Unit 3 - CV A&P Flashcards
how are myocytes similar to neural & skeletal tissue
- generate RMP
- can propagate an AP
- contain contractile elements arranged in sarcomeres
- have T-tubules
RMP is established by what 3 mechanisms
- chemical force
- electrostatic counterforce
- Na/K-ATPase
3 things unique to cardiac muscle (vs. skeletal and neural)
- joined by intercalated discs
- gap junctions
- consume a lot of O2 at rest - 8-10 mL O2/100g/min (contain a lot more mitochondria)
what is the purpose of gap junctions in cardiac muscle
facilitate spread of cardiac AP through myocardium
why do myocytes consume a lot more O2 at rest vs. skeletal muscle cells
contain more mitochondria
what is equilibrium potential?
situation where there’s no net movement of an ion across a cell membrane
equation used to predict an ion’s equilibrium potential
Nernst equation
what is automaticity
ability to generate AP spontaneously
how do cardiac conduction cells display automaticity
when they set HR (normally SA node)
what is excitability
ability to respond to an electrical stimulus by depolarizing & firing AP
what is conductance
ability to transmit electrical current
what is inotropy
force of myocardial contraction during systole
what is chronotropy
heart rate
what is dromotropy
conduction velocity through the heart (velocity = distance/time)
lusitropy
rate of myocardial relaxation during diastole
what is RMP?
an electrical potential across a cell membrane at rest
what eletrolyte is continuously leaked by nerve cells at rest
K+ (loses positive charge)
what is the primary determinant of RMP?
K+
increased : RMP more negative
decreased: RMP more positive
what is threshold potential
voltage change that must occur to initiate depolarization
what is the primary determinant of threshold potential
calcium
how does calcium affect threshold potential
decreased serum Ca2+ = TP more negative
increased calcium = TP more positive
what is depolarization
movement of a cell’s membrane potential to a more positive value (less difference between inside and outside of cell)
what happens to HR as distance between threshold potential & RMP narrows
increases bc myocardial cells reach threshold faster
what is the all or none phenomenon
once depolarization starts, it cant be stopped
what determines the ability to depolarize
difference of RMP & TP
how does the difference in RMP & TP affect depolarization
RMP closer to TP = easier to depolarize
RMP further from TP = harder to depolarize
what happens after depolarization in excitable tissue
action potential
what is repolarization
return of cells RMP to more negative value after depolarization
what causes cell repolarization?
when K+ leaves the cell or Cl- enters the cell
when is the cell resistant to subsequent depolarization
refractory period
what is hyperpolarization
movement of a cell’s membrane potential to a more negative value beyond baseline RMP
can a hyperpolarized cell be depolarized?
it’s more difficult bc RMP is further from TP
2 purposes of Na-K-ATPase
- removes Na+ that enters cell during depolarization
- returns K+ that left cell during depolarization
for every ___ Na+ ions removed by Na-K-ATPase, ____ K+ ions are brought in
3 Na
2 K
restores ionic balance towards RMP in excitable tissue
Na-K-ATPase
positive inotropic drug that inhibits Na-K-ATPase
digoxin
is Na-K-ATPase active or passive transport?
active transport - requires energy in the form of ATP
how does hypokalemia affect RMP/TP
- RMP more negative
- cells more resistant to depolarization
how does hyperkalemia affect RMP
- more positive
- cells depolarize more easily
how does hypocalcemia affect RMP/TP
- TP becomes more negative
- cells depolarize more easily
how does hypercalcemia affect RMP/TP
- TP more positive
- cells more resistant to depolarization
what happens to Na+ channels in severe hyperkalemia
- inactivated
- channels arrest in closed-inactivated state
how does cardioplegia solution work
- high levels of K+; cells can’t repolarize, Na+ channels locked
- arrests heart in diastole
why does IV calcium reduce the risk of dysrhythmias in hyperkalemic patients
increases the gap between RMP and TP
why is depolarization longer in myocytes vs. neurons
AP has a plateau phase - depolarization prolonged
do SA and AV nodes have a plateau phase?
nope
5 phases of myocyte AP
- depolarization
- initial repolarization
- plateau
- final repolarization
- resting phase
what part of EKG tracing reflects depolarization
Q wave
which phase of myocyte AP reflects Na+ in
depolarization
electrolyte movement during initial repolarization phase of myocyte AP
Cl- in
K+ out
electrolyte movement in final repolarization phase of myocyte AP
K+ out
part of EKG tracing that corresponds with final repolarization phase of myocyte AP
T wave
during which phase of myocyte AP is the EKG isoelectric
resting phase
electrolyte movement during resting phase of myocyte AP
K+ out
Na/K-ATPase function (K+ leak)
part of EKG wave that corresponds with plateau phase of myocyte AP
ST segment
electrolyte movement during plateau phase of myocyte AP
Ca2+ in
K+ out
threshold potential at myocyte depolarization
-70 mV
what counters loss of K+ ions to maintain depolarized state in plateau of myocyte AP
activation of slow voltage-gated Ca2+ channels
transmembrane resting potential of myocytes
-90 mV
purpose of K+ leak channel open in resting phase of myocyte AP
maintains transmembrane resting potential
order of normal cardiac conduction
SA node - internodal tracts - AV node - bundle of His - L/R bundle branches - Purkinje fibers
how many phases involved in SA node AP
3 (no phase 1 or 2)
3 phases of SA node AP
spontaneous depolarization
depolarization
repolarization
electrolyte movement during spontaneous depolarization of SA node
- Na+ in
- Ca2+ in (T-type)
electrolyte movement during depolarization phase of SA node AP
Ca2+ in (L-type)
what is the “funny current” in SA node AP and why is it called that?
- at the end of repolarization (MP about -60 mV), ion channels open that conduct slow depolarizing currents
- initiates phase 4 depolarization
- called “funny” bc it’s activated by hyperpolarization, not depolarization
- abbreviated I-f
events that occur in spontaneous depolarization of SA node myocytes
- Na+ enters cell progressively, making it more positive
- at -50 mV, transient Ca2+ channels open (T-type) to further depolarize cell
what causes depolarization in SA node myocytes
Ca2+ entry via voltage-gated calcium channels (L-type)
(T-type calcium channels close)
events that occur during repolarization of SA node conduction tissue
- K+ channels open, K+ exits cell making it more negative
- K+ efflux = repolarization, return of phase 4
what happens to calcium channels during repolarization of SA node
L-type Ca2+ channels close, Ca2+ conductance decreased
what 2 things determine heart rate
- intrinsic rate of dominant pacemaker (usually SA node)
- autonomic tone
intrinsic firing rates of SA, AV, and purkinje fibers
SA = 70-80
AV = 40-60
purkinje = 15-40
where does the SA node reside
right atrium
what determines the intrinsic rate of SA node firing
the rate of spontaneous phase 4 depolarization of SA node
how do volatiles affect SA node
depress SA node automaticity - can cause junctional rhythm
why is a junctional rhythm slow and without a P wave?
disease or hypoxia impairs SA node’s ability to function as dominant pacemaker - cells with next highest rate of spontaneous phase 4 depolarization assumes as pacemaker
responsible for SNS tone
cardiac accelerator fibers (T1-T4)
responsible for PNS tone
CN 10 (vagus)
what 3 variables can be manipulated to change the sinus node rate
- rate of spontaneous phase 4 depolarization
- threshold potential
- RMP
3 situations that can increase HR and reach threshold potential faster
- slope of phase 4 depolarization increases
- slope of phase 4 remains constant but TP becomes more negative
- slope of phase 4 remains constatnt but RMP becomes less negative
how does more negative threshold potential affect HR
shorter distance between RMP and TP - cells reach threshold faster
how does SNS affect HR
NE stimulates beta-1 receptor, increases HR by Na+ and Ca2+ conductance
increases rate of spontaneous phase 4 depolarization
how does PNS affect HR
ACh stimulates M2 receptor - slows HR by increased K+ conductance, hyperpolarizing SA node
how does PNS affect RMP
decreases - reduced slope of spontaneous phase 4 depolarization
oxygen delivery calculation
DO2 = CO x [(hgb x SaO2 x 1.34) + (PaO2 x 0.003)] x 10
equation for O2 carrying capacity
(Hgb x SaO2 x 1.34) + (PaO2 x 0.003)
what is CaO2
O2 carrying capacity
tells us how many grams of O2 are contained in a dL of arterial blood
what happens to HR if the distance between threshold potential and resting potential narrows?
HR will increase because myocardial cells will reach treshold faster
current that’s responsible for spontaneous phase 4 depolarization in SA node?
I-f
primary determinant of the pacemaker’s intrinsic HR
I-f current (sets the rate of spontaneous phase 4 depolarization)
expected oxygen delivery in a 70 kg adult
1,000 mL/min
expected CaO2 in 70 kg adult
20 mL/O2/dL
expected VO2 (oxygen consumption) in 70 kg adult
250 mL/min
expected CvO2 (venous oxygen content) in 70 kg adult
15 mL/dL
solution coefficient for dissolved oxygen
0.003
body extraction ratio
EO2 = 25%
how to calculate MAP using Ohm’s law
MAP = (CO x SVR / 80) + CVP
what are the flow, pressure gradient, and resistance factors of blood pressure?
- flow = CO
- pressure gradient = MAP - CVP
- resistance = SVR
primary determinant of vascular resistance
radius of arterioles
used to predict if flow will be laminar or turbulent
Reynold’s number
Reynold’s number that will predict if flow will be laminar, turbulent, or transitional
- laminar: Re < 2,000
- turbulent: Re > 4,000
- transitional: Re = 2,000 - 4,000
2 possible assessment findings when there’s turbulent flow
vibrations can cause a murmur (valve disease) or bruit (stenosis)
what is viscosity the result of
friction from intermolecular forces as fluid passes through a tube
what determines viscosity
- Hct
- body temp
relationship between blood viscosity and temperature
inversely related
how does saline dilution improve flow when giving PRBCs
decreases Hct
what 2 factors determine EDV (Preload)
- filling pressures
- compliance
what 2 factors determine ESV
- afterload
- contractility
what 2 factors determine stroke volume
- EDV (preload)
- ESV
determinants of CO
- HR
- SV
determinants of MAP
- CO
- SVR
determinants of tissue blood flow
- MAP
- local vascular resistance
determinants of O2 delivery
- tissue blood flow
- CaO2
normal CO in adult
5-6 L/min
cardiac index calculation & normal values
CO/BSA
2.8-4.2 L/min per m^2
stroke volume calculation & normal values
EDV - ESV or CO x 1000/HR
50-110 mL/beat
stroke volume index calculation & normal values
SV/BSA
30-65 mL/beat per m^2
ejection fraction calculation & normal values
(EDV - ESV / EDV) * 100 or (SV/EDV) * 100
60-70%
MAP calculation & normal values
(1/3 x SBP) + (2/3 x DBP) or (COxSVR /80) + CVP
70-105 mmHg
amount of oxygen dissolved in blood (PaO2) follows what law
Henry’s
flow is directly proportional to what 2 factors
- vessel radius
- arteriovenous pressure difference
flow is inversely proportional to what 2 factors
- viscosity
- length of tube
what are the 5 components of Poiseuille’s law
- Q - blood flow
- R - radius
- △P - arteriovenous pressure gradient
- n - viscosity
- L - length of tube
how much more flow occurs when the radius of a tube is quadrupled?
256x
pulse pressure calculation & normal values
SBP - DBP
(stroke volume output / arterial tree compliance)
40 mmHg
normal SVR
800-1500 dynes x sec x cm-5
SVR index calculation & normal values
(MAP-CVP / CI) x 80
PVR calculation & normal values
(MPAP - PAOP / CO) x 80
150-250 dynes x sec x cm-5
PVR index calculation & normal values
(MPAP - PAOP / CI) x 80
250-400 dynes x sec x cm-5 per m^2
functional unit of the contractile tissue in the heart
sacromere
amount of tension each sarcomere can generate is directly related to:
number of cross-bridges that can be formed before contraction
what is preload
ventricular wall tension at the end of diastole just before contraction
(the volume that returns to the heart during diastole)
how does A-fib affect preload
loss of atrial kick = reduced preload
how does venous tone affect preload
decreased tone (sympathectomy) = decreased preload
how does valvular regurgitation affect preload
aortic or mitral regurg increase preload
illustrates the relationship between ventricular volume and output
ventricular function curve
what is the Frank Starling mechanism
increased ventricular volume produces a larger CO up to the plateau, after which additional volume overstretches sarcomeres, decreases # cross-bridges that can be formed, and decreases CO
commonly used as a surrogate for ventricular volume
filling pressure
how is ventricular volume measurement obtained
TEE
3 surrogate measures of LVEDV
- LVEDP
- LAP
- PAOP
x and y axis of ventricular function curve
measurement of ventricular volume
PAOP
relates ventricular volume to ventricular output
Frank starling mechanism
terms that can be used on the y axis of Frank Starling curve
- CO
- SV
- LVSW
- RVSW
(ventricular output)
terms that can be used on x axis of Frank Starling curve
filling pressures:
- CVP
- PAD
- PAOP
- LAP
- LVEDP
EDV:
- RVEDV
- LVEDV
ability of myocardial sarcomeres to perform work (shorten & produce forece)
contractility
reflects ventricular output for given EDV
contractility
atrial contraction = ____% of final LDEDV & CO
20-30%
why does CO usually decrease in A fib
loss of atrial kick, which contributes 20-30% of final LDEDV & CO
why is a non-compliant ventricle more dependent on well-timed atrial kick to fill ventricle & generate SV
ventricle is stiff
patients more likely to experience a decreased CO with cardiac rhythm disturbances like A-fib or a junctional rhythm?
patients with decreased ventricular compliance: hypertrophy, diastolic failure (preserved EF), fibrosis, aging
how do most meds increase or decrease contractility
alter amount of calcium available to bind to myofilaments or impair sensitivity of myocardium to calcium
5 things that increase contractility
- SNS stimulation
- catecholamines
- calcium
- digitalis
- PDE inhibitors
how does hypercapnia affect contractility
decreases
how do hyperkalemia and hypocalcemia affect contractility
decrease
how do volatiles affect contractility
decreases
2nd messenger in the myocardium
calcium
primary substance that determines contractility
calcium
action that opens voltage-gated L-type Ca2+ channels in the myocyte
depolarization of T-tubule
what results in activation of RyR2 in the myocyte
influx of calcium
what stimulates cross-bridge formation and causes myocardial contraction in the myocyte
calcium binds to troponin C (Tnc)
what causes myocardial relaxation in the myocyte
calcium unbinds from troponin C (Tnc)
how is most calcium returned to sarcoplasmic reticulum
SERCA2 pump (ATP-dependent)
once inside the SR, what does calcium bind to
storage protein called CSQ (calsequestrin)
how is some calcium removed from the myocyte
Na+-Ca2+ exchange pump (NCK)
what determines the duration of myocyte contraction?
action potential duration
restores RMP in myocyte
Na/K-ATPase
what happens to the myocyte if RMP increases to a level that exceeds a level of normal repolarization
voltage-gated Na+ channels can’t fire and get stuck in closed-inactive state
3 ways beta-1 receptor stimulation modulates calcium in the myocyte
- activation of L-type calcium channels
- stimulation of ryanodine 2 receptor to release more calcium
- stimulation of SERCA2 pump to increase calcium uptake
how does beta-1 stimulation in the myocyte affect PKA?
activates AC - converts ATP to cAMP - increases PKA activation
normally inhibits SERCA2 activity
phospholamban (PLN)
net effect of beta-1 stimulation in myocyte
more forceful contraction over a shorter time (positive inotropy) with enhanced relaxation (positive lusitropy) between beats
what is afterload
force the ventricle must overcome to eject its stroke volume
3 factors that decrease stroke volume
- decreased preload
- decreased contractility
- increased afterload
what determines the majority of afterload
SVR (arteriolar tone)
why is the LV thicker than the right?
has to overcome a much higher afterload
what is wall stress in the heart
force that holds the heart together
things that reduce myocardial wall stress
- decreased intraventricular pressure
- decreased radius
- increased wall thickness
what explains why pt with HTN compensates with LVH?
increased wall stress
what is intraventricular pressure
force that pushes the heart apart
wall stress =
(intraventricular pressure x radius) / ventricular thickness
during what part of the cardiac cycle are all 4 valves closed
isovolumetric contraction & relaxation
valves open and closed during ventricular ejection
- mitral closed
- aortic opened
valves open/closed during atrial systole
- open: mitral
- closed: aortic
what valve is open during rapid ventricular filling
mitral
3 events that occur during systole
- isovolumetric contraction
- rapid ejection
- reduced ejection
equation for law of laplace as it relates to the LV?
wall stress = (intraventricular pressure / radius) / ventricular thickness
3 phases of the cardiac cycle assoc. with open mitral valve and closed aortic valve
- rapid ventricular filling
- atrial systole
- diastasis
3 events that occur during diastole
- isovolumetric relaxation
- rapid filling
- reduced filling
4 events that occur between Q wave & end of T wave
- rapid ventricular ejection
- LV systole
- aortic valve opens
- stroke volume
valves open/closed during ventricular ejection
- mitral closed
- aortic open
what causes first heart sound
during isovolumetric contraction, LV pressure > LA pressure and mitral valve closes
phases of cardiac cycle that occur during systole
- isovolumetric contraction
- ventricular ejection
phases of cardiac cycle that occur during diastole
- isovolumetric ventricular relaxation
- rapid ventricular filling
- reduced ventricular filling (diastasis)
- atrial systole
what causes aortic valve to open during ventricular ejecion
LV pressure > aortic pressure
during what phase of the cardiac cycle is SV ejected into aorta
ventricular ejection
when is most SV ejected from LV
first 1/3 of systole
what causes the 2nd heart sound
aortic pressure > LV pressure, aortic valve closes
what happens to LV pressure and volume during isometric ventricular relaxation
LV pressure decreases, volume constant
what does the dicrotic notch represent
onset of aortic valve closure causes a short period of retrograde flow from aorta towards valve, followed by complete termination of retrograde flow upon complete valve closure
required to pump Ca2+ back into sarcoplasmic reticulum
ATP
what causes the mitral valve to open
LA pressure > LV pressure
during what parts of cardiac cycle is mitral valve open
- rapid ventricular filling
- reduced ventricular filling
- atrial systole
when does 80% of LV filling occur
during ventricular filling
what contributes to last 20% of LV filling
atrial kick
the end of atrial systole correlates with:
EDV
what does height measure in a cardiac pressure volume loop
ventricular pressure
what does width measure in a cardiac pressure volume loop
ventricular volume
what do corners measure in a cardiac pressure volume loop
where valves open & close
what does net external work output measure in a cardiac pressure volume loop
myocardial work
what 2 events measured by pressure volume loop occur in systole
isovolumetric contraction
ejection
phases of ventricular pressure volume loop
- ventricular filling (diastole)
- isovolumetric contraction (systole)
- ventricular ejection (systole)
- isovolumetric contraction (diastole)
- ejection
- isovolumetric relaxation
normal LV volume and pressure at the beginning of diastole
volume ~50 mL (ESV)
pressure 2-3 mmHg
net gain during ventricular filling
70 mL
which is greater during isovolumetric contraction: LV pressure or LA pressure?
LV
which is greater during ventricular ejection: LV pressure or aortic pressure
LV
when are DBP and SBP measured via AL waveform
DBP when aortic valve opens
SBP at peak of ejection curve
which is greater during period of isovolumetric relaxation: aortic pressure or LV pressure
aortic
what is ejection fraction
percentage of how much blood is pumped by the heart during each beat
EF values:
- normal
- mild dysfunction
- moderate dysfunction
- severe dysfunction
- normal > 50%
- mild dysfunction 41-49%
- moderate 26-40%
- severe < 25%
what is external work
amount of work the ventricle must do to eject SV
how is external work estimated
multiply SV x mean aortic pressure
2 factors that increase workload of heart
- ventricle accepts increased volume
- ventricle has to generate more pressure to open aortic valve
what happens to pressure volume loop with increased or decreased preload
- increased: gets wider but returns to original ESV
- decreased: gets narrower but returns to original ESV
what happens to ESV with increased contractility
decreases
what happens to pressure volume loop with increased contractility
loop gets wider, taller, & shifts to left
what happens to pressure-volume loop with decreased contractility
loop gets narrower, shorter, shifts to right
pressure volume loop with increased afterload
loop gets narrower, taller, and shifts ESV to the right
pressure volume loop with decreased afterload
loop gets wider, shorter, shifts ESV to the left
where do LCA & RCA arise from
aortic root (sinus of Valsalva)
where does the left coronary artery emerge from
behind pulmonary trunk, divides into LAD and circumflex arteries
what artery divides to form LCA & circumflex arteries
left coronary
what artery perfuses the anterolateral and apical walls of LV and anterior 2/3 of interventricular septum
left anterior descending artery
what does the circumflex artery supply
LA and lateral/posterior walls of LV
what perfuses the RA, RV, interarterial septum, and posterior 1/3 of interventricular septum
right coronary
perfuses inferior wall of LV
posterior descending artery
(RCA)
the origin of which vessel defines coronary dominance
posterior descending artery
what gives rise to posterior descending artery in 70-80% of patients
RCA (right dominance)
what is it called if the circumflex artery gives rise to the posterior descending artery
left dominance
what is it called when the RCA supplies the PDA
co-dominance
where does SA node receive blood supply from in ~70% of patient?
where is it received from in remaining population?
RCA
circumflex
where does the AV node receive blood supply from in ~80% of patients
RCA
what perfuses the bundle of His in ~75% of patients
LCA
what almost exclusively supplies the right and left bundle branches
LCA
4 main components of coronary venous circulation
which coronary artery do they run along
- great cardiac vein (LAD)
- middle cardiac vein (PDA)
- anterior cardiac vein (RCA)
- coronary sinus
where is the coronary sinus located
posterior aspect of RA just superior to tricuspid
where does blood returning to coronary circulation from LV drain?
coronary sinus
what is cannulated to admin retrograde cardioplegia during CPB
coronary sinus
how does blood returning from RV empty directly into RA
anterior cardiac veins carry bypass coronary sinus and go directly to RA
small amount of blood empties directly into all 4 cardiac chambers via:
thebesian veins
how does adenosine affect coronaries
causes vasodilation
how does hypocapnia affect coronaries
causes vasoconstriction
what 2 pressures determine coronary perfusion pressure
aortic DBP - LVEDP
3 epicardial vessels
- RCA
- LAD
- CxA
what provides majority of coronary vascular resistance
coronary arterioles
how does muscarinic stimulation affect coronaries
cause coronary vasodilation
how does histamine-2 activation affect coronary circulation
causes coronary vasodilation
how does histamine-1 activation affect coronary circulation
causes coronary vasoconstriction
which myocardial arterial bed is most susceptible to ischemia
endocardial blood vessels of the myocardium
what area of the LV does lead I monitor
lateral
biploar leads & what they monitor
I - lateral LV (circumflex artery)
II - inferior LV (RCA)
III - inferior LV (RCA)
limb leads and what they monitor
aVR
aVL - lateral LV (circumflex artery)
aVF - inferior LV (RCA)
precordial leads and what they monitor
V1 - septum (LAD)
V2 - septum (LAD)
V3 - anterior (LAD)
V4 - anterior (LAD)
V5 - lateral (circumflex)
V6 - lateral (circumflex)
best TEE view for diagnosing LV ischemia
2nd best view?
midpapillary muscle level in short axis
2nd - apical segment in short axis
supplies oxygenated blood to the myocardium
left and right coronaries
normal coronary blood flow
225-250 mL/min or 4-7% of CO
myocardial O2 consumption and extraction ratio at rest
8-10 mL/min/100g with extraction ratio of ~70%
coronary blood flow =
coronary perfusion pressure / coronary vascular resistance
coronary blood flow is autoregulated between at what MAP?
between ~60-140 mmHg
autoregulation of coronary flow is a net effect of what 3 things
- local metabolism
- myogenic response
- ANS
what is coronary blood flow dependent on at a MAP < 60 or > 140
coronary perfusion pressure
how do coronary vascular resistance or LVEDP affect coronary blood flow
anything that increases resistance or LVEDP can decrease coronary blood flow
most important determinant of coronary vessel diameter
local metabolism
byproduct of ATP metabolism & potent coronary vasodilator
adenosine
how does the coronary endothelium react to increased MvO2
- releases adenosine and a variety of other vasodilators (NO, PGs, hydrogen, K+, CO2) to increase blood flow
how does vasodilation affect coronary perfusion
increases
refers to a vessel’s innate ability to maintain a constant vessel diameter
myogenic response
myogenic response when coronary vessel diameter increases
tendency to contract
myogenic response to coronary vessel diameter decrease
tendency to dilate
times when ANS effects prevail over products of local metabolism to affect coronary vascular tone
Prinzmetal angina (vasospastic myocardial ischemia) - overactive coronary alpha receptors can cause intense chest pain at rest
how does endocardial beta-2 stimulation affect the coronaries
- increases cAMP
- decreases MLCK sensitivity to Ca2+
- results in coronary vasodilation
what is the difference between coronary blood flow at rest and maximal dilation
coronary reserve
allows coronary flow to increase in times of HD stress or exercise
coronary reserve
coronary reserve in patients with atherosclerotic vessels and increased O2 demand
vessels may be maximally dilated at rest and unable to dilate further
decreased coronary reserve
what happens to flow through LCA during ventricular systole
greatly diminished
what happens to flow through RCA throughout cardiac cycle
remains relatively constant
what happens to endocardial vessels during myocardial contraction
dramatically reduced flow during systole d/t mass of LV
why can’t the RV occlude it’s blood supply during systole
doesn’t generate a high enough pressure
myocardial O2 consumption at rest
consumes ~70% of the O2 delivered to it
normal coronary sinus O2 sat
~30%
what must happen to satisfy increased myocardial O2 demand
- coronary blood flow and/or CaO2 must increase
- heart can’t meaningfully increase its extraction ratio when O2 demand increases
contributes to perception of chest pain during ischemia
lactic acid production (r/t anaerobic metabolism)
4 things that decrease coronary blood flow and in turn decrease myocardial O2 supply
- tachycardia
- decreased aortic pressure
- decreased vessel diameter (spasm, hypocapnia)
- increased LVEDP
2 things that decrease CaO2 and myocardial O2 delivery
- hypoxemia
- anemia
2 things that cause decreased O2 extraction and myocardial O2 delivery
- L shift of hgb dissociation curve (decreased P50)
- decreased capillary density
how does increased HR affect myocardial O2 supply and demand
decreases O2 supply while increasing demand
how does EDV affect myocardial O2 demand
decreased EDV reduces wall stress and decreases demand
how does aortic DBP affect myocardial O2 supply
decreased aortic DBP = decreased coronary perfusion pressure = decreased O2 supply
3 circumstances that affect both sides of the myocardial O2 delivery/demand equation
- changes in HR
- aortic DBP
- preload
when is the LV best perfused
during diastolic filling time
how does diastolic filling time affect myocardial O2 supply
shorter time = less time to deliver O2 to LV = decreased supply
usually unaffected by tachycardia, well-perfused throughout cardiac cycle
RV
how does increased aortic DBP affect myocardial O2 supply
increases pressure that perfuses coronaries and increases supply
how does increased aortic DBP increase both myocardial o2 supply and demand
- supply: increases pressure that perfuses coronaries
- demand: increases wall tension and afterload
how does increased preload affect myocardial supply and demand
- supply: increased EDV = dec coronary perfusion pressure = dec supply; increased LVEDP decreases coronary perfusion pressure and decreases supply
- demand: increased wall stress = increased demand
when do most perioperative MIs occur
24-48 hours following surgery
what is regulation of vascular smooth muscle tone dependent on?
successful integration of ANS, RAAS, local metabolism, myogenic response
which electrolyte plays a critical role in regulation of peripheral vessel diameter
calcium
as a general rule, how does calcium affect vascular smooth muscle tone
increased calcium = vasoconstriction
decreased calcium = vasodilation
3 important pathways that affect intracellular calcium
- G-protein cAMP pathway (vasodilation)
- NO cGMP pathway (vasodilation)
- PLC pathway (vasoconstriction)
how does the G-protein cAMP pathway affect vascular smooth muscle tone
- in vascular muscle cells, increased PKA = decreased intracellular calcium
- results in vasodilation
how does PKA affect excitation-contraction coupling
- inhibits voltage gated calcium channels in sarcolemma
- inhibits calcium release from SR
- reduces sensitivity of myofilaments to calcium
- facilitates calcium reuptake into SR via SERCA2 pump
things that decrease NO production
- ACh
- substance P
- bradykinin
- serotonin
- VIP
- thrombin
- shear stress
6 steps in NO cGMP pathway leading to vasodilation
- NOS catalyzes conversion of L-arginine to NO
- NO diffuses from endothelium to smooth muscle
- NO activates GC
- GC converts GTP to cGMP
- inc. cGMP reduces intracellular calcium and causes smooth muscle relaxation
- PDE5 deactivates cGMP to guanosine monophosplate
activators of PLC pathway
- phenylephrine
- NE
- AT2
- endothelin-1
how does angiotensin II receptor activation lead to vasoconstriction
Gq G-protein stimulated = PLC = IP3 & DAG = increased calcium = vasoconstriction
PLC activation increases production of what 2 second messengers
IP3 & DAG
effects of increased IP3 & DAG production in vascular smooth muscle
- IP3: augments calcium release from SR
- DAG: activates PKC
- opens voltage-gated calcium channels in sarcolemma
- increases calcium influx
how does iNO affect vascular smooth muscle
increases cGMP = reduced intracellular calcium = pulmonary vasodilation
decreased PVR, decreased RV afterload
inactivates iNO
hemoglobin
why doesn’t iNO cause hypotension
inactivated before entering systemic circulation
phenylephrine stimulates what effector to ultimately cause vasoconstriction
PKA
in which phase of ventricular AP is conductance greatest for:
- Cl-
- K+
- Na+
- Ca2+
- Na+ conductance greatest in phase 0
- Cl- conductance greatest in phase 1
- Ca2+ conductance greatest in phase 2
- K+ conductance greatest in phase 3
3 things that cause SA node to increase firing rate
- increased slope of spontaneous phase 4 depolarization
- TP more negative
- RMP more positive
what causes SR to release calcium
when calcium stimulates RyR2 receptor
what is calcium-induced-calcium release
calcium activates RyR2 receptor, which causes large quantities of calcium to be released from SR
variables to describe x axis of frank starling curve
Filling pressures or EDV
- filling pressures: CVP, PAD, PAOP, LAP, LVEDP
- EDV: RVEDV, LVEDV
variables to describe y axis of frank starling curve
ventricular output:
- CO
- SV
- LVSW
- RVSW
2 conditions that set afterload proximal to systemic circulation
aortic stenosis
coarctation of aorta
which region of the heart is most susceptible to ischemia? why?
LV subendocardium
best perfused during diastole
- as aortic pressure inc. LV tissue compresses its own blood supply
- compression + decreased coronary flow during systole = increased coronary vascular resistance, predisposed to ischemia
how does PNS stimulation affect HR
slows HR via increased K conductance (hyperpolarizes SA node)
how much of CO does the myocardium receive at rest?
5% (~225 mL/min)
most potent vasodilator released by cardiac myocytes
adenosine
how does increased preload affect coronary O2 supply and demand
increased demand
decreased supply
decreases the supply of oxygen to the myocardium by increasing LVEDV, which in turn decreases CPP.
how does increased preload affect coronary O2 suply and demand
increased demand
decreased supply
decreases the supply of oxygen to the myocardium by increasing
LVEDV, which in turn decreases CPP.
how does increased preload affect coronary O2 suply and demand
increased demand
decreased supply
decreases the supply of oxygen to the myocardium by increasing
LVEDV, which in turn decreases CPP.
