Coronary circulation Flashcards
Where to the coronary arteries arise from?
the root of the aorta behind the right and left cusps of the aortic valve
What do the coronary arteries supply?
entire myocardium
right supplies right atrium and ventricle
left supplies left atrium and ventricle
What coronary artery is dominant?
right 50%
left 20%
both about 30%
what do the microcirculatory coronary vessels consist of?
terminal arterioles
precapillary sinuses
capillaries
venules
what are cardiomyocytes surrounded by?
capillaries that are aligned with them
what is the average length of a microcirculatory?
about 350um
During diastole, what do precapillary sinuses serve as?
blood reservoir
During systole, what do precapillary sinuses do?
disgorge the blood to sustain myocyte perfusion
How does most blood of the blood return after passing through the capillary beds?
to right atrium through coronary sinus
some through anterior coronary veins
What are the three vascular communications between vessels of the myocardium and cardiac chambers?
arteriosinusoidal
asterioluminal
thebesian vessels
What happens to the small arteries in ateriosinusoidal channels as they enter the chambers?
they lose their arterial structure and divide into irregular endothelium lines and sinuses that anastomose with other sinuses and capillaries to communicate with cardiac chambers
What are arterioluminal vessels?
small arteries or arterioles that open directly into the atria and ventricles
What are thebesian vessel?
small veins that connect capillary beds and communicate with cardiac and other thebesian veins
- communication through extensive plexus of subendothelial vessels
- do not give significant blood supply
What is the principal factor responsible for myocardial perfusion?
aortic pressure
generated by the heart itself
changes provoke parallel changes in coronary blood flow
What do abrupt changes in aortic pressure produce?
equally abrupt changes in coronary blood flow in the same direction
How is perfusion pressure maintained at a new level?
a return of blood flow toward the level observed before the induced change in perfusion pressure
*autoregulation of blood flow
What is autoregulation in the coronary arteries mediated by?
a myogenic mechanism, metabolic activity, endothelium
What will increased metabolic activity of the heart cause?
Decrease in coronary vascular resistance and a decrease in cardiac metabolism to increase coronary resistance
What is the position of the autoregulatory region affected by?
metabolic state of cardiac muscle
What are changes to coronary blood flow mainly caused by?
calibre changes of coronary resistance vessels in response to metabolic demands of the heart
What is coronary flow reserve?
the difference between maximal flow by vasodilator drugs and the flow in the physiological range
What is extravascular compression?
squeezing effect of the contracting myocardium on blood vessels
*LV hypertrophied = greater compression
When does maximal left coronary inflow occur?
Early diastole when ventricles have relaxed and extravascular compression is virtually absent
What is the flow pattern of the RCA?
similar pattern to left
Because of lower pressure developed during systole by thin right ventricles, reversal of blood flow does not occur in early systole and constitutes a greater proportion of total coronary inflow
What does pacing stress cause?
a rapid switch from lactate uptake to production (seen as a drop in the ST segment)
*rapid reversal upon stopping
What drugs are typically used to treat chest pain?
organs nitrate, and nitrites that do not dilate the coronary vessels selectively
Do organic nitrates/nitrites have an effect on autoregulation?
little
arterioles in the ischemic heart are likely already maximally dilated by the response to symptoms
In a patient with marked narrowing of a coronary artery, what is the result of administration of vasodilators?
fully dilate normal vessel branches parallel to the narrowed segment and reduce the head of pressure to partially occluded vessel
*increase flow to other vessels = decrease in pressure gradient
What is coronary steel?
vasodilator further compromises blood flow to the ischemic myocardium and elicits pain and ECG changes indicative of tissue injury
* observes with dipyridamole
What is the action of dipyridamole?
acts by blocking cellular uptake and metabolism of endogenous adenosine
also decreased or eliminated coronary autoregulation because it dilates small resistance vessels
How do nitrites/nitrates alleviate chest pain?
decreasing cardiac work and MVO2 by relaxing great veins (decreasing preload) and decreasing BP (decreasing afterload)
What must the decrease in pressure work and MVO2 from nitrates/nitrites be greater than?
then the decrease in coronary blood flow and O2 supply consequent to the decrease in coronary perfusion pressure
What do nitrites and endogenous NO do?
dilate large coronary arteries and collateral vessels to increase blood flow to ischemic myocardium and alleviate chest pain
How does the ratio to endocardial and epicardial blood flow change if diastolic pressure in coronary arteries is low?
the ratio falls below one
blood flow to endocardial regions is more severely impaired than epicardial regions
- more damage in the inner wall than outer of the ventricle
What is the decrease in ratio to endocardial and epicardial blood flow reflected as?
an increased gradient of myocardial lactic acid and adenosine concentrations from the epicardium to the endocardium
How does sympathetic nerve stimulation affect coronary blood flow?
increases
In perfused hearts, what is eliminated by cardiac arrest or ventricular fibrillation?
mechanical effects of extravascular compression
The increase in coronary blood flow with sympathetic stimulation is a sum of what factors?
increase in metabolic activity by rate and contraction tends to dilate coronary resistance vessels
What is initially often observed with sympathetic stimulation?
vasoconstriction before vasodilation attributed to metabolic effects
What causes the initial vasoconstriction with sympathetic stimulation?
after B-adrenergic receptors are blocked to eliminate positive chronotropic and inotropic effects, direct reflex activation increases coronary resistance
*The main function of sympathetic nerve fibres is to vasoconstriction
What is the function of A and B adrenergic receptors?
A - constrictors
B - dilators
What control is coronary resistance predominately under?
local nonneuronal control
What does vagus nerve or Ach stimulation cause?
slight dilation of coronary resistance vessels and at a constant perfusion pressure increased coronary blood flow
What is vasodilation initiated by?
muscarinic receptors on endothelial cells that release NO
What occurs when NO synthase is inhibited by L-NAME?
vagal stimulation and Ach are less able to increase coronary blood flow
What is the relationship between myocardial metabolic activity and the magnitude of coronary blood flow?
close parallelism
direct positive
What does a decrease in the ratio of O2 supply to demand cause?
releases vasodilator substances from the myocardium into interstitial fluid, where they can relax coronary resistance vessels
What causes a decrease in the ration of O2 supply to demand?
decrease in arterial blood O2 or coronary blood flow
increase in cardiac metabolic rate
What would a decrease in O2 demand cause?
decrease the release of vasodilator and permit greater expression of basal tone
What are the three key factors that mediate vasodilation?
adenosine
NO
opening of KATP channels
What opens the KATP channels?
a decrease in oxidative metabolism in vascular smooth muscle, decreasing ATP
opening will cause hyperpolarization
What does the hyperpolarization of the KATP membrane cause?
reduces the Ca2+ entry and relaxes the coronary smooth muscle to increase the flow
*prevent Ca2+ overload
and a decrease in ATP that will generate an outward current that decreases AP duration and limits entry of Ca2+ during phase 2 of AP
What signals an increase in NO?
in endothelial cells, hypoxia activates KATP channels that signal an increase in NO to relax vascular smooth muscle
What is through to be an AP role during O2 supply and demand imbalances?
protective role
What does adenosine do at low concentrations?
activate KATP channels and enhance NO release
What would occur if all three key vasodilator substances were inhibited?
coronary blood dlow would decrease at both rest and during exercise
contractile dysfunction and signs of myocardial ischemia become evident
When is most of the O2 in coronary blood flow extracted?
during one passage through the myocardial capillaries
* the O2 supply to myocardial cells is flow limited
What does complete elimination of coronary flow result in?
a quick depletion of high-energy phosphates and accumulation of lactate
also, contractile akinesis occurs over time and evolves into MI and tissue necrosis
What is akinesis?
a particular area is lacking contraction
What does a modest reduction in coronary flow result in?
a decrease in myocardial O2 consumption (~10-50%), a transiently increased dependence on anaerobic glycolysis, oxidative free fatty acids at a decreased rate, and modest to severe contractile dysfunction
What is the classic symptom of MI?
angina pectoris
- chest pain
What causes angina pectoris during ischemia?
high H+ concentration activates NHE and H+ is extruded from cells in exchange for Na+
ischemia inhibits Na+ K+ ATPase decreasing Na+ extrusion
the increase in intracellular Na+ content enhances Na+Ca2+ exchange so that as Na+ leaves the vells Ca2+ enters
= Ca2+ overload impairs myocardial contraction, possibly leading to cell death
What hastens recovery from ischemia during reperfusion?
inhibition of NHE or Na+Ca2+ exchange
What role does the NHE play against ischemic damage?
inhibition provides a protective role
in an MI, intracellular acidosis develops, and Na+ accumulates in myocytes
What is one of the most common causes of serious cardiac disease?
diminished coronary blood flow as a consequence of coronary artery disease
What is the impairment of myocardial contraction during MI produced by?
decrease in O2 delivery
metabolic substrates
accumulation of lactic acid, K+. H+ in cardiac tissues
What does a decrease in ATP concentration do during a MI cause?
Due to the rate of oxidative phosphorylation decreased
ATP concentration falls
ADP is formed further hydrolyzed to AMP and converted to adenosine
What does an MI cause in adenosine?
about 100-fold increase in interstitial adenosine and stimulates adenosine receptors
Where are A1 receptors located?
on the plasma membrane of cardiomyocytes
What is the action of A1 receptors when stimulated (SA and in the ventricle)?
antiadrenergic effect
in SA node = decrease in HR via same path as Ach
in ventricle = decrease rate of O2 consumption
What are intravenous injections of adenosine used to treat?
supraventricular tachycardia
stimulates A1 receptors on the AV node to rapidly decrease the ventricular rate
How do A1 receptors act on cardiac sensory nerve endings?
stimulation can result in chest pain
What does the rise of adenosine during ischemia link?
decrease of O2 delivery
oxidative phosphorylation
ATP content to chest pain
Where are the A2 receptors located?
on vascular smooth muscle of coronary arterioles
When stimulated what do A2 receptors cause?
vasodilation
What does intracoronary infusion of adenosine cause?
increase in coronary blood flow five-fold
What does the dramatic increase in adenosine formation cause during an MI?
increase in interstitial adenosine that stimulates A2 receptors, resulting in vasodilation
How does adenosine overall decrease the severity of ischemia?
by increasing coronary blood flow
decreasing MVO2 by decreasing HR and contractility
What is myocardial stunning?
a relatively brief period of every ischemia followed my reperfusion
maybe associated with mechanical dysfunction, can fully recover after a period of hours to days
How can myocardial stunning be prevented?
by preconditioning
involves one or more brief occlusions of a coronary artery
*prolonged occlusion in the absence of brief occlusions would impair the contractile force
How would long-term dipyridamole protect from ischemia-induced impairment of cardiac function?
preconditioning may involve adenosine release
dipyridamole blocks cellular uptake of attention = rise in blood levels of adenosine
A1 receptor antagonist would abolish the effect
When do collateral vessels develop?
if the narrowing of a coronary artery or branch occurs slowly and progressively
What is the function of collateral vessels?
supply sufficient blood to ischemic myocardium to prevent or decrease the extent of necrosis
How are collateral vessels developed?
originate from preexisting arterioles that undergo proliferative changes of endothelium and smooth muscle by arteriogenesis
What stimulates arteriogenesis?
shear stress is caused by enhanced blood flow velocity that occurs in arterioles proximal to occlusion
What is the process of arteriogenesis?
occlusion causes the pressure gradient along the proximal arterioles to increase because of greater perfusion pressure upstream
stress-activated endothelium upregulates expression of MCP-1 that attracts monocytes to invade arterioles (and other adhesion molecules and growth factors)
= remodelling and development of new enlarged collateral arteries
Are collateral arteries distinguishable from normal ones?
not after several months
What is capillary proliferation stimulated by?
VEGF
expression is upregulated by hypoxia
*mediated by adenosine release
Have any surgical attempts been able to enhance the development of collateral vessels?
no, they did not increase collateral circulation above that produced by coronary artery narrowing alone
