with AV block
o Advantages = pure B blocker, can improve conduction in the AV node and His-Purkinje system. Can be considered if pacing is unavailable, or in B blocker or Ca channel blocker toxicities
o Disadvantages= B2 efect can cause significant decrease in dyastolic pressure, also acidosis decreases its effectiveness.
Whart is the main disadvantage of Transcutaneous pacemaker therapy
The stimulation of the local skeletal mucles can be painful, so usually is used only on anesthetized patients.
Why are the QRS complexes wider in ventricular tachycardias?
Because the myocyte to myocyte conduction is smaller than a normal conduction transmited thorugh the ventricles His-Purkinje system
List differentials for a wide QRS complex
Ventricular ectopic beat / Right axis deviation due to right ventricular enlargement or cardiac displacement / hyperkalemia / Bunddle branch block
Which type of bradyarrhythmia can cause sporadic seizure like clinical signs in cats?
High grade second degree AVB lacking sufficient escape activity
Describe the technique of temporary transvenous pacing therapy
A lead is placed in the right side of the heart, usually the right ventricle - Jugular, spahenous or femoral vein can be used, fluoroscopy guidance is recommended - a HR rate is programed to 80-100 bpm - can be done in awake or mildly sedated patients.
Define SVT
rapid heart rhythm that: originates or involves the SA node, atrial myocardium, AV node (before the bundle of his) or great vessels conecting to the atria.
What is the presumed mechanism of sudden death in patients with SVT?
Myocardial ischemia thas gives rise to VT and fibrilation
What is the difference between dilated heart secondary to SVT (tachycardia-induced cardiomyopathy) and idiopathic DCM?
SVT can be partially or completely reversible
How can you distinguish an SVT from a ventricular tachyarrhythmia on ECG?
A narrow QRS complex tachyarrhythmia will almost always be an SVT / The vast majority of wide complex tachyarrhythmias are ventricular tachyarrhythmias / Identification of P′ waves with a consistent relationship to the QRS is indicative of an SVT / QRS fusion complexes are a hallmark of ventricular tachyarrhythmia / If the tachycardia terminates in response to a vagal maneuver, this indicates that the tachycardia is supraventricular in origin. /If the tachycardia does not terminate with a vagal maneuver, it may be of either supraventricular or ventricular origin./ If the tachycardia terminates with the administration of IV lidocaine, the wide complex tachyarrhythmia is most likely ventricular in origin. Rarely, an atrial tachycardia will convert with lidocaine therapy
When an SVT terminates in response to a vagal maneuver or a PVC terminates the SVT, what is the likely origin of the SVT?
More likely AV (not atrial)
What are the SVTs in small animals
Sinus tachycardia and atrial arrhythmias (atrial fibrilation, atrial flutter, Intra-atrial reentrant tachycardia, orthodromic AV reciprocating tachycardia, automatic atrial tachycardia, sinus node re-entranrt tachycardia, AV nodal re-entrant tachycardia, automatic junctional tachycardia)
Define physiologic AV block
When atrial activity is excesively rapid, the AV node might limit the P waves that will be conducted to the ventricles (in a 2:1 ration, being 1:1 normal). If the ratio is 3:1 it is considered a second degree AV block)
What are the treatment goals in a patient with atrial tachyarrhytmias?
Atrial tachyarrhythmias are best addressed by dual therapy: one drug to slow AV nodal conduction and a second drug to inhibit the atrial automatic focus or interrupt conduction in an atrial reentrant circuit.
What is the purpose of a vagal maneuver?
First approach in an animal with tachycardia –> the goal is to increase the parasympathetic tone to the SA and AV nodes
Whats the most effective vagal maneuver in small animals
Carotid sinus massage -> sustained, gentle compression is applied for 5 to 10 seconds over the carotid sinus, which is located immediately caudal to the dorsal aspect of the larynx
Which drug has proven supperior efficacy in slowing AV nodal conduction while maintaining a favorable hemodynamic profile? And how whould you use it?
Diltiazem = intermitent dosing 0.125-0.35 mg/kg IV over 2 to 3 min. CRI 0.125 - 0.35mg/kg/h if frequent reocurrence
If single therapy with Diltiazem does not control and SVT in your patient, what is other alternative? What are contradindications of it?
Esmolol (ultra-short selective B1 blocker 0.5mg/kg IV over 1 to 2 min) / contraindication = patient with decreased ventricular systolic function (it can cause a severe drop in L ventricular contractility at dosages that prolong AV nodal conduction)
What are negative effects of a Ca channel blocker overdose?
negative dromothropic, inotropic and chronotropic effect, hypotension, bradycardia, impaired insulin release (acts in pancreatic B cells –> hyperglycemia)
Explain how the stimulation of B1 receptors increases HR, myocardial contractility, and myocardial relaxation
B1 receptors couple with adenyl cyclase resulting in enhanced cyclic AMP production –> HR increases due to stimulation of funny current (If) and L-type calcium channels/ Myocardial contractility increases due to L-type Ca current influx stimulating release of Ca from sarcoplasmic reticulum / Increased myocardial relaxation occurs due to phosphorilation of phospholamban
Mention effects on a patient with B blocker overdose
Bradyarrhytmias, bronchospasms, impaired contractility, impaired glycogenolysis, gluconeogenesis and lypolysis
Describe indications to perform precordial thump, and how would you do it
To convert SVT to sinus rhytm, shockable rhytms in CPR when defibirlator not available / sharp concussive blow in left precordium (patient in right lateral) –> this could cause myocardial depolarization that can disrupt a reentrant tachycardia circuit
What are treatmet option besides vagal maneuver, medical management and precordial thump for SVTs?
Direct current cardioversion / overdrive pacing / Transvenous frequency catheter ablation
Which medications can be considered as first line medical therapy for patients with SVT?
Animals with systolic dysfunction classically are placed on digoxin as a first-line negative dromotrope -> however, the ventricular rate is almost never slowed adequately and other drugs must be added -> diltiazem is effective in prolonging the effective and functional refractory periods of the AV node
What are considerations to use Atenolol in the treatment of SVTs in dogs and cats?
o B1 selective blocker –> because of its negative inotropic effects, the dosages required to significantly affect AV nodal conduction are often not well tolerated by animals with ventricular systolic dysfunction.
o Is particularly useful in cats with hypertrophic cardiomyopathy and SVTs
What are disadvantages of using procainamine as a long term therapy medication?
Frequent dosing needed (2 to 4h), GI effects, proarrhythmic properties
What are the most common non-cardiac causes of VT?
Hypoxia, acid-base disturbances, electrolyte disturbances, drugs
Define VT in cats
occurrence of 4 or more VPCs in a row and a HR of 240 or more
What are the most common cardiac causes of VT?
ARVC in boxers, DCM
Define ventricular escape rhythm or idioventricular rhythm
When the Purkinje fibers work as a pacemaker if the impulse cannot be generated or conducted in the SA or AV nodes.
What are the three arrhythmogenic mechanisms that can affect the purkinje cells or any excitable ventricular myocyte and result in VT?
Reentry / enhanced automatocity / triggered activity
Define Accelerated Idioventricular rhythm
When the ventricular rhythm is faster than the sinus rhythm but slower than VT
Define sustained VT
More than 30sec
Describe the ECG diagnosis of Vtaq
broad QRS tachycardia with complexes wider than 0.06 second in dogs and 0.04 second in cats. Each QRS complex is followed by a large T wave, directed opposite to the QRS deflection / the three most reliable diagnostic criteria of VT are: AV dissociation/fusion beats/capture beats
You have a patients with an arrhytmia where you cannot determine its origin (SV vs ventricular), how would you stabilize this patient?
Treat as Ventricular –> Managing SVT as VT is usually less dangerous than the opposite, because drugs used to stop SVT or to slow the ventricular response rate to rapid atrial impulses (i.e., calcium channel blockers and β-blockers) do not interrupt VT and worsen hypotension with their vasodilatory or negative inotropic effects
What is the most common electrolyte disturbance responsible for or contributing to VT and why?
Hypokalemia / decreases the difference in resting potential and threshold potential –> increases phase 4 depolarization, increasing spontaneous automaticity and prolonging action potential duration (cell more exitable) –> promotes arrhytmias
Which antyaerrhythmic would be specially contraindicated in a hypokalemic patient due to enhaced activity and risk of toxicity?
digoxin –> conpetes with K on its receptors
How can hypomagnesemia predispose a patient to cardiac arrhytmias?
Mg is necessary for proper functioning of the sodium-potassium ATP pump, which maintains normal intracellular potassium concentration / hypomagnesemia can contribute to ventricular arrhythmias
Which drugs can prolong QT segment and thus have a proarrhythmic effect?
Procainamide, sotalol, domperidone, cisapride, chlorpromazine, erythromycin
what is the prevalence of cardiac arrhythmias in patients with DCM?
A study –> 21% in general, but 92% in Doberman Pinschers
Mention breeds that are more prompt to suffer VT secondary to primary heart disease
Doberman pinschers (DCM), Boxers (ARVC), German Shepherds (inherited ventricular arrhythmias)
What are possible cardiac causes of VT in cats?
Idiopathic HCM and concentric HCM secondary to hypertension and hyperthyroidism
What is your treatment of choice in a patient with nonsustained VT or AIVR after any of the following: motor-behicle-related trauma, GDV, metabolic disturbances.
Supportive tx for underlying condition, no Tx specific for the arrhythmia. Those usually resolve spontaneously within 4 days.
List possible ECG indicators of an increased risk of sudden death in a patient with VT that may prompt the clinician to treat
sustained VT with a HR>180 / R on T phenomenum / polymorphic Vtaq
Can you use lidocaine as a profilactic drug for ventricular arrhytmias? Justify
No - only works on damaged myocardium
lidocaine activity is enhanced by acidosis, hyperkalemia and partially depolarized cells
What is the maximum bolus dose of Lidocaine and why?
8mg/kg/h to avoid neurologic effects
What is the preferred antyarrhytmic class for VT in cats?
B blockers
Which combination of antiarrhythmics has proven to be effective to control VT in boxers with ARVC? What is the most commonly used long term antiarrhytmic for these cases?
Mexiletine with atenolol for control
Sotalol as long term management
What is the reasoning behind using B blockers for treatment of VT ? In which disease processes could be specially indicated?
o Sympathetic activation has been implicated in the pathogenesis of ventricular arrhytmias
o Sustained VT causing hemodynamic instability can increase circulating chatecholamines and B-blockers activity may help control these arrhythmias. –> Diseases where sympathetically driven VTs can develop include = pheochromocytoma, thyrotoxic disease in cats.
Mention indications in dogs and cats for permanent pacing
Dogs = bradycardias associated with clinical signs or high degree second AV block or third degree AV block
Cats: Severe refractory clinical signs secondary to a pathologic arrhythmia (they generaly tolerate well AVB without treatment, regardless of structural disease or CHF being present)
Mention additional treatment options beside antiarrhythmic agents for management of patients with VT
Anesthesia/sedation = decreases high sympathetic output –> benzodiazepines or propofol are used in humans / electrical therapies –> rapid pacing/synchronized electrical cardioversion
Transesophageal pacing is only useful in _________ dysfunction, but not in patients with ______ disease. This is because the system only paces consistently the ________ and not the ___________
Sinus nodal
AV nodal
Atria
ventricles
*the pacing lead is located dorsal to the heart
the three modes of cardiac pacing are:
Transvenous
Transcutaneous
Transesophageal
Indications for defibrillation
V fib
Pulseless Vtaq
Rapid polymorphic Vtaq
Shock delivery during cardioversion should be synchronized with the ___ wave of the ECG. Why?
R wave
The R wave is the absolute refractory period of the myocytes. This mode prevents delivery of a shock around the peak of the T wave, which represents the vulnerable period of the ventricles. Delivery of a shock during the vulnerable period increases the risk of initiating ventricular fibrillation because the electrical impulse reaches the ventricles during their repolarization phase, which is characterized by tissue heterogeneity.
Indications for electrical cardioversion
SVT or monomorphic ventricular tachyarrhythmias refractory to antiarrhythmic drug therapy
Which arrhythmias do not respond to electrical cardioversion?
Vfib
very irregular and rapid polymorphic Vtaq
The success of a shock terminating an arrhythmia depends on:
Amount of energy delivered
Thoracic impedance
Path of the current relative to the position of the heart
This current is the only one that reliably terminates Vfib
Direct current
What is the difference between monophasic and biphasic shock waveforms?
Monophasic defibrillators generate a uni- directional flow of current through the heart. Conversely, biphasic shocks are characterized by an initial positive current flow followed by a negative current flow in the opposite direction. These waveforms have been shown to be more effective than the monophasic configu- ration in terminating ventricular fibrillation at a lower energy setting, which may also decrease the severity of myocardial damage. Indeed, it appears that the second wave of current eliminates charges from cells that were only partially depolarized by the first phase of the shock and “heals” cell membranes damaged by the first wave of current
If Vfib is detected within the first ______ minutes of CPA, defibrilation can be performed without an initial cycle of chest compressions
4min
Pediatric paddles for defibrillation are recommended for animals that weight < than:
15kg
Cardioversion generally requires lower energy than defibrillation. The first shock is usually delivered at a level of _____ J/kg. Subsequent shocks are delivered at higher output until conversion occurs or maximum energy output fails to terminate the arrhythmia
1 to 2J/Kg
T/F - It has been suggested that the presence of structural cardiac disease does not increase significantly the energy required for cardioversion
TRUE
What is the main complication of electrical cardioversion and how would you treat it?
o The main complication of cardioversion is induction of ventricular fibrillation if the shock is not synchronized to the R wave.
o Ventricular fibrillation should be treated rapidly with a high-energy asynchronous shock.
What’s the virus “most commonly” associated with viral myocarditis? What are the least common ones?
Parvovirus (still rare) - Distemper (experimental infections) - West Nile virus (1 report in a wolf)
What’s the microorganism that causes Chagas disease?
Trypanosoma cruzi
Describe the two syndromes caused by Chaga’s disease in dogs
Acute syndrome = sudden right sided CHF, circulating trypomastigotes may be seen in circulation / Chronic syndrome = free of clinical signs for months or years, Nervous system damage: atazia and weakness.
Mention etiology agents for bacterial endocarditis
Streptococcus and staphylococcus (most common) - Lyme disease (Borrelia burgdorferi), rickettsial organisms (Erlichia canis, Rocky mountain spotted fever (Rickettsia ricketsii)), Bartonella.
Mention non infectious causes or myocarditis
Doxorubicin treatment (usually cumulative doses >250mg/m2) - vasculitis - Heat stroke - Radiation - Immune mediated polymyositis - catecholamine toxicity
Why is it recommended to use Digoxin with caution in myocarditis patients?
Digoxin increased expression of proinflammatory cytokines and increased mortality in experimental myocarditis, so it is recommended to be used with caution and at low dosages
Define mild moderate and severe pulmonary hypertension
mild ( < 50 mmHg), moderate (51–75 mmHg), or severe ( > 75 mmHg)
Describe how NO is produced and what is the mechanism for it’s vasodilatory effect
NO is produced from L-arginine and oxygen by the enzyme nitric oxide synthase (NOS). Nitric oxide travels to smooth muscle, where it stimulates the enzyme guanylate cyclase (GC) to convert guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). cGMP inhibits calcium release and ultimately leads to pulmonary vasodilation; cGMP is inactivated by phosphodiesterases
Describe how PGI2 is produced and what is the mechanism for it’s vasodilatory effect
Prostaglandin I2 (prostacyclin or PGI2) is an eicosanoid produced by vascular endothelial cells via prostacyclin synthase. PGI2 stimulates adenylate cyclase (AC) and enhances the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). cAMP decreases intracellular calcium stores, leading to pulmonary vasodilation
Define hypoxic vasoconstriction
Alveolar hypoxia is associated with pulmonary vaso-constriction. This response targets perfusion to better ventilated lung regions, improving ventilation:perfusion matching
What is the Evian Scheme defined in human medicine for Pulmonary Hypertension?
Class I pulmonary arterial hypertension (PAH)
Class 2 PH due to left-sided heart disease
Class 3 PH due to pulmonary disease
Class 4 PH due to thromboembolic disease
Class 5 PH due to unclear or multifactorial mechanisms
Mention 2 causes of Class I PH (PAH) in VM
HW disease, congenital shunts (PDA, atrial/ventricular septal defects)
What is the Eisenmenger’s syndrome?
A large or chronic left-to-right shunt allows significant blood flow to the right side of the heart, leading to severe pulmonary vascular changes.
These changes promote increased right- sided cardiac pressures, and eventually the right-sided cardiac pressures exceed left-sided pressures; due to the pressure differences, shunt reversal occurs, and blood flows through the shunt from the right side of the heart to the left.
As a result of right-to-left shunting through the defect, deoxygenated blood enters the systemic circulation and leads to cyanosis and polycythemia.
What is the Kussmaul’s sign
Increased jugular distension during inspiration
How do you diagnose Eisenmenger’s syndrome?
Bubble study??
Right ventricular pressure is assumed to be same as _____? In the absence of pulmonary stenosis.
Pulmonary Artery Pressure (PAP)
In which views is tricuspid regurgitation measured?
Right parasternal short axis basilar view and left parasternal apical view
How is PAP calculated from the Tricuspid Regurgitation velocity
Using the modified Bernoulli equation (pressure gradient (mmHG) = maximum TR velocity (m/s)2 × 4), the TR velocity is converted to pressure and is considered an adequate indirect measurement of PAP
Which diagnostic test is the gold standard for diagnosis of PH
Right heart catheterization and direct measurement of PAP
Which advanced echocardiographic techniques can be employed in the absence of TR to diagnose PH?
Pulmonary artery profile
Measurement of pulmonary artery acceleration time and ejection time
Tricuspid annular plane systolic excursion (TAPSE)
Assessment of right ventricular myocardial function via the TEI Index
Tissue Doppler imaging
What are common echocardiographic findings in a patient with PH that show clinical signs?
Moderate to seere right sided cardiac changes: RA enlargement, RV dilation and/or hypertrophy, septal flattening, pulmonary artery dilation.
Justify why antiplatelet drugs should be used in a patient with PH
o Antiplatelet therapy should be instituted in cases of PH due to thromboembolic disease
o Given that PH is associated with cellular changes that promote platelet-induced vascular changes, such as serotonin-associated vascular remodeling, there is some rationale for use of platelet inhibitors in other classes of PH
Explain the mechanism of action of PDE-5 inhibitors
Phosphodiesterase 5 (PDE-5) is highly concentrated in pulmonary vessels, leads to the breakdown of cGMP. Inhibition of PDE-5 at higher concentrations of cGMP, decreased Ca release, and therefore improved vasodilation
How could a prostacyclin analog help in the treatment of a patient with PH?
Prostaglandin I2 (prostacyclin or PGI2) is an eicosanoid produced by vascular endothelial cells via prostacyclin synthase. PGI2 stimulates adenylate cyclase (AC) and enhances the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). cAMP decreases intracellular calcium stores, leading to pulmonary vasodilation.
What is the Virchow’s triad?
blood stasis, hypercoagulability, and endothelial damage. It is generally believed that two factors have to be present for thrombosis, but one also influences the others.
What is the difference between an arterial and a venous thrombus?
o Venous thrombus à at low shear stress rates (0–1000 s−1), fibrin generation (i.e. secondary hemostasis) plays a major role. Therefore, a venous thrombus is primarily composed of red blood cells embedded within a fibrin meshwork
o Arterial thrombosis –> where high shear stress conditions (>10 000 s−1) predominate, and platelet adhesion to the endothelium is the most important part of thrombus formation. Therefore, an arterial thrombus is primarily composed of platelets
What parameters could indicate presence of active fibrinolysis/ active clot formation?
Low platelet count, fibrin degradation products, D dimers / Hypercoagulable TEG VCM
Mention 3 thrombolytic drugs
Tissue plasminogen Activator, urokinase, streptokinase
What is the mechanism of action of Aspirin
Acts on the arachidonic acid pathway and irreversibly inhibits the COX pathways. These enzymes (COX 1 and COX 2) catalyze the conversion of arachidonic acid to PGH2, the pre- cursor for several metabolites including thromboxane A2 (TXA2). TXA2 enhances platelet function and promotes platelet aggregation and vasoconstriction / Also produces a permanent defect in platelet TXA2 synthesis during the entire life of the platelet (7–10 days).
What is the Aspirin half life in cats?
38h
What is the mechanism of action of Clopidogrel
Thienopyridine that selectively inhibits ADP-induced platelet aggregation but has no direct effects on arachidonic acid metabolism. It requires hepatic biotransformation to produce the active metabolite.
What is the mechanism of action of heparin
It complexed with antithrombin to form heparin:antithrombin complex –> catalyzes the activity of it. Inhibits coagulation factors II, IX, X, XI, XII
Which factors are the most sensitive to the heparin:antithrombin complex?
II and X
What is the molecular weight of UFH and LMWH
UF: mean of 15.000 / LMWG 4000 to 5000
Why are the biological and pharmacokinetics of UF so variable?
They depend on the proportion of heparin molecules large enough to bind thrombin
How would you monitor a patient on UFH therapy?
aPTT therapeutic target range 1.5 to 2.5 times normal control value
Why does LMWH has reduced anti-IIa activity relative to anti-Xa?
only 25–50% of the heparin molecules in LMWH are large enough to inhibit factor IIa, although all retain the capacity to inactivate factor Xa.
Why does aPTT tends to be prolonged in a patient with UF treatment?
it’s a reflexion of the inhibition of factor IIa
Which type of heparin has a longer half life and why?
LMWH has a reduced affinity for binding to plasma proteins or cells compared with UFH –> more predictable dose–response relationship and longer half-life
What is the recommended lab method for monitoring LMWH therapy?
Chromogenic assay of anti-factor Xa activity
What is the percentage of cats with FATE that were diagnosed with cardiac disease before having that episode?
10% (90% of cats have underlying cardiomyopathy, but less than 10% are previously diagnosed with cardiac disease)
Mention 4 diagnostic tests for FATE
Glucose and lactate peripheral compared with affected limb, Lack of doppler flow, direct visualizetion of the thrombus on US, angiography
According to the FATCAT study, how would you choose tha antithrombotic therapy in a cat with ATE
FATCAT study -> Clopidogrel administration was associated with significantly reduced likelihood of recurrent FATE compared to aspirin and had a longer median time to recurrence. Recurrence rates of 75% and 49% with aspirin and clopidogrel respectively.
Mention poor prognostic indicator in FATE
of limbs affected (1 limb = 70% survival to discharge / 2 limbs = 25% survival to discharge)
Motor function
CHF
Hypothermia
Bradycardia
Phosphorus levels
Mention 6 disease processes that have been implicated in distal canine aortic thrombosis?
o PLN / PLE - Endocrinopathies: hyperadrenocorticism, diabetes mellitus, hypothyroidism - liver disease - neoplasia - infective endocarditis - Immune-mediated diseases where chronic or higher doses of steroids are required à IMHA, ITP or Addison’s disease.
What is cardiorenal syndrome?
Risk of Cardiorenal syndrome based on fluid status
Why is it important to monitor CO?
Gold standard for measuring CO?
Flowmeter - surgically applied surrounding a vessel and measures the SV - only used in research
Second best to monitor CO?
o PV loop diagram
o Catheter inside the LV with ultrasound waves attached to the catheter and will give several volumes that will be added and give us PV loops.
o Why is it not used clinically? If there is a tiny bubble of air, goes straight into the brain, will not pass through lungs to be caught. Much more dangerous.
Indicator dilution method
o Clinical gold standard.
o CO = vol indicator (temp patient - temp indicator) / f time
Methods for CO monitoring
o They all measure things that go in and out of the heart, an indicator. Depending on which indicator it has different names.
o Swan Ganz - with temperature
o LiDCO - lithium
o CO status - ultrasound dilution
o PiCCO
o The AUC is inversely proportional to CO
Swan Ganz
o From Ra -> RV -> PA
o Measures temperature changes - we inject a big bolus of 0.9%NaCl
o There is a thermometer at the tip of the catheter that will measure temperature drops.
o Temperature in graph is negative cause it is less than initial temperature
o Curve will tell us CO
Swan Ganz - graph, which one has lower or higher CO?
Swan Ganz catheter parts
PAP diagram
What information will the PAP give us? And the PCWP?
o PAP - resistance for lungs
o PCWP - pulmonary circulation, resistance and how volume status is.
Swan Ganz information
Risks / disadvantages of Swan Ganz
o Size of the patient - only made for humans and babies, not possible to use it in large animals
o We need a cut down to introduce it
o Myocardium damage
o Pulmonary rupture - if balloon ruptures
o Contraindications - LBBB - risk of complete block. Hypocoagulation.
PiCCO
o Instead of finishing in the PA, finish in the RV or even vena cava
o Transpulmonary thermodilution - PiCCO plus
o PiCCO stands for Pulse Contour Cardiac Output. The “i” in PiCCO was added to create a pronounceable word.
o The PiCCO Technology is based on transpulmonary thermodilution and arterial pulse contour analysis. The thermodilution measurement needs to be performed correctly and the arterial pressure curve needs to be of a certain quality.
o Limitations - requires femoral artery catheterization, indicator loss over time, charge per catheter
Comparison of direct Fick method vs thermodilution 1 - theoretical bases and equipment
Comparison of direct Fick method vs thermodilution 2 - advantages and limitations
LiDCO
o Lithium dilution cardiac output is a minimally invasive indicator dilution technique for the measurement of cardiac output.
o Any arterial line works, does not need to be the femoral (like with PiCCO)
o Lithium injected via central line. From an artery, sample is collected and machine detects amount of lithium.
o Limitations: bleeding out (operator, depending on how much sampling, blood loss over time), indicator stable over time (will not leave the body easy over time), clots, cytokines inflammation.
CO status
o Saline velocity dilution method (aka ultrasound velocity dilution method)
o Ultrasound dilution method. Injects saline in the system and causes hemodilution. The viscosity of the blood changes for that period of time. That is the indicator, the viscosity change, not the saline itself.
o In this case arterial catheter is connected to a central line, there is no blood loss like in LiDCO methods.
o Less invasive than PAC, blood returned to the patient, no indicator accumulation.
o Reasonable bias and limits of agreement.
o Limitations - placement of arterial line. Patient should be sedated. Not bad for small patients.
Why do we normally do not use dilution methods clinically?
They are very expensive
Pulse contour method
o Arterial line -> arterial pulse wave. The stronger the heart pumps, the stronger the arteries pump.
o Had good correlation in humans the AUC from the arterial line. For every AUC it gives you a SV.
o It correlates well in stable patients where CO is constant, when it changes there is not good correlation
Arterial waveform variation
o Pulse pressure variation = (PPmax - PPmin / PPmean) x 100
o PPmean = (PPmax + PPmin) / 2
o To predict fluid responsiveness in MV patients
o MV - BP increases on inspiration, decreases on expiration (opposite of spontaneous breathing)
o Normally PPV <5mmHg
Fick method
o Requires a PAC
o Helps to measure the oxygen consumption based on SvO2
Fick principle
Fick method equations
Fick principle w/CO2 (NICO)
Fick (NICO) equation
Capnography
