Cardiovascular Flashcards
Write down the equation of systemic vascular resistance (SVR).
SVR = (MAP - CVP)/CO x 80
80 converts the unit from wood unit (mmhg/L/min) to metric (dynes/sec/cm-5)
Write down the equation of pulmonary vascular resistance (PVR).
PVR = (MPAP - PAWP)/CO x 80
80 converts the unit from wood unit (mmhg/L/min) to metric (dynes/sec/cm-5)
What is the terminal arterioles called?
Metarterioles
What are the two theories about acute local blood flow control in respond to metabolic need?
1) Vasodilator substance theory
When there is increased tissue metabolism or presence of oxygen deficiency, the tissue will release vasodilator substances (e.g. adenosine***, CO2, hydrogen ion, potassium ion, histamine). This substance will diffuse locally and cause local vasodilation
2) Oxygen demand theory
Smooth muscles need oxygen to contract. When there is increased metabolism and oxygen deficiency, vascular smooth muscle cannot constrict which lead to local vasodilation
*Reactive hyperemia vs Active hyperemia
Within a range of arterial blood pressure, the body is able to maintain local blood flow within a certain range. This is called Autoregulation. What are the two theories about autoregulation?
1) Metabolic theory
- Oxygen and nutrient deficiency → increase vasodilator substances → increase blood flow
- Too much oxygen & nutrient & blood flow → wash out vasodilator substances → vasoconstriction
2) Myogenic theory
- Stretch-induced vascular depolarization → Increase intracellular calcium…etc → vasoconstriction
- Metabolic factors appear to override the myogenic mechanism in circumstances in which the metabolic demands of the tissues are significantly increased
What is NO synthesized from?
L-Arginine
O2 + L-Arginine → NO + L-Citrulline (via NOS)
What is the half-life of NO?
6 seconds
Explain how NO causes vasodilation (2 mechanisms)
1) NO activates guanylate cyclase → converts cGTP to cGMP (important second messenger) → cGMP activates cGMP-dependent protein kinase → vasodilation
2) activates and opens KsubCa channels (via nitrosylation) –> outward flow of K –> hyperpolarization
What stimulates eNOS?
1) Shear stress
2) Vasoactive substances (e.g. acetylcholine, bradykinin, adenosine, substance-P)
3) Angiotensin II (usually it is a vasoconstrictor but this is a mechanism to protect for excessive vasoconstriction)
True or False: Angiotensin II, a potent vasoconstrictor, can stimulate NO production.
True
What is iNOS?
It is inducible nitric oxide synthase. It does not express in resting cells and needs to be induced by cytokines or microbial products.
Does increased potassium level cause vasoconstriction or vasodilation?
Vasodilation
How does methylene blue cause vasoconstriction?
It inhibits the NO/cGMP pathway
Does increased magnesium level cause vasoconstriction or vasodilation?
Vasodilaiton
Does increased calcium level cause vasoconstriction or vasodilation?
Vasoconstriction
Does increase plasma hydrogen ion concentration cause vasoconstriction or vasodilation?
Mild arterial vasodilation
Does increase plasma CO2 concentration cause vasoconstriction or vasodilation?
Moderate vasodilation peripherally, marked vasodilation in the brain
In pulmonary circulation is the opposite where increased CO2 causes vasoconstriction
Define mean systemic filling pressure.
The pressure in the systemic circulation when there is no flow. It is composed of unstressed volume and stress volume.
What is the formula for venous return?
Venous return = [(Mean systemic filling pressure - right atrial pressure)/Venous resistance]
Describe Frank-Starling curve.
Within certain range, the increased left ventricular end diastolic volume will increase the stroke volume due to the stretch of the myocytes leading to more forceful contraction.
* The foundation concept of fluid responsiveness*
- x axis: left ventricular end diastolic volume (preload)
- y axis: stroke volume (or cardiac output)
What is the formula for shock index?
Shock index = HR/SBP
What is the shock index to differentiate shock and normal dog?
SI ≥ 0.9 → shock
Which electrolyte abnormality is associated with U wave?
Hypokalemia
True or False: Hypokalemia leaves the myocardium refractory to the effects of class I antiarrhythmic agents (e.g. lidocaine)
True
In hypokalemia, the hyperpolarized state of cardiac cells means that a larger fraction of sodium channels remains in a resting state rather than an inactivated state. Class I antiarrhythmic drugs are more effective at blocking sodium channels that are in the inactivated state. Therefore, with fewer sodium channels in the inactivated state during hypokalemia, these drugs are less effective.
Lidocaine is more effective with low pH and hyperkalemia
True: ideal anti-arrhythmic for damaged myocardial tissue
What is normal arterial oxygen content?
20 ml/dL
What is normal cardiac output in dogs and cats?
Dog: 125-200 ml/kg/min
Cat: 120 ml/kg/min
What is normal oxygen extraction ratio?
20-30%
What is normal DO2 and VO2?
DO2: 20-35 ml/kg/min
VO2: 4-11 ml/kg/min
What is the definition of hypotension?
SAP < 90 mmHg or MAP < 60 mmHg
What are the 4 organ systems affected by hypertension?
Renal
Eyes
Cardiovascular
CNS
When you are able to palpate the femoral pulses, what is the estimated SAP?
> 60 mmHg
What is the estimated SAP when you can palpate the dorsal pedal pulses?
> 90 mmHg
What blood pressure is Doppler measured? SAP, MAP or DAP?
SAP
During Doppler blood pressure measurement, if the limb with the cuff is below the RA, does that cause falsely lower or higher BP?
Falsely higher
When the limb is below the level of the heart (and specifically the right atrium), gravity causes an increase in hydrostatic pressure in the blood vessels of the lower limb. This increased pressure adds to the actual blood pressure and is detected by the cuff, leading to a higher reading than the true systemic blood pressure.
- Limb below RA: Causes a falsely higher BP reading.
- Limb above RA: Would cause a falsely lower BP reading.
What is the most reliable reading from standard oscillometry BP measuring?
MAP
What is the difference between High-definition oscillometry and standard oscillometry?
1) HDO can measure more accurately in a wider range
2) HDO can obtain a more accurate reading in the presence of arrhythmias
3) HDO can obtain SAP, MAP and DAP
HDO devices perform realtime analysis of arterial wall oscillations to obtain pressure wave amplitudes →
Fill in the pressure within each camber & vessel.
Describe how to set up a continuous arterial blood pressure monitoring system
1) Place an arterial line
2) Prepare a bag of 1L saline with heparin (1-2U/ml), a transducer, a monitor and non-compliant arterial line monitoring extension tube. Attach them together.
3) Fill the entire arterial monitoring system with heparinized saline.
4) Attach the arterial BP monitoring system to the arterial catheter and the monitor.
5) There should be a 3-way stopcock on the arterial BP monitoring system. Turn it to close the patient end and open the monitor end to the atmosphere. Keep the system at the level of RA and zero the system.
6) After the system is zero. Turn the 2-way stopcock to close the opening to the atmosphere and connect the monitor to the patient. You should be able to obtain the arterial waveform.
7) Perform a fast flush test to determine if it is necessary to adjust the system and optimize its dynamic’s response
What are the 3 important steps for arterial BP transducer setup?
1) Zeroing
2) Calibration
3) Leveling
Is CVP close to right ventricular systolic pressure or right ventricular diastolic pressure?
RV diastolic pressure (= filling pressure of right side of the heart)
What is normal CVP?
0 - 5 cmH2O
What are the 3 main factors that can affect CVP?
1) Venous return
- Circulating blood volume
- Venous wall compliance
2) Right-sided cardiac diseases
3) Intrathoracic/intraperitoneal pressure
When the CVP is low, what are the two main differential?
Vasodilation (venodilation)
Decreased systemic circulating blood volume
When the CVP is normal, beside normovolemia, what are the two other possibilities?
Compensated hypovolemia
Compensated hypervolemia
List 10 differentials for elevated CVP
1) Hypervolemia
2) Systemic hypertension or marked vasoconstriction
3) Occlusion of the catheter
4) Right sided cardiac disease (e.g. tricuspid regurgitation, right sided systolic dysfunction)
5) Pulmonary hypertension
6) Pericardial effusion
7) Pneumothorax
8) Marked ascitis
9) Pleural effusion
10) Mechanical ventilation (PEEP)
11) Intrathoracic mass
When we place an intravscular catheter for pressure measuring, ideally the catheter should not occupy more than ___% of the lumen. What is that number?
10
How many cmH2O equals 1 mmHg?
1.36 cmH2O = 1 mmHg
When the animal is in sternal recumbency, how do you estimate the height of RA during the leveling or CVP transducer?
Draw a vertical line from sternum to the top of spinous process caudal to the scapula. The RA is at about 40% of the height of the line.
Describe how is the arterial waveform generated?
When the pressure waves go through the vessels, the reflection will create multiple oscillating waves with different frequency and amplutide (Fourior series). The arterial waveform is the summation of those oscillating waves
This is arterial blood pressure waveforms. Name 1-6.
1: Systolic upstroke
2: Systolic peak pressure
3: Systolic decline
4: Dicrotic notch (incisura)
5: Diastolic runoff
6: End-diastolic pressure
Explain how Dicrotic notch is created.
The elastic recoil of the arteries with the closed aortic valves cause a slight and transient increase of the arterial blood pressure.
In an arterial BP waveform, which part indicate MAP?
The shaded area beneath the arterial pressure curve
List 5 factors that can affect the patient’s direct arterial BP monitoring reading.
1) System’s dynamic response
2) Presence of air bubbles in the tubing
3) Respiration
4) Arrhythmias
5) Catheter location/placement
What are the two major components when it comes to a ABP monitoring system’s dynamic response.
1) Natural frequency
2) Damping coefficient
- They are determined by the system’s physical properties, specifically mass, elasticity, and friction
What happen when the natural frequency of the ABP monitoring system coincides with the natural ABP’s frequency?
The reading and the waveform will be exaggerated due to summation of the waveforms (“summation effect”) → higher SAP and lower DAP → overshooting, ringing
When the natural frequency of an ABP monitoring system is not adequate, it’s usually too low or too high?
Too low
- Ideally need to > 12 Hz or as high as possible
What does damping mean in the ABP monitoring?
Loss of the pulse pressure energy when the waves travel from the catheter to the transducer.
List 4 causes of damping in ABP monitoring.
1) Friction resistance along the line
2) Absorption of energy by the tubing and system
3) Air bubbles
4) Line occlusion
Does the higher damping coefficient mean more likely to overdamp or underdamp?
Higher damping coefficient → more significant of the damping → overdamp
What can we see in overdamped and underdamped arterial waveforms?
Overdamped: loss of details (e.g. dicrotic notch), slurred waveform
Underdamped: falsely high SAP and falsely low DAP, extra spikes and details that are non-physiological
What is the natural frequency of this ABP monitoring system?
25/1.7 = 14.7 Hz
- Note the number of blocks between oscillation peaks
Describe how to determine the damping coefficient with this figure.
17/24 = 0.71 (amplitude ratio)
According to the chart, the damping coefficient is 0.11
- Measure the length of two successive oscillations (i.e., from peak to valley, and from that same valley to the next peak).
How many oscillations after the fast flush in the fast flush test will be considered underdamping?
> 2 oscillations
- Normally should be 2 oscillations
Does air bubbles cause underdamp or overdamp?
- Very small air bubble may cause underdamp (act as a spring as they compress and decompress easily. This allows the pressure waveform to oscillate excessively, leading to an amplified or exaggerated response)
- Large bubble will cause overdamp (acts like a cushion, absorbing and dissipating the energy of the wave rather than transmitting it accurately to the transducer)
As the arterial waveforms move from central to peripheral, does the systolic peak gets higher or lower? What about the end-diastolic pressure?
Initial upstroke becomes steeper
Systolic peak gets higher
End-diastolic pressure gets lower
- The waveform is delayed; the dicrotic notch appears later and appears more slurred
- distal pulse amplification
During mechanical ventilation, does the pulse pressure decrease or increase during inspiration?
Increase
- The opposite during spontaneous ventilation
What are the three hallmarks for arterial waveforms in aortic stenosis?
1) Systolic upstroke becomes less steep
2) Loss of dicrotic notch
3) The systolic peak pressure may decrease in severe case
What are the three hallmarks for arterial waveforms in aortic regurgitation?
1) Very steep systolic upstrokes
2) Increased pulse pressure
3) Decreased end-diastolic pressure
Explain what Corrigan pulse is and list four conditions that we may observe it clinically.
Corrigan’s pulses is the rapid elevated and collapse pulse (increased pulse pressure but very short duration for each pules).
Aortic regurgitation, PDA, severe anemia, hypertension
When the ABP monitoring shows hypotension, list 5 steps you would do to check it.
1) Examine the patient to see if the patient’s clinical signs fit hypotension
2) Check the ABP tubing to see if there is any kink, blood clot or air bubbles
3) Check the pressured fluid bag to make sure the pressure is higher than 250 mmHg
4) Check if the arterial catheter is patent
5) Check if the patient’s position has change and if re-zeroing is needed.
Describe how to set up a CVP monitoring system (with water manometer).
1) Flush the patient’s central venous catheter with heparinized saline to make sure it’s patent
2) Keep the water manometer vertical (can use an IV pole). Collect the three way stopcock with manometer, fluid set and tubing toward the CVC (do not connect yet)
3) Close the manometer end. Fill the entire non-compliant tubing with normal saline. Connect the tubing to CVC.
4) Close the patient end. Fill the water manometer with 10-20 cm of normal saline
5) Keep the zero marker of the water manometer at the level of right atrium.
5) Close the fluid set end. Allow the water manometer and patient’s end to equilibrate.
how many percentage of systemic blood volume is in the venous system?
65%
What is the formula for transmural pressure?
Transmural pressure = intravascular pressure - extravascular pressure
When using CVP to assess volume responsiveness, what is expected to see in euvolemic patient (i.e. how many cmH2O CVP will increase? how long does it take to return to baseline?)?
CVP usually will increase 2-5 cmH2O and will return to baseline after 15 min
- Hypovolemic patient → CVP rises minimally or rapidly returns to baseline
- CVP takes longer to return to baseline → volume overload, cardiac dysfunction, restrictive pericardial disease
Name which cardiac cycle/phase are those waves and descents represent and what happen to the heart during that cycle/phase.
a wave: end-diastolic; right atrial contraction
c wave: early-systolic; isovolumetric ventricular contraction; tricuspid valves are pushed toward RA
x descent: mid-systolic; right atrial relaxation
v wave: end-systolic; systolic filling of RA (venous return)
y descent: early-diastolic; early ventricular filling
What is the formula to estimate CVP from the waveform?
CVP = (a wave peak + x descent base)/2
What change of CVP waveform can we see in patient with VPCs?
Cannon “a” wave
What change of CVP waveform can we see in patient with atrial fibrillation?
Absence of a wave and prominent c wave (due to overfilling of RA)
What change of CVP waveform can we see in patient with tricuspid regurgitation?
Broad, tall systolic c-v wave, beginning in early systole and obliterating the systolic x descent in atrial pressure.
Name the function of the Swan-Ganz catheter ports from top to bottom.
- Thermistor port
- Measure CVP (blue; proximal)
- Measure pulmonary artery pressure, collect sample for SvO2 (yellow)
- Drug administration port
- Balloon inflation port; measure PAWP (red)
Define preload and afterload.
Preload: a measure of the ventricular myocardium stretch at the end of diastole
Afterload: the force/resistance which the ventricles need to overcome to eject the blood
What is the formula for cardiac index?
Cardiac index (L/min/m2) = cardiac output/body surface area in m2
What is Fick’s principle and what is the formula modified from this principle to measure cardiac output?
Total uptake of the oxygen by the peripheral tissues equal the product of total blood flow through the tissues and the arteriovenous oxygen concentration difference.
- it can also be used for CO2 production
What is the formula when using CO2 rebreathing method to measure cardiac output
Although Fick’s method is the gold standard for CO monitoring, what are the major disadvantages?
- the patient is anesthetized and intubated to measure the VO2
- patient needs to be cardiovascularly stable
- not a real-time measurement as blood gas analysis is required
- requires a central line to have a mixed venous sample (PA)
Using the Fick’s method with CO2 production vs O2 consumption to determine CO
Patient is anaesthetised, intubated and hooked to a proprietary rebreathing circuit containing CO2. If CO2 significantly increases CO is high as more blood reaches peripheral tissues and carries more CO2 vs low CO2 exhaled = low CO and low tissue perfusion
When using thermodilution to measure cardiac output, where is the indicator (saline) injected and where is the dilution measured?
There are two methods:
- transpulmonary: injection via jugular vein and sampling on peripheral vessels (i.e. femoral artery)
- pulmonary artery Injection: injection and sensor within the PA
What is transesophageal echocardiography measured to evaluate the cardiac output?
Cross-section area of left ventricular outflow tract & aortic blood velocity
What is mean pulmonary artery pressure in dogs?
10-20mmHg
What is normal cardiac index in dogs?
3.5 - 5.5 L/min/m2
What is normal stroke volume in dogs?
1.5-2 ml/kg/beat
What is normal SVR and Pulmonary vascular resistance?
SVR: 0.5-0.8 mmHg/kg/min
PVR: 0.04-0.06 mmHg/kg/min
10x difference!
What is normal pulmonary arterial wedge pressure in dogs?
5-12 mmHg
List 7 potential errors that can cause inaccurate CO measurement when using thermodilution method.
- Arrhythmias
- Respiration (ideally measure at end-expiration)
- Intracardiac shunt
- Thermistor probe problems (malfunction, got blood clote)
- Severe hypotension
- Inadequate indicator injection
- Concurrent large volume fluid/med administration
For the CO measurement using CO2 rebreathing method, what is the name of the monitor? What is the formula used in this monitor to calculate CO?
NICO
- The equation is for partial rebreathing technique
This is the graphs for thermodilution result. Which one indicates low cardiac output, and which one indicates high cardiac output?
b) indicates high cardiac output
c) indicates low cardiac output
List 4 possible complications for thermodilution method.
1) valve damage, endocarditis
2) rupture of RA or PA
3) blood clot formation, air embolism
4) arrhythmias
What technique does PICCO use to measure CO?
Transpulmonary thermodilution
- Inject a cold fluid bolus in jugular vein and measure its changes in femoral artery
- It can also analyze the pulse waveform contour and therefore obtain more information (e.g. preload, afterload…etc)
How does LiDCO measure CO?
Inject a fixed dose of lithium chloride and then has a lithium-selective electrode placed at the peripheral arterial catheter
- It can also analyze the arterial pulse waveform
What are the two CO monitor system that integrate arterial waveform?
PiCCO
LiDCO
True or False: When using Fick’s principle to measure CO, the result won’t be accurate if there is a shunt.
True
Describe how to place a Swan-Ganz catheter.
1) Attach ECG to the patient
2) Clip and aseptically prepare the jugular vein. Fill the introducer with heparinized saline and Insert the introducing catheter.
3) Get the thermodilution catheter and attach **distal port to pressure transducer **via a three-way stopcock and flush the system with heparinized saline.
4) Attach continuous flush line to the transducer and pressurize the bag to ≥200 mm Hg.
5) Zero the pressure transducer.
6) Insert the thermodilution catheter through the introducer catheter to about 20 cm and verify that the pressure tracing reflects a central venous pressure waveform.
7) Advance the catheter with the natural curve of the catheter aimed toward the sternum of the animal; watch for a typical ventricular waveform.
8) If the catheter advances to the **50-cm mark **without entering the right ventricle, withdraw it to the 20-cm mark and start again.
9) If the pressure tracing becomes damped, flush the distal port with the transducer’s fast flush device; if the pressure tracing abruptly ceases followed by a rapid, linear increase, the end-hole has butted up against a vessel or heart chamber wall and should be withdrawn slightly and then reinserted.
10) Once the catheter tip has entered the right ventricle, inflate the balloon with 1 mL of air and advance it further until the pressure waveform indicates that the catheter tip has entered the pulmonary artery.
11) With the balloon inflated, advance the catheter until the pressure tracing reflects occlusion of a branch of the pulmonary artery; deflate the balloon and verify a good pulmonary artery tracing.
12) Bandage the catheter and introducer set aseptically and occlusively.
What is normal arterial and venous oxygen content in dogs?
Arterial: 17.8 ml/dL
Venous: 14.2 ml/dL
As the Swan-Ganz catheter enters the heart and advances slowly, what are the pressure waveform change do you expect to see? Order them from the beginning to the end.
C → D → A → B
Comparing the PAWP and CVP, the c wave is more difficult to discern in PAWP. List 2 reasons to explain why.
- Damping when the waveform travels from LA to pulmonary artery
- ## There is shorter time between LA contraction and LV contraction compared to RA & RV contraction → a & c waves may superimposed
List 4 ECG abnormalities that can be seen in hypokalemic patient.
1) Atrial/ventricular tachyarrhythmias
2) Prolonged QT interval
3) Decreased T wave amplitude
4) ST segment elevation/depression
What is the ECG abnormalities that can be seen in hypocalcemia?
Prolong QT interval
- If hypercalcemia → shortening of QT interval
When patient experiences hypertension crisis, how fast shouldn’t the BP drop?
No more than 25% in 1 hour
What is the formula for Reynold’s number? What is it used for?
It is used to evaluate the tendency of turbulence to occur
What is the cutoff of Reynold’s number for the turbulence at the branch of vessels?
200-400
What is the cutoff of Reynold’s number for definitive turbulence no matter branch or smooth vessel?
> 2000
What is the formula for Poiseuille’s law?
In the systemic circulation, where do most of the systemic resistance occur?
Small arterioles (2/3 of total resistance)
Between what blood pressure range can the blood vessels maintain relatively constant flow rate via autoregulation?
75 - 175 mmHg
True or False: Pulse pressure = Stroke volume/arterial compliance.
True
Name 3 blood reservoirs.
1) Spleen
2) Liver
3) Large intra-abdominal veins
4) Venous plexus under the skin
True or False: Lymph from the entire body all flows into the thoracic duct, which empties the lymph into the venous system at the junction of left internal jugular vein and left subclavian vein.
False.
The lymph from right side of the neck and head, right arm, and parts of the right thorax flows into the right lymph duct → right subclavian vein and internal jugular vein
Where does vasomotor center locate?
Medulla and lower 1/3 of the pons
True or False: Under normal condition, there is continuous partial constriction of blood vessels caused by sympathetic nerve. This is called vasomotor tone.
True
True or False: The vasomotor center can not only control vascular tone but also the heart rate.
True
From Guyton: “The lateral portions of the vasomotor center tran mit excitatory impulses through the sympathetic nerve fibers to the heart when there is a need to increase heart rate and contractility. Conversely, when there is a need to decrease heart pumping, the medial portion of the vasomotor center sends signals to the adjacent dorsal motor nuclei of the vagus nerves, which then transmit parasympathetic impulses through the vagus nerves to the heart to decrease heart rate and heart contractility.”
True or False: The baroreceptors response is linear to the blood pressure.
False
When BP below 50-60 mmHg, baroreceptors at the carotid sinus do not respond.
When BP below 80 mmHg, baroreceptors at the aortic arch do not respond.
Explain how the circulatory reflex work after it is initiated by the activated baroreceptors.
The baroreceptor signal enters the vasomotor center → the secondary signal inhibits the vasoconstrictor center and stimulates the vagal parasympathetic center → vasodilation, decrease heart rate and contractility
List 3 conditions that will activate the chemoreceptors.
1) Low oxygen
2) High CO2
3) Increased H+ ion
Where do chemoreceptors locate?
2 carotid bodies locate at the carotid bifurcation; 1-3 aortic bodies locates adjacent to the aorta
List 3 mechanisms of how the low pressure baroreceptors (especially atrial receptors) regulate high blood volume.
Low-pressure receptors are stretch receptors in pulmonry artery, atria and vena cava. They respond to changes in blood volume.
1) decrease in SNS tone –> afferent renal vasodilation → increase GFR and fluid filtrated through the glomerulus
2) Decrease ADH release → decrease water reabsorption
3) Release atrial natriuretic peptide → decrease sodium and water reabsorption at the nephrons
4) Bainbridge reflex –> increased atrial stretch –> increase HR to avoid pooling of blood
Describe Bainbridege reflex.
Increased atrial pressure leads to increased heart rate and contractility.
- The afferent limb of the reflex within this signal, when activated takes sensory information from the vagus nerve to medulla oblongata, and the efferent limb sends out inhibitory signals by reducing vagus nerve tone and increasing the sympathetic outflow.
What is the reflex associated with the respiratory sinus arrhythmia?
Bainbridge reflex vs vagal reflex?
Inspiration → increased HR
Expiration → decreased HR
What happen to heart rate and BP during CNS ischemic response?
Increased sympathetic tone → HR and BP elevate
How will the cardiac output curve and venous return curve change during sympathetic stimulation?
When does the S1 heart sound happen?
When the mitral and tricuspid valves close
Isovolumetric contraction
When does the S2 heart sound happen?
When the aortic and pulmonic valves close
Isovolumetric relaxation
Explain the splitting S2.
S2 heart sound is composed of closing of aortic valve and closing of pulmonic valve. Aortic valve usually close very slightly before pulmonic valve.
During inspiration, the intrathoracic pressure decreased → increased venous return → more blood in the RV → pulmonic valve open for a bit longer because more RV volume → less blood return to LA → slightly decreased LV volume → aortic valve closes earlier due to shortening emptying time
What is S3 heart sound and when does it usually happen?
- It is also called ventricular gallop
- When mitral or tricuspid valves open and the blood is passively filling the ventricular → S3 is the sound when the large volume of blood strikes a very compliant ventricle
- Early diastole
- Often heard in dogs with DVM
What is S4 heart sound and when does it usually happen?
- It is also called atrial gallop
- When atria contracts to force the blood into a very non-compliant ventricle
- End diastole
- Often heard in cats with HCM
What is the resting membrane potential for ventricular myocardium? What about SA nodal cells?
Ventricular myocardium: -85 mV
SA nodal cells: -55 ~ -60 mV
Which one is RBBB and which is LBBB?
A: LBBB
B: RBBB
List 3 differences between myocardium and skeletal muscles.
1) action potential of myocardium is caused by fast sodium channels and L-type calcium channels; AP of skeletal muscles is caused by fast sodium channels only
2) The source of Ca in myocardium is from extracellular space; while in skeletal muscles it’s from endoplasmic reticulum
3) There is no plateau phase in skeletal muscle AP
Skeletal and myocardial muscle are _____ filament regulated while smooth muscle is ____ filament regulated
skeletal and myocardial muscles are THIN filament regulated (Calcium binding to troponin key step for shifting of tropomyosin interaction between actin and myosin) vs smooth muscle requires Ca binding to calmodulin to activate MLCK which will phosphorilate myosin head and allow detachment from actin
Name each phase and describe how electrolytes move in each phase.
0: depolarization; fast Na channel open and close Kir channels
1: initial repolarization; fast Na channel close, transient outward K channel open (Kv channels ITO current), also Na/Ca exchanger open (Na from phase 0 exists while Ca starts to come in)
2: plateau; L-type Ca channel open, transient outward K channel close
3: rapid repolarization; L-type Ca channel close; slow and rapid dealyed K rectifier channel open
4: resting membrane potential; slow and fast delayed K rectifier channel closes, inward rectifier K channel open
In phase 0 which other channels are involved apart from fast Na?
Kir (K inward rectifiers) channels close - these are the one responsible to keep stable membrane potential
Desribe the two-gate structure of fast Na channels
“m” gate is voltage dependent
“h” gate is time dependent
The “m” gate opens when depolarization of the myocyte occurs while the ‘h’ gate closes to terminate Na entry a few millisecond after ‘m’ have opened.
‘h’ then remains close until the cell has partially repolarized –> responsible for absolute refractory period (protects the myocardium from tetany).
The ‘m’ gate closes at late phase 3 –> responsible for relative refractory period.
When the ‘m’ is close, but ‘h’ is open a cell receiving a strong enough stimulus can be depolarized again.
what are the three states of fast Na channels?
inactivated: ‘m’ open but ‘h’ close (absolute refractory period, phase 1,2 and early 3)
resting: ‘m’ close but ‘h’ open (late phase 3 and 4)
open: both ‘m’ and ‘h’ open (only 1-2 milliseconds during rapid depolarization, phase 0)
What is the funny current?
Ion current in pacemaker cells.
Inward flow of Na and outward flow of K via HCN channels (hyperpolarization cyclic nucleotide channels).
HCN channels sensitive to cAMP –> action of sympathetic nervous system and beta blockers on HR.
How does the PSN system decrease HR?
Activates KAch channels –> otward flow of K ions –> hyperpolarization of pacemaker cells
This channel is also acted upon by gamma subunit of Gi protein (A1 adenosine receptors and digoxin)
Which Ach receptors can be found in the myocardium? how do they work?
Muscarinic M2 receptors –> Gi coupled –> drop cAMP + activate KAch (gamma subunit) to hyperpolarize cell and pull the resting potential away from threshold
Describe how excitation-contraction coupling happens.
1) Action potential reaches the T tubules system which leads to depolarization
2) The voltage change will be sensed by dihydropyridine (DHP) receptors which link to the ryanodine receptor channels (Ca release channels) on the sarcoplasmic reticulum
3) The Ca release channels open and release many Ca ions and cause contraction
4) Ca ions are re-uptaken by active calcium channels called SERCA (sarcoplasmic reticulum Ca2+-ATPase). Ca ions are bound with calsequestrin in the sarcoplasmic reticulum
What is the main difference between myocardium and skeletal muscle excitation-contraction coupling process?
The Ca storage in the myocardium sarcoplasmic reticulum is not as abundant as skeletal muscles. The Ca ion inflow during the plateau phase of AP triggers the Ca release from the sarcoplasmic reticulum and the Ca from both extracellular fluid and SR cause muscle contraction
- Myocardial contractility is heavily dependent on the extracellular Ca ion concentration
During myocardial excitation-contraction coupling process, what are the two ways to lower Ca concentration in the cells?
1) SERCA2 (sarcoplasmic reticulum Ca2+-ATPase)
2) Na-Ca exchanger on the sacrolemma
Why does ‘rigor mortis’ occur?
Relaxation is an. ATP-dependent mechanism (Na/Ca exchanger and SERCA need ATP)
What is parvalbumin?
It is a negatively charged cytosolic protein that binds to Ca++ and chaperones it into the SR
This is part of the ‘sarcoplasmic calcium buffering system’
Draw the Wigger’s diagram.
How many percentage of blood in the ventricle is contributed by atrial filling?
20%
What is ejection fraction (EF) and what is the formula? What is normal EF in dogs and cats?
Ejection fraction is the fraction of the blood in the ventricular chamber that is ejected during systole in relation to the total blood volume during end-diastole
EF = SV/LVEDV
Normal EF in dogs and cats: 50-70%
What is the difference between LV and RV pressure.
RV is about 1/6 of LV
On the heart, where do the parasympathetic nerves innervate?
atria
How does SA node generate its self-excitation AP?
Slow Na channel is very leaky and can cause continuous slow Na inflow. When the membrane potential reaches -40 mV, L-type Ca channels open, causing depolarization and generation of AP.
Compare the waveforms, different phases and electrolytes movement in each phases between ventricular and SA nodal AP.
What is hepatojugular reflex and what does it indicate?
Hepatojugular reflex means when the pressure is applied on the liver, the jugular vein becomes distended.
Positive hepatojugular reflex means the heart cannot compensate with increased venous return.
According to ACVIM Consensus Statement, systemic hypertension has three categories, what are them?
Situational hypertension
- White coat hypertension
Secondary hypertension (most common)
Idiopathic hypertension
List 5 diseases process that can cause systemic hypertension in dogs and cats.
Cushing disease
Hyperthyroidism
Chronic kidney disease
AKI
Pheochromocytoma
DM
Primary hyperaldosteronism
Which is the most common first manifestation of SH?
The eyes are the most vulnerable organ for TOD.
First manifestation is tortuous retinal vessels followed by multifocal retinal oedema and exudative retinal detachment.
Early aggressive treatment can lead to physical retinal re-attachment but rarely resoration of vision.
Classification of hypertension based on TOD risk
What is the Renal Resistive Index?
Sonographic measure of blood flow resistance in arcuate arteries
RIR = (peak systolic velocity - peak diastolic velocity) / peak systolic velocity
RIR closely correlated with number of organ involved in TOD
RI>0.7 = 3-4 organs involved
What is PRES?
Posterior Reversible Encephalopathy syndrome
Form of acute hypertensive encephalitis - treat with nicardipine (CCB similar to amlodipine but injectable form).
Sudden increase in MAP overcomes autoregulation mechanism
What is the difference between hypertensive emergency and hypertensive urgency?
Hypertensive emergency SAP>180 and evidence of TOD vs hypertensive urgency SAP>180 without evidence of TOD
List 5 medications that can cause systemic hypertension in dogs and cats
Glucocorticoid
Vasopressin
Epinephrine
Phenylephrine
Minerocorticoid
EPO
Phenylpropranolamine
True or False: ACVIM Consensus Statement recommends routine screening of systemic hypertension in dogs and cats.
False
- Patients > 9yrs will be reasonable
According to ACVIM Consensus Statement, SBP above what is considered severe hypertension?
> 180 mmHg
According to ACVIM Consensus Statement, when the initial SBP is < 160mmHg, what is the recommended follow-up plan?
Recheck in 3-6 months
According to ACVIM Consensus Statement, when the initial SBP is between 160-179mmHg without TOD, what is the recommended follow-up plan?
Recheck twice in 8 weeks & recheck for TOD
If the SBP is still persistently above 160mmHg, antihypertensive therapy is recommended.
According to ACVIM Consensus Statement, when the initial SBP is > 180mmHg without TOD, what is the recommended follow-up plan?
Recheck twice in 14 days & recheck for TOD
If the SBP is still persistently above 160mmHg, antihypertensive therapy is recommended.
According to ACVIM Consensus Statement, what are the two main goals for antihypertensive therapy
1) Minimize the risk of TOD (SBP ≤ 140 mmHg; optimal goal)
2) Maintain the SBP ≤ 160 mmHg (minimal goal)
According to ACVIM Consensus Statement, when you start a anti-hypertensive therapy, what is the recommended follow-up plan?
Recheck BP in 7-10 days if no TOD
Recheck BP in 1-3 days if TOD presents
*If BP < 160 mmHg on recheck, the next recheck can be 4-6 months.
Why calcium channel blocker should not be used as a monotherapy in dogs for hypertension management?
Because calcium channel blockers mainly cause renal afferent arteriole dilation → may increase the glomerulus capillary hydrostatic pressure
What is the possible limitation of combining calcium channel blocker and ACE inhibitors or ARB for canine hypertension management?
Calcium channel blockers mainly cause renal afferent arteriole dilation; ACE inhibitors and ARB mainly cause renal efferent arteriole dilation → may not make much change of the glomerulus capillary hydrostatic pressure
What is the first choice of antihypertensive drugs for dogs and cats, respectively?
Dogs: ACE inhibitor
Cat: calcium channel blocker (because of established efficacy)
In cats with systemic hypertension, what is the key predictive factor for survival?
Proteinuria
According to ACVIM Consensus Statement, what is the recommended antihypertensive therapies for cats with hyperthyroidism?
Amlodipine
Beta blocker (atenolol > propanolol as selective Beta 1 blocker and safer for asthmatic cats)
What are the two criteria for systemic hypertension that indicate emergency intervention?
1) SBP > 180 mmHg
2) Signs consistent with intracranial TOD
What is the MOA for fenoldopam?
Dopamine-1 receptor agonist -> vasodilation
Dose: 0.1 μg/kg/min with careful (ie, at intervals of at least 10 minutes) monitoring of BP. The dosage can be titrated up by 0.1 μg/kg/min increments every 15 minutes to the desired SBP, to a maximal dosage of 1.6 μg/kg/min.
No evidence of clinical improvement of AKI in either dogs (0.8 ug/kg/min) or cats (0.5ug/kg/min).
What is the MOA for hydralazine?
Direct smooth muscle relaxant
SSAO (semicarbazide-sensitive amine oxidase) inhibitor.
Interferes with intracellular Ca metabolism. Prevents inititation and maintenance of contractile state in smooth muscle.
Specifically it is thought to interfere with IP3 receptor on SRS.
Dog: 0.1 mg/kg IV over 2 minutes, followed by a CRI of 1.5-5.0 μg/kg/min
Cat: 1.0-2.5 mg per cat SC
What is the main difference between nitroprusside and nitroglycerin?
Nitroprusside: arterial and venous dilators
Nutroglycerin: mainly venodilator
According to ACVIM Consensus Statement, what are the 5 types of cardiomyopathy phenotypes in cats?
1) Hypertrophic cardiomyopathy
2) Restrictive cardiomyopathy
- Endomyocardial form vs Myocardial form
3) Dilated cardiomyopathy
4) Arrhythmogenic cardiomyopathy
5) Nonspecific phenotype
What are the two cardiomyopathy phenotypes that can be caused by hyperthyroidism?
HCM, RCM (restrictive)
What are the staging and definition of cardiomyopathy in cats?
A: Predisposed
B1: Subclinical with low risk of developing CHF/ATE (normal, mild atrial enlargement)
B2: Subclinical with high risk of developing CHF/ATE (moderate, severe atrial enlargement)
C: Current/previous CHF/ATE
D: Refractory CHF
What is the prevalence of HCM in cats?
15%
- 29% in older cats
What is the 5-year cumulative mortality rate in cats with HCM?
23%
What are the breeds that are predisposed to HCM?
Maine Coon, Ragdoll, British Shorthair, Persian, Bengal, Sphynx, Norwegian Forest cat, Birman
According to ACVIM Consensus Statement, in cats with HCM, what are the markers of increased risk of CHF/ATE?
Gallop sound or arrhythmia on PE
Moderate to severe LA enlargement
Decreased LA fractional shortening (LA FS%)
Extreme LV hypertrophy
Decreased LV systolic function
Spontaneous echo-contrast or intracardiac thrombus
Regional wall thinning with hypokinesis
Restrictive diastolic filling pattern
True or False: Dynamic left ventricular outflow tract obstruction (DLVOTO) is a poor prognostic indicator in HCM cat.
False
True or False: A loud systolic murmur (grade 3-4/6) is more common in cats with HCM than in normal cats, but an increase in heart murmur intensity over time does not necessarily indicate the presence or worsening of disease.
True
What is the recommended treatment for cat with stage B1 HCM?
None
What is the recommended treatment for cat with stage B2 HCM?
thromboprophylaxis (e.g. clopidogrel; 18.75 mg/cat PO q24h, with food)
- If patient has rapid ventricular rate or AF → Diltiazem, atenolol or sotalol
What is the recommended treatment for cat with stage C HCM?
Diuretic
Thromboprophylaxis
Pimobendan may be considered if patient has poor contractility and absent of DLVOTO (or dobutamine CRI)
What is the recommended Torsamide dose in cats with CHF?
0.1-0.2 mg/kg PO q24h
True or False: According to ACVIM Consensus Statement, thrombolytic treatment is not recommended in cats with ATE.
True
In human, what is the definition of pulmonary hypertension?
PAP ≥ 25mmHg at rest
What is Bernoulli Equation?
Pressure gradient = 4 x velocity^2 (m/s)
How do you estimate PAP with echo?
Patient needs to have tricuspid regurgitation
Right atrial pressure + Pressure gradient
What peak tricuspid regurgitation velocity make the probability of PH intermediate?
3.0 - 3.4 m/s
According to ACVIM consensus statement, if you want to call the PH is secondary to left-sided heart disease, what are the two additional criteria?
1) Evidence of left-sided heart disease
2) Unequivocal LA enlargement
What are the 6 classification of PH in dogs?
1) Pulmonary arterial hypertension
2) Left-sided heart disease
3) Respiratory disease, hypoxia or both
4) Emboli/thrombus/thromboembolism
5) Parasitic disease (e.g. heart worm)
6) Multifactorial or unclear mechanism
What are the two breeds that are predisposed to PH secondary to interstitial lung diseases?
West Highland White Terriers
Pekingese dogs
According to ACVIM consensus statement, if the PH is secondary to LHD, the use of phosphodiesterase 5 inhibitors (PDE5i) is not recommended as first line treatment.
True
What is the MOA of sildenafil?
It is a phosphadiesterase type 5 inhibitor. Phosphadiesterase type 5 can degrade cGMP to 5’-GMP and decrease the NO vasodilatory function. By inhibiting cGMP degradation, it leads to vasodilation.
True or False: Pimobendan is an PDE5 inhibitor.
False
Pimobendan is a PDE3 inhibitor
What is an example of cause of forward heart failure?
DCM
What is an example of cause of backward heart failure?
degenerative valve disease
What kind of cardiac dysfunction can doxorubicin cause?
Systolic failure/dysfunction (DCM phenotype)
- toxic damage to the mitochondria of cardiomyocytes
How to measure vertebral heart size (VHS)? What is normal reference in dogs and cats?
Compare the sum of cardiac long axis and short axis with vertebral lengths, starting at the cranial border of T4
Dog: < 10.7
Cat: < 8
List 4 causes of mechanical systolic dysfunction.
- Subaortic stenosis
- Hypertrophic obstructive cardiomyopathy
- Acute mitral regurgitation secondary to ruptured chordae tendineae
- DCM
List 3 causes of mechanical diastolic dysfunction.
- HCM
- Cardiac tamponade
- Tachyarrhythmias
What is the common histopathologic of endomyocarditis?
Neutrophilic inflammation
Fibroplasia
How often is SAM detected in cats with HCM?
65%
What is the normal end-diastolic thickness of the interventricular septum or left ventricular posterior wall?
< 6mm
Which PE parameter is a prognostic indicator in FATE?
Hypothermia
In dogs with CHF, what is the definition of diuretic resistance?
furosemide dose > 8mg/kg/d
According to a recent study which level of hypochloremia was associated with poorer prognosis and diuretic resistance in dogs with CHF?
Cl <103.5 mmol/L
How does furosemide enter the renal tubule?
Because of a high degree of protein‐binding to albumin, furosemide is not filtered at the glomerulus, but rather is secreted from the blood into the proximal renal tubule by organic anion transporters.
- NSAIDs can compete with these transporters, hypoalbuminemia can affect the transport
** once furosemide is transported into the nephron lumen, it must remain free of protein interactions so that it can bind to the NKCC transporters on the luminal side of the tubular epithelial cells of the loop of Henle. Diseases such as protein‐losing nephropathies can impair the availability of furosemide to bind to these transporters.
Describe how to measure Vertebral left atrial score and what is the normal range in dogs?
1) Draw a line from the centro-ventral carina to the most caudal aspect of left atria where it intersects with dorsal border of caudal vena cave on the lateral view.
2) Transport the line to the cranial edge of T4 vertebral body.
VLAS ≥ 3 → likely heart failure
What is the cutoff of VLAS to diagnose dog with stage B2 MMVD?
VLAS ≥ 2.5 (sensitivity 100%)
VLAS ≥ 3 (specificity 100%)
Reference:Mikawa S, Nagakawa M, Ogi H, Akabane R, Koyama Y, Sakatani A, Ogawa M, Miyakawa H, Shigemoto J, Tokuriki T, Toda N, Miyagawa Y, Takemura N. Use of vertebral left atrial size for staging of dogs with myxomatous valve disease. J Vet Cardiol. 2020 Aug;30:92-99.
In Doberman Pinscher, what kind of protein deficiency is a common cause for their DCM?
calstabin-2
What value of cTnI is linked with an increased off of sudden death in Dobbermans with DCM?
> 0.34 ng/mL
DCM in Doberman dogs prevalence and responsibel genetic mutation
prevalence is 45-63%
2 genetic mutation:
- pyruvate dehydrogenase kinase 4
- titin
List other breeds apart from Doberman dogs that are known to have genetic predisposition for developing DCM
- Great danes
- Irish wolfhound (secondary to primary congenital rhythm defect)
- Standard poodle, Portuguese Waterdog, Toy Manchester Terrier (juvinile onset of DCM)
describe biphasic clinical progression of DCM with clinical signs
Biphasic because composed by occult and clinical phase
Occult no overt clinical signs but can see increase in N-pro-BNP (Dobbermans).
Cinical phase starts with increased frequency of VPCs or APCs, then AF, S3 sound and left apical murmur indicating dilation of valvular anulus and mitral valve regurgitation
In Doberman Pinscher with DCM, What are the two poor prognostic indicators?
Atrial fibrillation
Bilateral CHF
PROTECT study
In Dobermans in the occult phase of DCM treatment with pimobendan delayed onset of clinical signs by 9 months and increased survival time by 3 months
In Boxer, what kind of protein deficiency has been associated with the cause for their ARVC?
Striatin
What is the common ECG findings in Boxers with ARVC?
Morphology of LBBB on lead I, II, III and aVF
What kind of cardiomyopathy is typical of Golden Retrievers?
Muscular dystrophy due to dystrophin defect (x-linked inheritance)
What are the two medications commonly used in Boxer ARVC treatment?
Sotalol (1.5-3 mg/kg PO q12h)
Mexiletine (5-8mg/kg PO q8h)
What can cause nutritional DCM?
Taurine and L-carnitine deficiency
Also Dalmatian fed low protein diet for urate crystal.
What are the two main neurohormonal pathways involved in the CHF pathogenesis?
RAAS
SNS
- Others: natriuretic peptides, endothelin, vasopressin systems
Is endothelin a vasoconstrictor or vasodilator?
Vasoconstrictor
In the pathogenesis of CHF, what is the main counterregulatory system?
Natriuretic Peptide system
Atrial natriuretic peptide (ANP) & B-type natriuretic peptide (BNP)
List 3 factors that stimulate endothelin production and 3 factors that inhibits endothelin production.
Stimulation: shear stress, angiotensin II, epinephrine, vasopressin, thrombin (all the bad things causing vasoconstriction)
Inhibition: NO, atrial natriuretic peptide, prostacyclin, bradykinin, cGMP
True or False: Endothelin 1 alters normal calcium cycling within muscle cells and is directly toxic to myocardiocytes.
True
For concentric and eccentric hypertrophy, which is pressure overload and which one is volume overload?
Concentric hypertrophy: pressure overload
Eccentric hypertrophy: volume overload
What is the function of phospholamban?
It is a SERCA inhibitor
List 4 mechanisms of abnormal calcium handling during CHF development.
1) Myosin isoform switching
2) Impaired Ca2+ transients and ryanodine function
3) Phospholamban upregulation
4) SERCA downregulation
What is the definition of P mitrale and P pulmonale?
P mitrale: P wave width >40 msec
- Usually seen in LA enlargement
P pulmonale: P wave height >0.5 mV
- Usually seen in RA enlargement
True or False: In CHF management, mixed vasodilator theoretically provides both diuretic and inotrope effects
True
What are the 4 criteria of cardiac remodeling in stage B2 MMVD?
- Grade 3/6 systolic heart murmur
- La:Ao ratio in right-sided short axis view in early diastole ≥ 1.6
- Breed-adjusted VHS > 10.5
- Left ventricular internal diameter in diastole, normalized by weight (LVIDDN) ≥ 1.7
According to ACVIM consensus statement, at which stage of MMVD should the treatment be initiated?
Stage B2
What is the recommended furosemide CRI rate for CHF?
0.66 - 1 mg/kg/hr
Role of urinary Na as a prognostic factor in CHF
Low UNa after furosemide = longer O2 dependency and higher likelihood of diuretic resistance
Nutritional management of cardiac cachexia
at least 60kcal/kg, high protein content, low Na content, possible supplementation of K and Mg especially if on high doses of diuretics or on digoxin
Describe the 7 mechanisms of blunt cardiac trauma
- impact in end-diastole (max ventricular filling) or end systole (max atrial filling)
- sudden increase in pre-load due to abdominal or peripheral vessels compression
- bidirectional forces compressing the heart
- acceleration/deceleration forces
- blast injury
- concussion
- cardiac penetration
Describe 6 possible cardiac injuries
- myocardial rupture
- septal injury (immediated or delayed due to extensive necrosis)
- pericardial laceration (can lead to secondary cardiac herniation and strangulation or PPDH)
- valvular rupture (most vulnerable when closed, so mitral/tricuspid when systole vs aortic/pulmonic in diastole)
- myocardial contusions (haemorrhagic, necrotic - arrhythmogenic due to re-entry circuit formation - severity of arrhythmia proportional to kinetic force applied to myocardium)
- commoto cordis (cardiac impact during ventricle repolarization - ST segment - R on T phenomenon - ventricular tachycardia - immediate death - no histopathological changes)
What are the three most common arrhythmias reported after canine myocardial injuries?
- premature ventricular contractions
- ventricular tachycardia
- nonspecific ST segment elevation or depression
True or False: ECG abnormalities commonly are delayed in onset for up to 48 hours after blunt chest trauma.
True
After myocardial injury, when is the earliest time the cTnI can be detected in the circulation? And how long does it last?
4-6 hr
7 days
What are the most telling signs indicating possible myocardial blunt injury in a polytrauma patient?
ECG abnormalities and/or cTnI >0.11 ng/mL
Hospitalise and close monitoring for 48h telemetry
What is the dose (including CRI) for procainamide?
2-4 mg/kg
10-40 mcg/kg/min
Procainamide
class Ia antiarrhythmic and K channel blocker
prolongation of AP and depression of conduction velocity –> pro-arrhythmic due to possible re-entry mechanism
More effective than lidocaine in controlling VT in humans
In boxers with ARVC proven to decrease VPCs but not syncopal events.
Can trigger SLE
What is normal volume for pericardial effusion?
0.25 ml/kg
Most common causes of pericardial effusion in dogs ad cats
Dogs:
- neoplastic
- idiopathic
Cats:
- CHF
- FIP
Most common clinical manifestation of pericardial effusion?
- vomit (51%)
- if acute = drop of CO
- if chronic = increase venous pressure
True or False: chemodectoma in often found in the R atrium and represents up to 61% of neoplastic causes of pericardial effusion
False: HSA is most commonly found in R atrium and represents up to 61% of neoplastic causes of pericardial effusion
Chemodectoma arises from heart base aortic chemoreceptors.
What is pulsus paradoxus?
Left-ventricular output and systemic arterial pressure normally decrease slightly during inspiration.
Pulsus paradoxus is an exaggeration of this normal pressure difference with respirations; patients with pulsus paradoxus exhibit a fall in arterial pressure during inspiration of 10 mm Hg or more.
What is electrical alternance?
Variable hight of QRS due to swinging of the heart MEA as the hearts moves within the pericardial sac with every beat
Is cTnI or N-pro-BNP elevated in pericardial effusion cases?
N-pro-BNP is not increased as both atria and ventricle are not distended (they are actually compressed).
cTnI is elevated in HSA cases and a cut-off of 0.25 ng/mL is 81% sensitive and 100% specific vs cTnI is WNL in idiopatic cases.
What are the 5 causes for pericardial effusion?
Trauma
Neoplasia
Idiopathic
Coagulopathy
Infectious
True or false: mesothelioma can be very difficult to diagnose and can be mistaken for idiopathic cause
True: shedded neoplastic mesothelial cells can be difficult to differentiate from inflammatory ones
If not responding to steroids and recurrence then pericardectomy and biopsy should be performed
What is the preferred surgical intervention for pericardiectomy? what is the most serious complication reported? How to minimise risks?
subtotal pericardiectomy is the preferred method as it requires less dissection (below phrenic nerves) than total pericardiectomy and it seems more effective than both thotacoscopic pericardial window and fluoroscopy guided baloon pericardiotomy.
The most severe intra-operative complication is VF - risk can be reduced by using harmonics, minimise heart manipulation, normalise acid-base and lytes status and discontiue any arrhythmogenic drug
What is the difference on CVP waveform between constrictive pericardial disease and cardiac tamponade?
Both will show tall a and c wave.
In constrictive pericardial disease, the y descent will be tall (increased resistance to passive atrial filling)
In cardiac tamponade, the y descent will be almost absent (no flow to the atria as collapsed)
How long of an asystolic pause can cause clinical syncopal episodes?
6-8 seconds
What is the intrinsic ventricular heart rate for cats?
100-140 bpm
What is the intrinsic ventricular heart rate for dogs?
15-40 bpm
Cats affected by III degree AV block are often symptomatic and the etiology usually is secondary to systemic disease
False: cats are rarely symptomatic because the vetricular rhythm is still quite high and III degree AV block is usually due to primary structural heart disease
List the main treatments for bradyarrhythmias
- atropine or glycopyrrolate if vagally mediated
- isoproterenol (beta agonist)
- terbutaline (beta 2 agonist)
- aminophylline (PDEi)
- pacemaker
True or False: all the valves in the heart is supported by chordae tendinae
False
Aortic and pulmonary valves do not have chordae tendinae
What dose the EDPVR imply?
End-diastolic ventricular pressure volume relationship
It implies ventricular compliance
What does ESPVR imply?
End-systolic ventricular pressure volume relationship
It implies inotropic state of the heart
Explain the mechanism of vagal reflex.
The acetylcholine released at the vagal nerve endings
→ Fiber membranes permeability to K+ ↑ ↑ ↑
→ Rapid leakage of K+ out of the conductive fibers
→ Membrane potential more negative
→ Hyperpolarization
What is Bradycardia-tachycardia syndrome?
Periods of paroxysmal atrial tachycardia followed by a temporary failure of the sinus rhythm to resume when the tachycardia abruptly terminates → overdriven suppression
What is Mobitz type I and Mobitz type II AV block?
Mobitz type I: progressive prolongation of PR interval before a complete block
Mobitz type II: unexpected irregular absence of QRS complex after P waves
How long of the PR interval in dogs and cats will be considered first degree AV block?
Dog > 130 msec
Cat > 90 msec
What is atropine response test?
To evaluate if the arrhythmias if vagal-induced
Atropine 0.04 mg/kg IV, the positive response = 50-100% increase in HR
- Side effect: dry mouth, mydriasis, constipation, urinary retention
List most common narrow-complex tachycardias
1) Sinus tachycardia
2) SVT (AV nodal re-entry, AV re-entry, atrial tachycardia)
3) Atrial fibrillation
4) Atrial flutter
What are the two main mechanisms that trigger atrial fibrillation?
- ectopic foci - usually at the junction between pulmonary vein and atrial tissue
- re-entry phenomenon - premature beat starts a local abnormal circuit (wavelet hypothesis)
Explain progression of AF
Initial foci causes paroxysmal AF (starts and stop by itself) –> electrical remodeling –> persistent AF –> atrial fibrosis –> long-standing persistent AF
What are the therapeutic strategies for AF treatment?
- rate control
- rhythm control
No definitive evidence of superiority (AFFIRM study found no difference and RACE study found that rate control had less drug-related side effects)
Rate control often more achievable (especially if underlying cardiac disease/remodelling). Goal HR<160
Beta blockers or CCB.
What is the relationship between rate control and survival in dogs?
Each 10bpm drop = 29% increase in survival
Drug therapy for rate control (AF)
First choice: diltiazem + digoxin
Sotalol not effective by itself but can be combined with diltiazem especially if concurrent ventricular arrhythmia. However, amiodarone might be preferrable as no negative inotropic effect.
Therapy for rhythm control (AF)
Pharmacological cardioversion with amiodarone IV
Synchronized electrical cardioversion with pre-emptive amiodaronization
In a recent paper investigating sudden death in dogs with AF which factors were identified as linked with increase risk?
- young age at diagnosis
- syncopal episodes
- increase LA size
Ventricular arrhythmias were NOT linked with increased risk of SCD
In humans but not in dogs the use of digoxin, anticoagulants, sotalol and amiodarone were linked with increased risk of SCD
What is multifocal atrial tachycardia usually associated with?
Pulmonary disease
What is the emergency treatment for SVT in dogs?
Diltiazem 0.125-0.35 mg/kg slow IV over 2-3 minutes
What type of SVT can the cardioversion covert?
Reentry
*Not automaticity
True or False: Atenolol should be used cautiously in patient with kidney disease due to its renal clearance.
True
What are the three arrhythmogenic mechanisms for ventricular arrhythmias?
- Reentry
- Enhanced automaticity
- Triggered activities
What is the definition of sustained VT?
VT > 30 sec
What are the three most reliable diagnostic criteria of VT?
Atrioventricular dissociation
Fusion beats
Capture beats
- Capture beats: A supraventricular impulse conducting through the normal conduction pathways to the ventricle during an episode of VT or AIVR. The PR interval can be longer than normal.
List cardiomyopathies linked to development of ventricular tachycardia in dogs and cats
Dogs:
- DCM
- subaortic and pulmonary stenosis
- arrhtyhmogenic right ventricular cardiomyopathy (Boxer and English Bulldogs)
- inherited ventricular arrhythmia (GSD)
Cats:
- HCM
- Takutsubo
Arrhythmogenic right ventricular cardiomyopathy
Disease of the desmosome –> fibrosis –> arrhythmogenic foci –> malignant re-entrant ventricular arrhythmias
Inherited ventricular arrhythmias in GSD
triggered activity of the LV Purkinje fibers
very young age (12 w) if surviving >2y self resolving (also called Idiopathic Juvinile Ventricular Arrhythmia - also seen in Rhodesian ridgeback).
Possibly due to abnormal sympathetic system maturation
What is E/A ratio used for?
It is used to evaluate the LV diastolic function
What is normal E/A ratio?
0.8 ≤ E/A ratio < 2
What does this E/A ratio and shape indicate?
Impaired relaxation (grade 1 diastolic dysfunction)
If a patient has known diastolic dysfunction and this is the E/A ratio you see, what does it indicate?
Pseudonormal filling pattern (grade 2 diastolic dysfunction)
Progressive diastolic dysfunction causes LA pressure to rise. The latter increases the pressure gradient between the left atrium and the left ventricle and will act as a driving force to fill the ventricle during early diastole.
If a patient has known diastolic dysfunction and this is the E/A ratio you see, what does it indicate?
Restrictive filling pattern (grade 3 diastolic dysfunction)
A further increase in filling pressure will increase the gradient between the left atrium and the left ventricle during early diastole. The E-wave will become even taller and the A-wave shorter. The E/A ratio will be ≥ 2. In severe forms the A-wave may be so small as to be nearly invisible, and the E/A ratio may reach very high values of 5 or more.
What are the three places that have the highest concentration of L-type Ca channels?
Atria
Vascular smooth muscles
Skeletal muscles
Define chronotropic, dromotropic, inotropic, and lusiotropic.
Chronotropic: HR
Dromotropic: AV conduction
Inotropic: contractility
Lusiotropic: myocardial relaxation
Why does high dose Ca channel blocker cause hyperglycemia?
Pancreatic beta cells have L-type Ca channels
Where do 𝜷1 receptors primary locate?
heart, kidney, adipose tissue
How is esmolol metabolized?
erythrocyte esterases
Why does 𝜷 blocker overdose cause hyperkalemia?
1) Inhibit 𝜷1 receptor at the juxtaglomerular cells → decrease renin release → decrease aldosterone formation
2) Inhibit 𝜷2 receptor on the cells membrane → inhibit Na/K-ATPase → decrease potassium uptake
True or False: Both Ca channel blocker and 𝜷 blocker can inhibit pancreatic insulin release and cause hyperglycemia.
True
For Ca channel blocker and 𝜷 blocker overdose, extracorporeal therapy is an option.
False
They are both high-protein bound and lipophilic (high Vd).
TPE can be an option fo severe cases of CCBs (rebound from tissues can happen and a second cycle might be necessary)
What is the MOA of glucagon being used to treat Ca channel blocker and 𝜷 blocker overdose?
Glucagon can bypass 𝜷 receptors and directly activate Gs protein → activates adenylate cyclase (AC) → converts ATP to cAMP → activates protein kinase A (PKA) → enhancing the release of Ca2+ from the sarcoplasmic reticulum
- Glucagon has inotropic, chronotropic, and dromotropic properties
Which side of the aortic valve are most susceptible to infective endocarditis (ventricular vs aortic)? Which side of the mitral valve are most susceptible to infective endocarditis (atrial vs ventricular)?
Ventricular side of the aortic valve
Atrial side of the mitral valve
What are the two common inciting causes for infective endocarditis?
Subaortic stenosis
Cardiac catheterization procedure
How dose the cardiac valve get infected?
Mechanical damage/Inflammation → disruption of the endothelium → exposed extracellular matrix proteins, thromboplastin, tissue factor → activates coagulation cascade (fibrinogen, fibrin, platelet) → blood clot is formed and can bind bacteria → fibronectin binding triggers endothelial cell internalization and local pro- inflammatory and procoagulant responses → endothelial cell expression of integrins → bind bacterias and fibronectin to the extracellular matrix
Staphylococcus and Streptococcus spp have a specific receptors which make them common organisms for infective endocarditis. What is that receptor?
Microbial surface components recognizing adhesive matrix molecules (MSCRAMMS)
What are the two immune-mediated diseases that are commonly seen with infective endocarditis?
Polyarthritis (75%)
Glomerulonephritis (36%)
In Bartonella infected endocarditis, which valve is primarily involved?
Aortic valve
In infective endocarditis, what is the 4 mechanisms that the bacteria evade the host immune system?
1) Fibrinous vegetative lesion
- Shields bacteria from the blood stream and host defenses
- Provides a barrier for antibiotic penetration
2) Be resistant to platelet bactericidal protein
3) Internalize within the endothelial cells (e.g. S. aureus, Bartonella)
4) Colonize RBC without causing hemolysis (e.g. Bartonella)
What are the three most common pathogens for infective endocarditis?
1) Staphylococcal spp (aureus, intermedius, coagulase positive, and coagulase negative)
2) Streptococcus spp (canis, bovis, and ß-hemolytic)
3) E. coli
What is the most important Bartonella specie causing infective endocarditis in dogs?
Bartonella vinsonii ssp. berkhoffii
What is the common murmur associated with infective endocarditis?
Diastolic murmur
In infective endocarditis, which valve involvement indicates worse prognosis?
Aortic valve
How long is the recommended treatment duration for infective endocarditis?
6-8 weeks
- IV for the first 1-2 weeks
- Higher end of the dose range
True or False: Dogs with Bartonella IE have shorter survival times compared to other organisms.
True
What are the main risk factors associated with higher mortality in infective endocarditis? What factor is associated with survival?
Higher mortality:
1) Aortic involvement (92% mortality at 5 months and 33% in first week)
2) Glucocorticoid administration
3) Thromboembolic event
4) AKI
5) thrombocytopenia
Survival:
1) administration of antithrombotic
Reagan KL, et al. Outcome and prognostic factors in infective endocarditis in dogs: 113 cases (2005-2020). J Vet Intern Med. 2022;36(2):429-440.
What is the suggested cut-off value for cTnI for IE diagnosis? is it sensitive or specific?
> 0.625 ng/mL - it is specific but not sensitive
Could be considered as an additional minor Duke criteria
What is the incidence of thromboembolic events in IE? which are the main risk factors?
Up to 80% on post-mortem
can be sterile or septic and usually involve kidneys, spleen, myocardium, brain or limbs
Risk factors:
- mitral valve involvement
- large vegetative lesion of >1-1.5cm
- growing lesions despite antibiotic treatment
Describe how to perform blood culture.
1) Three or four samples from different puncture sites should be clipped and aseptically prepared (e.g. cephalic vein, lateral saphenous vein, jugular vein)
2) The timing of sample collection should be at trough if patient is already on antibiotics
3)The person who performed venipuncture should wear sterile glove and the 5-10ml of blood should be collected from each site with 30 minutes to 1 hours apart.
4) The blood samples are aseptically put in the sealed vial for aerobic, anaerobic bacteria and Bartonella spp. (special medium BAPGM)
In Modified Duke Criteria, what are the 4 major criteria and 7 minor criteria?
Major criteria
1) Positive echocardiogram - vegetative, oscillating lesion, erosive lesion, abscess
2) New valvular insufficiency
3) More than mild aortic insufficiency in the absence of subaortic stenosis
4) Positive blood culture
≤ 2 positive blood cultures
≥ 3 with common skin contaminant
Minor criteria
1) Fever
2) Medium to large dog (> 15 kg)
3) Subaortic stenosis
4) Thromboembolic disease
5) Immune-mediated disease
Polyarthritis
Glomerulonephritis
6) Positive blood culture not meeting major criteria
7) Bartonella serology ≥1:1024
What is the definitive diagnosis for infective endocarditis according to Modified Duke Criteria? What is possible?
Definitive
1) Histopathology
2) Two major
3) One major + two minors
Possible
1) One major + one minor
2) Three minors
What is normal mean electrical axis (MEA) in dogs and cats?
Dog: +40 - +100
Cat: 0 - +160
What is the difference between cardioversion and defibrillation?
Cardioversion: delivery the energy that is synchronized to the QRS complex
Defibrillation: Asynchronously deliver the energy to terminate the life-threatening arrhythmias
When is the timing to deliver a shock during cardioversion?
The peak of R wave (absolute refractory period)
What is the usual energy dose for cardioversion?
1-2 J/kg
- much lower than emergency defibrillation in which 2-10J/Kg are delivered
Which power source is effective at terminating ventricular fibrillation? AC or DC or both work?
DC
What is the main complications of cardioversion?
V fib
What are the 2 most common ways to perform temporal pacing? Mention all the other ones as well
Transvenous and transcutaneous are the most commonly used ones.
Other ones:
* Transesophageal
* Transthoracic
* Epicardial
* Manual (thoracic thump)
What is happening? How to fix?
This is a failure to capture pacemaker issue - pacemaker spike not followed by qrs.
Adjust output (amplitude/time) to achieve threshold.
What is the MOA for Digoxin?
1) positive inotropic (by inhibiting Na-K ATPase → increased intracellular Na → increased intracellular Ca
2) Decreased AV conduction: vagomimic effect
In which subset of patients can digoxin be particularly useful?
Patients in AF with concurrent left ventricular dysfunction which makes them intolerant to beta-blockers and diltiazem
Digoxin has significant inotropic effect which switches off RAAS (decreased after load)
Which are the main factors/drugs that can interfere with digoxin efficacy?
- P-glycoprotein inhibitors: P-glycoprotein is an efflux pup that mediates secretion of digoxin in the kidneys, liver and gut. Amiodarone, quinidine, diltiazem, cyclosporine and itraconazole inhibit P-glycoprotein, therefore enhance digoxin toxicity risk and a dose reduction should be considered
- hyperkalaemia reduces digoxin binding affinity with Na/K ATPase
- hypermagnesemia and hypercalcaemia enhances calcium overload in the sarcoplasmic reticulum and increase the risk of spontaneous cardiac depolarization (VPCs)
Why does hypokalemia increase the risk of digoxin toxicity?
digoxin binds at the K site of Na-K ATPase
During hypokalemia, there are not that many potassiums competing with Dogoxin → increased toxicity
Main manifestations of digoxin toxicity
cardiac: early toxicity showing with VPCs, then any type of atrioventricular block, then supraventricular tachycardia and ventricular fibrillation
GI: mesenteric ischemia due to excessive smooth muscle contraction
Why is it important to measure serum concentrations of digoxin?
High serum digoxin levels have been associated with increased mortality even without overt signs of toxicity
Possible treatments for digoxin toxicity
- activated charcoals to reduce further GI absorption
- atropine administration to reduce PNS-induced bradycardia
- correct electrolyte abnormalities
- digoxin-fab antibodies (ovine so possible anaphylaxis - use only in severe cases)
What are the three subunits of cardiac troponin and what are their functions?
Cardiac troponin T: bind to tropomyosin and secure it to the thin filament
Cardiac troponin I: inhibitory the hydrolysis of ATP → inhibit myosin and actin interaction
Cardiac troponin C: binding site for calcium to remove the blockage of filament interaction
What is the normal value of cTnT and cTnI respectively?
cTnT is tightly bound to actin, so its level should not be detectable in health vs cTnI < 0.05 ng/mL
Which troponin subunit is not a good biomarker for myocardial injury. Why?
Troponin C, because the skeletal and myocardium have very similar isoforms
Are troponin intracellular or extracellular protein?
Intracellular protein
If there is myocardial injury, how soon can the elevated cardiac troponin to be detected?
2-3 hours after injury
peak at 18-24 hours
There are two pools for cardiac troponin, which are structural pool and cytosolic pool, which one contains the majority of troponin at normal state?
Structural pool
After a cardiac insult, which cardiac troponin will have higher concentration in the circulation, troponin I or T?
Troponin I
What are the 6 mechanisms of troponin release?
Dying cells
- Necrosis
- Apoptosis
- Cell turnover
Viable cells
- Increased permeability
- Formation of vesicles
- Increased proteolysis
What are the two breeds that inherently have higher cTnI concentration?
Boxers
Greyhounds
What are the two proposed pathways for troponin elimination? Why is it relevant?
Reticulo-endothelial system
Renal clearance
It is advised to interpret increases in troponin very carefully in patients with renal impairment
True or False: Troponins have limited value in diagnosing primary heart diseases.
True
True or False: Critically ill patients with noncardiac disease often have higher troponin concentrations than patients with severe primary cardiac disease.
True
Non-cardiac myocardial injury > primary cardiac diseases
Is an increased cTnI concentration a useful prognostic factor in critically ill patients?
Yes for dogs and humans but not cats.
In dogs critically ill patients have 4x the odds for poorer outcomes and longer hospitalisation stay if increased troponin. cTnI also increased APPLE score specificity without compromising sensitivity.
List 4 diseases in which an increased troponin was linked with a poorer outcome
GDV, parvovirosis, sepsis and Babesiosis
True or False: CTnI can be elevated in dogs with renal diseases.
True
What are the three conditions that may enhance lidocaine’s antiarrhythmic effect?
1) acidic environment
2) increased extracellular K+ concentration
3) partial depolarized cells
Which class of antiarrhythmics does lidocaine belong to?
IB
How is mexiletine metabolized?
renal excretion
What are the different effect on QT interval between IA, IB and IC antiarrhythmic drugs?
IA (moderate): cause QT prolongation
- Because it cause moderate blockade of the rapid component of the delayed rectifier K+ current
IB (weak): cause QT shortening
IC (strong): no effect on QT interval
What is the MOA of 𝜷-blocker as antiarrhythmic agent?
𝜷-receptors are Gs-coupled protein receptors. Inhibition = drop CAMP = reduced activity of HCN (CAMP dependent) of funny current) and closing of L-type Ca channels –> Inhibit funny current –> drop HR
Is Esmolol 𝜷1 or 𝜷2 blocker?
𝜷1
Is Atenolol 𝜷1 or 𝜷2 blocker? How is it eliminated?
𝜷1, excreted by kidney
Is Sotalol 𝜷1 or 𝜷2 blocker?
It is K channel blocker and also non-selective 𝜷 blocker
How dose Class I antiarrhythmics work?
Sodium channel blocker,
Slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, reduces conduction velocity.
Why does sotalol have less negative inotrope effect than propanolol?
Because sotalol is also a K channel blocker → AP prolongation allows more Ca to enter the cell
Which two classes of antiarrhythmics can slow AV nodal conduction?
Class II (beta blockers) and IV (Ca channel blockers) –> work on AV node cells
What is the MOA of pimobendan? (4 mechanisms)
-
Phosphodiesterase III inhibitor –> increased intracellular CAMP –> increased PKA activity –> increased phosphorylation of phospholamban –> inhibition of SERCA –> more Ca available (increased lusitropy)
Also increased CAMP opensa Ryanodine-bound Ca channel and L-type Ca channel (increased inotropy) - Calcium sensitizing effect (increased cTNc affinity for Ca)
- active metabolite inhibits A1 adenosine receptor (Gi coupled receptor) –> increased contractility
- arterio-venous dilatory effect due to phosphorilation (inactivation) MLCK
Troponin and acidosis
In acidosis status troponin affinity for Ca++ is severely decreased.
This is why pimobendan is a very good drug choice.
Main advantages of pimobendan over dobutamine
- no increase in oxygen demand
- no increase in PAP
- still effective in respiratory acidosis
Additional pharmacologic effects of pimobendan
- anti-inflammatory (inhibition of ngkB and less iNOs)
- blunts sympathetic response
- antithrombotic effect with decrease TXA release by platelets
- insulinotropic effect via calcium sensitization
Can pimobendan be given to patients with renal impairment?
Yes mainly hepatic metabolism with <5% being excreted via renal route
EPIC study
stage B2
at day 35 decreased LVESd and LA/Ao also increased time to CHF development and cardiac-related death
What are the two major categories of congenital heart diseases?
1) Shunting defect
2) Perivalvular defect
What is a PDA?
Communication between Aorta and Pulmonary artery
What is the most common cause of congenital right-to-left shunt in dogs?
Tetralogy of Fallot
What is Tetralogy of Fallot composed of?
Ventricular septal defect (VSD)
Overriding aorta
Pulmonary stenosis
Right ventricular hypertrophy
N.B. RV hypertrophy is secondary to “Eisenmenger physiology”. Initially L to R shunt due to interventricular septal defect, but due to pulmonary stenosis and high pressure on R side the shunt reverts to R to L
True or False: tetralogy of Fallot causes central cianosis vs PDA causes peripheral cianosis
True: tetralogy with R–> L shunt due to interventricular septal defect causes cianosis in the whole body vs PDA associated with pulmonary hypertension R–> L shunt distal to the origin of the left subclavian artery (after the major branches to the head and upper extremities have been given off) –> cianosis only in the caudal half of the body
What is the equation for palliative phlebotomy in patient with congenital heart disease and polycythemia? What is the cut-off to perform palliative phlebotomy? What is the target in ER textbook?
Volume of the blood remove = body weight x blood volume x (Current PCV-Desired PCV)/Current PCV
*Blood volume: 90 ml/kg (dog); 70 ml/kg (cat)
Cut-off: 70%
Target: 60%
What are the three electrolyte imbalance and one endocrine disease that can potentiate digoxin toxicity?
1) Hypokalemia
2) Hypomagnesemia
3) Hypercalcemia
4) Hypothyroidism
What kind of ECG change indicates procanamide toxicity?
25% prolongation of QRS complex
True or False: The antiarrhythmic effect of Procanamide is increased by high potassium and decreased by low potassium.
True
- Hyperkalemia strongly enhances procainamide-induced conduction slowing by increasing the interaction between the drug and sodium channels during the rested phase of the cardiac cycle
What is the formula to calculate fraction shortening? What is considered normal in dogs and cats?
FS (%) = (LV internal diameter at end-diastole - LV internal diameter at end-systole)/LV internal diameter at end-diastole
Normal
- Dog: 25-45%
- Cat: 31-75%
Amiodarone mechanisms of action
Class III but mechanisms encompassing all classes of anti-arrhythmic
List 3 side effects of amiodarone.
1) Hepatic toxicity
2) Thyroid dysfunction
3) Arrhythmias
What is a specific dermatological complication from spironolactone in cats?
Ulcerative facial dermatitis
True or False: Hypothermia is a poor prognosis indicator in cats with ATE.
True
A rectal temperature of< 37.1C (98.9°F)has been shown to predict a < 50% survival probability (in ER textbook)
In dogs with heartworm infection, which pulmonary artery does the adult worms most often found?
Right caudal lobe artery
Describe the current canine heartworm treatment guidelines
Day 1:
- Start on prednisone 0.5 mg/kg BID x 1 week, then 0.5 mg/kg SID x 1 week, then 0.5 mg/kg EOD x 2 weeks (if symptomatic)
- Start Doxycycline 10 mg/kg BID x 4 weeks
- Start macrocyclic lactone (i.e. ivermectin, milbemycin, moxidectin, and selamectin) to kill immature forms of heartworm
Day 30:
- Re-apply macrocyclic lactone (i.e. ivermectin, milbemycin, moxidectin, and selamectin) to kill immature forms of heartworm
Day 31-60:
- A one-month wait period following doxycycline before administering melarsomine is currently recommended as it is hypothesized to allow time for the Wolbachia surface proteins and other metabolites to dissipate before killing the adult worms.
Day 61:
- Apply macrocyclic lactone (i.e. ivermectin, milbemycin, moxidectin, and selamectin) to kill immature forms of heartworm
- Melarsomine 2.5 mg/kg IM
- Start on prednisone 0.5 mg/kg BID x 1 week, then 0.5 mg/kg SID x 1 week, then 0.5 mg/kg EOD x 2 weeks
- STRICT cage rest
Day 90:
- Apply macrocyclic lactone (i.e. ivermectin, milbemycin, moxidectin, and selamectin) to kill immature forms of heartworm
- Melarsomine 2.5 mg/kg IM
- Start on prednisone 0.5 mg/kg BID x 1 week, then 0.5 mg/kg SID x 1 week, then 0.5 mg/kg EOD x 2 weeks
- STRICT cage rest
Day 91:
- Melarsomine 2.5 mg/kg IM
- Strict cage rest for 6-8 weeks
Day 120:
- Test for microfilaria
Day 360:
- Antigen test 9 months after last melarsomine injection
- screen for MF
- If still Ag positive, re-treat with doxycycline followed by two doses of melarsomine 24 hours apart
This protocol has shown 100% negativization within 1y of diagnosis (vs only 2 doses of melarsomine or long term moxidectin without melarsomine)
What does HARD stand for?
Heartworm Associated Respiratory Disease - typical of cats - severe inflammatory response in the lungs mimicking asthma
Why is doxycycline included in heartworm treatment?
To treat Wolbachia which is a symbiotic gram negative bacteria harboured by D. Immitis. It can significanlty worsen the inflammatory response triggered by D. Immitis.
What is Kussmaul’s sign?
Paradoxical rise in right atrial pressure (or right jugular venous pressure) during inspiration → decreased RV compliance for various reasons
What is isoproterenol?
Non-selective 𝜷 adrenergic agonist
For the temporary pacemaker, what does VVI mode?
Three letter system:
V (chamber paced) V (chamber sensed) I (abiltiy to inhibit activity when intrinsic heart beat sensed)
Permanent pacers also have a fourth letter indicating if the generator can change rate of firing according to patient’s activity level
What is the difference between atrial fibrillation and atrial flutter?
Atrial fibrillation: irregular atrial contraction
Atrial flutter: regular but very rapid atrial contraction (atrial rate of 300 bpm with ‘saw tooth’ appearance and a atrial:qrs ratio of 2:1)
What is the main energy source for cardiomyocytes?
Fatty acid
Does a tube that is too compliant cause overdamping or underdamping during arterial blood pressure monitoring?
Overdamping
What is the vascular effect of D1 and D2 receptors?
D1 (post-synaptic): vasodilation
D2 (pre-synaptic): inhibit NE release from sympathetic nerve ending → less vasoconstriction
Is dopamine receptor a G protein-coupled receptor or voltage-gated receptor?
G protein-coupled receptor
What is the MOA of ephedrine?
increase the release of NE from sympathetic nerve ending
Of the two determinants of arterial blood pressure—cardiac output and vascular resistance, which one is the main determinant of blood pressure?
Vascular resistance
How does anemia cause vasodilation?
1) Decreased blood viscosity → increased flow velocity —> increased shear stress → increased NO production → vasodilation
2) less Hb —> less NO scavenging
Does ACEI decrease preload or afterload?
Both
Preload: decreased sodium and water retension
Afterload: vasodilaiton
Does ACEI cause arterial or venous dilation?
Both
Does Calcium channel blocker cause arterial or venous dilation?
Arterial
Does hydralazine cause arterial or venous dilation?
Both
Why ACEI cause hyperkalemia?
Inhibit aldosterone
What type of drug is prazosin?
Competitive post-synaptic 𝜶1 receptor antagonist
True or False: Aldosterone is pro-inflammatory and pro-fibrotic.
True
Aldosterone is considered proinflammatory and profibrotic and causes endothelial dysfunction secondary to vasoconstriction and vascular remodeling.
True or False: Renin can be release when its 𝜷 adrenergic receptors are stimulated.
True
What are the 5 functions of angiotensin II?
1) Increase aldosterone
2) Increase ADH
3) Cause vasoconstriction
4) Increase thirst drive within hypothalamus
5) Increase Na-H exchange at the proximal renal tubules
What are the two types of AGII receptors?
AT1 - mediates vasoconstriction
AT2 - mediates vasodilation, antifibrotic, antiproliferative and natriuretic effects (counterbalance)
What does a multimodal approach to RAAS suppression include?
- ACEi
- ARBs
- Aldosterone antagonist
What was the conclusion of the BESST trial?
Benazepril + spironolactone»_space;> benazepril alone
What is the potential adverse effect when giving sodium nitroprusside to a patient with hepatic disease?
Cyanide toxicity
Sodium nitroprusside oxidizes sulfhydryl groups present in erythrocytes and cell membranes or reacts with hemoglobin to produce methemoglobin. This reaction results in the production of nitric oxide (as well as five cyanide groups), which leads to direct vasodilation through the action on vascular smooth muscle. Free cyanide is converted to thiocyanate by either thiocyanate oxidase within erythrocytes or a transsulfuration reaction with thiosulfate by the rhodanese enzyme in the liver.
What do ESPVR and EDPVR imply?
ESPVR (End-systolic pressure volume relationship) - ventricular compliance
EDPVR (End-diastolic pressure volume relationship) - contractility
Types of adenosine receptors, mechanism of action and location
A1 - myocardial nodal tissue - Gi coupled (decreased HR)
A2 - smooth muscle - Gs coupled (vasodilation)
A3 - mast cell - inflammatory cytokines (important in lungs as they cause vasoconstriction and asthma)
How do the venous function curve and the cardiac function curve in: venodilation/venoconstriction, volume load/volume depletion, decrease/increase contractility, arteriole dilation/constriction
How does the PV loop change with changes in preload?
How does the PV loop change with changes in contractility
How does the PV loop change with changes in afterload?
In an ECG with a speed of 25mm/sec 5 boxes = …
50 mm/sec 10 boxes = …
1 second
In a standard 25 mm/sec recording count QRS in 30 boxes = 6 seconds and multiply by 10 to obtain HR
Wiggers diagram with aortic stenosis
Wiggers diagram with mitral stenosis
Wiggers diagram with aortic regurgitation
Wiggers diagram with mitral valve regurgitation
Where is norepinephrine synthesized and how
Adrenal medulla and sympathetic nerve terminals
From L-tyrosine –> L-dopa –> dopamine –> norepinephrine –> epinephrine
What is the rate limiting step for norepi synthesis?
Thyrosine hydroxylase
What are the main types of norepinephrine receptors? where are they located respectively?
Junctional (or post-synaptic)
Pre-synaptic
Extrajunctional (binds to circulating norepi synthesised by adrernal medulla)
what is the name of th eenzyme metabolising free norepinephrine after it has interacted with junctional receptors?
Catecol-o-metyltransferase
What is the main function of pre-synaptic receptors for norepi?
negative feedback –> free norepi will bind to them and they will inhibit further norepi release
How many adrenoreceptor types are recognised? List them
alpha 1 (a, b, d)
alpha 2 (a/d, b, c)
beta 1
beta 2
beta 3
Gprotein type for each adrenoreceptor
alpha 1 Gq
alpha 2 Gi
beta Gs
alpha 1
junctional
mainly mediate vasoconstrction with exception of alpha 1a which has inotropic effect on heart (NE>E)
alpha 1a and 1d vasoconstriction large arteries
alpha 1b vasoconstriction of smaller arteries and vascular hypertrophy (big role in development of systemic hypertension)
alpha 2
mainly extrajunctional
mediate vasoconstriction (E>NE)
exception for alpha 2 a/d vasodilation (located on epithelium and pre-synaptic membrane)
cellular mechanisms of alpha 2a/d presynaptic receptor
when norepi binds, Ca channel close, while K channel open –> hyperpolarization –> no more norepi release
mechanism for alpha 2a/d vasodilation
located on endothelial cell and increase relase NO
what happens with the coronary arteries during sympathetic stimulation?
alpha 1a vasoconstriction –> increase tone to counteract collapsibility due to increased HR and contractility
beta 2 –> vasodilation
Anyway overall the coronary perfusion is mainly under metabolic control not SNS
In general alpha 1 has more affinity for norepi vs alpha 2 for epi
True
Beta 1 and beta 2 have more affinity for norepi
False
beta 2 E»>NE (this is why it is such a good bronchodilator)
beta 1 E= NE
What is the function of beta 3 receptors?
As a safety measure agains sympathetic overstimulation beta1 and beta 2 receptors are internalised after stimulation, however if excessive stimulation beta 3 are Gi and will inhibit further increase in chronotropy and inotropy
Explain internalization process after beta 1 and beta 2 stimulation
Both are Gs coupled –> PKA will phosphorylate beta-ARK protein which will uncople beta receptors and stimulate endocytosis. once recptor is in the vesicle it can either be recycled or degraded. Some internalised receptor bind to arrestin and start pathway that facilitate cardiac hypertrophy.
Fill in the following table
List the non-hemodynamic effects of catecholamines
- increase BG (beta 3 on adipose tissue increase lipolysis, beta 2 on hepatocytes increase gluconeogenesis and glycogenolysis, alpha 2 in pancreas decrease insulin and increase glucagon secretion)
- increase lactate
- increase oxygen consumption
decrease potassium
increase plt activity (alpha 2 receptors with release of ADP, serotonin and TXA) - increased mitochondrial uncoupling and oxidative stress
- immunoparalysis
How do alpha 2 agonist cause hypothermia?
act on noradrenergic neurons in the hypothalamus responsible for thermoregulation
What is milrinone?
PDI3 inhibitor used for vasodilation and decrease afterload in cardiac failure patients
Renal elimination so very careful in CKD
Which vasopressor can’t be used in a peripheral access?
dobutamine and vasopressin
high risk of severe tissue necrosis
all other vasopressor safe (if extravasation use phentolamine to reverse)
What is the Bezold-Jarish reflex?
Sinus bradycardia, hypotension and vasodilation triggered by stimulation of baroreceptors and chemoreptors in the LV due to excitement, coughing, vomiting, serotonin, etc.
Also known as vaso-vagal response.
List 3 manifestations of sinus node dysfunction
- sinus arrest
- sinus block
- sick sinus syndrome
What’s the difference between sinus block and sinus arrest?
Sinus arrest is the failure of generating impulse and involve P cells of the SA node vs sinus block is the failure of propagating the impulse and it is a dysfunction of T cells
Which breeds are associated with sick sinus syndrome?
Old Schnauzers and Terriers
Laplace’s law for LV hypertrophy
LV wall stress = (LV pressure x LV radius) / LV thickness
In order to reduce LV wall stress LV radius needs to be reduced or LV thickness needs to increase
is phenoxybenzamine selective alpha 1 antagonist? what about prazosin?
Prazosin in selective alpha 1 antagonist while phenoxybenzamine is not and that’s why phenoxybenzamine is preferred as a treatment for pheochromocytoma
Why is labetalol a good choice for patients undergoing cavectomy and adrenalectomy?
It is both alpha and beta blocker, therefore there is vasodilation without compensatory tachycardia
Mechanism of action for methyled xanthines (i.e. theophylline, caffeine)
non-selective PDEi
Describe the structure of potassium channels
quaternary protein(each type has a signature AA sequence) with a central pore in the intracellular side and selectivity filter on the extracellular side
List the major classes of potassium channels
- KATP (vasodilatory shock)
- KCa (NO action)
- Kv (voltage gated)
- Kir (inward rectifying)
- K2p (tandem pore domain - always open - ‘leaky channels’ - stabilise resting membrane potential)
Diazoxide mechanism of action
open Katp channels –> allow K exit –> more negative intracellular environment –> ca channel close – > no relase of insulin
Used as part of insulinoma treatment
Why do we measure N-pro-BNP and not BNP? What is the difference between BNP and ANP?
N-pro-BNP is produced in a 1:1 ratio with BNP and it is much more stable, so suitable for sampling and measurement
ANP is only produced by atria vs BNP also by ventricle - they are both produced secondary to stretch stimulation
N-pro-BNP test interpretation
Dogs with MMVD and a N-pro-BNP >1500 pmol/L more likely to develop overt CHF in the following 3-6 months
Dobermans >5y and N-pro-BNP >450 pmol/L high risk to develop DCM (even when still in occult phase)
List myocarditis causes
- Infectious: viral (parvo, FIV, distemper), protozoal (Chagas disease by Tripanozoma cruzi), bacterial (Lyme disease, Bartonella, septicaemia), fungal and parasitic (Toxo and Neospora)
- Toxic (doxorubicin with >250mg/m2 - irreversible damage)
- Traumatic
- Other (radiation, heat stroke, catecholamine toxicity)
Doxorubicin toxicity in cardiomyocytes
Irreversible myocyte damage due to increased expression of autophagy receptors on myocytes membranes.
Seen most often with doses of >250mg/m2
What is the most common cause of left atrial rupture?
Jet lesion due to MMVD regurgitation (velocities up to 5m/s hitting the atrial tissue >100 times a minute)
How to diagnose atrial rupture?
Often clot seen in pericardial sac but also:
- LA/Ao >1.6
- Mitral regurgitation jet occupying >50% LA
- PE
- cardiac tamponade
Why is phenoxybenzamine preferred to phentolamine in pheochromocytoma treatment?
They are both non-selective alpha antagonists, but phenoxybenzamine binds to receptor irreversibly (changes shape) so it provides reliable long-term blockade vs phentolamine more rapid onset of action (more severe reflex tachycardia) and shorter duration as it a competititive reversible antagonist.
Definition of cardio-renal syndrome in human medicine
‘A disorder affecting the heart or the kidney whereby acute or chronic disturbances of one organ cause detrimental effects on the other’
What is the equivalent of cardio-renal syndrome in veterinary medicine and why the terminology is different
consensus in calling it cardiovascular-renal disorders (CVRDs) to highlight the role of vasculature in the pathogenesis of this complex disorder
CVRDs classification
CVRDh (primary heart)
CVRDk (primary kidney)
CVRDo (secondary to systemic disease i.e. sepsis or concurrent primary heart and primary renal conditions)
these can be further differentiated into stable or unstable
General approach to CVRDs
- perform early investigations of the heart in patients with renal impairment and investigate kidney disease in instances of heart dysfunction
- patients with heart disease should be treated with the lowest effective dose of diuretic to preserve renal health
- prompt identification and treatment of SHT in renal patient
- titrate drug dosage according to current ability of renal clearance (especially those with narrow therapeutic margin i.e. digoxin)
- ensure adequate nutrition to avoid cardiac and renal cachexia
Definition of hemodynamic coherence
Successful resuscitation of both micro and macrocirculation
List two instances when hemodynamic coherence is lost
- unstable macrocirculation but stable microcirculation –> continue fluid resuscitation and if not successful consider vasopressor
- stable macrocirculation but unstable microcirculation –> more IVFT is not going to help and llikely detrimental
Typical of sepsis/sirs
Explain possible causes and relative consequences of loss of hemodynamic coherence
Severe inflammation leads to:
- loss of glycocalix and endothelial integrity
- induced rigidity of RBC and inability to release vasoactive ADP
- increased iNOS.
Consequences:
- decreased O2 delivery to tissues due to tissue oedema and decreased microcirculatory flow
- heterogeneous perfusion
List methods for monitoring peripheral tissue perfusion
- NIRS (near-infrared light to penetrate tissues and measures the absorption and scattering of these wavelengths by hemoglobin, myoglobin, and cytochromes, providing information on tissue oxygenation)
- microcirculation visualisation with dark-field microscopy
- thermography
- cutaneous laser doppler
- regional capnography
- transcutaneous O2 and CO2 monitoring
Simply describe cardiopulmonary bypass circuit
Venous cannulation used to drain patient’s blood into a reservoir –> heat and gas exchanger –> blood pumped back to patient via arterial cannulation
Therapeutic hypothermia applied to decrease metabolic rate of tissues
What is cardioplegia in the context of CPB
It is a cold, pressure-controlled, hyperkalemic solution injection into the aortic root or coronary sinus which induces diastolic arrest
List key points of post-op CBP management
- often patients have negative IVF balance
- manage hemostatic derangements
- manage common lytes imbalances (hypokalemia, hypocalcemi, hypomagnesemia and hypernatremia)
- avoid hyperglycaemia (insulin administration when BG >10mmol/L)
- analgesia
- 24h of antibiosis
- continue heparin for 10 days post op and antiplatelet for 90 days
- cardiac medications usually discontinued as issue surgically resolved but pimobendan could still be beneficial in supporting myocardiac recovery and reverse myocardia remodelling
List most common post CBP complications
- Thromboembolic events
- Coronary spasm
- Hypotension
- Surgical site failure
- Haemorrhage
- ARDS
- AKI
- Arrhythmias
- Immunocompromise
What is the difference between pH STAT and Alpha STAT approach in metabolic management of CBP patients?
In the pH Stat approach, the high pH due to hypothermia (decreased metabolic rate and slower CO2 dissociation into H+ and HCO3-) is corrected by adding CO2 –> this leads to improved cerebral perfusion but higher risk of embolism.
In Alpha Stat approach the pH is not corrected, this might lead to brain vasoconstriction but less risk of embolism.
No difference in outcomes when body temp >28C. For temp <28 pH stat best during cooling while alpha stat best during rewarming.
List and briefly describe Rummel torniquet and Pringle manouver
These are two hemostatic techniques.
Rummel tourniquet uses umbilical tape placed underneath a vessel while the two upper ends get through a piece of tubing. Pull the ends protruding from tubing and clamp them to occlude the vessel.
Pringle manouver puts pressure on both hepatic artery and portal vein via the epiploic foramen
Dobutamine in cats
Higher risk of arrhythmias
Definition of cardiogenic shock and mainstay of therapy
State of end-organ hypoperfusion due to the heart’s inability to deliver sufficient oxygen to tissues to meet metabolic demands in the presence of adequate intravascular volume.
Name two non-invasive methods to estimate CO
- Bioimpedance
measures resistance to electric current to the thorax which is proportional to aortic flow - Bioreactance
measure the phase shift (change in frequency of current applied to thorax) –> delay in phase shift = increase in CO
Bioimpedance not reliable in dogs vs bioreactance accurate but no clinical applications in dogs so far
Is this patient likely to be fluid-responsive?
Yes, it Y descend on the CVP waveform is very prominent.
In human a Y descend >4mm has been correlated to patients operating on the flat portion of the FS curve
What is the Kussmaul sign? What does it mean?
A fluid-responsive patient should have a decrease in CVP during inspiration, if that doesn’t occur it is an indication of possible fluid overload and it is called Kussmaul sign
What percentage of dogs with Angiostrongylus have PH?
Up to 40%
Associated with poorer prognosis in the first 6months post diagnosis
