This document discusses the physiology of the coronary circulation. It covers topics like microvascular anatomy, determinants of coronary blood flow and myocardial oxygen consumption, coronary autoregulation, and control of coronary vascular resistance. The coronary circulation balances oxygen supply and demand in the heart. Coronary blood flow increases during diastole to perfuse the heart muscle. Myocardial oxygen consumption is determined by factors like heart rate, blood pressure, and contractility. The coronary system maintains blood flow over a range of pressures via autoregulation. Endothelial cells, nerves, metabolites, and physical forces regulate resistance in small coronary vessels.

1. PHYSIOLOGY OF CORONARY
CIRCULATION

2. TOPICS COVERED
Microvascular anatomy
Coronary blood flow
Determinants of myocardial oxygen consumption
Coronary autoregulation
Endothelium-Dependent Modulation of Coronary Tone

3. Neural Control of Coronary Conduit and Resistance Arteries
Paracrine Vasoactive Mediators
Determinants of Coronary Vascular Resistance
Function of the Coronary Microcirculation
Intraluminal Physical Forces Regulating Coronary Resistance

4. CORONARY CIRCULATION
• Heart is responsible for generating the arterial pressure that is required
to perfuse the systemic circulation.
• At the same time, has its own perfusion impeded during the systolic
portion of the cardiac cycle.
• Balance between oxygen supply and demand is a critical determinant of
the normal beat-to-beat function of the heart.

5. MICRO VASCULAR ANATOMY

6. CONTROL OF CORONARY BLOOD FLOW
• Systolic contraction increases tissue pressure, redistributes perfusion
from the subendocardial to the subepicardial layers of the heart, and
impedes coronary arterial inflow.
• Coronary venous outflow, which peaks during systole
• During diastole, coronary arterial inflow increases with a transmural
gradient that favors perfusion to the subendocardial vessels. At this
time, coronary venous outflow falls

10. DETERMINANTS OF MYOCARDIAL
OXYGEN CONSUMPTION
• Myocardial oxygen extraction is near-maximal at rest, averaging 60% to
80% of arterial oxygen content
• Ability to increase oxygen extraction as a means to increase oxygen
delivery is limited to circumstances associated with sympathetic
activation and acute subendocardial ischemia
• Coronary venous oxygen tension (PVo2) can only decrease from 25 mm
Hg to approximately 15 mm Hg.

11. • Increases in myocardial oxygen consumption are primarily met by
proportional increases in coronary flow and oxygen delivery.
• Oxygen delivery is directly determined by arterial oxygen content (Cao2).
• This is equal to the product of hemoglobin concentration and arterial
oxygen saturation plus a small amount of oxygen dissolved in plasma that is
directly related to arterial oxygen tension (Pao2).
• Anemia results in proportional reductions in oxygen delivery .
• Hypoxia, due to the nonlinear oxygen dissociation curve, results in relatively
small reductions in oxygen content until Pao2 falls to the steep portion of
the oxygen dissociation curve (below 50 mm Hg).

12. OD CURVE

13. THE MAJOR DETERMINANTS OF
MYOCARDIAL OXYGEN CONSUMPTION :
• Heart rate,
• Systolic pressure (or myocardial wall stress),
• Left ventricular (LV) contractility.
Twofold increase in any of these individual determinants of
oxygen consumption requires an approximately 50% increase in
coronary flow.

15. CORONARY AUTOREGULATION

17. • Resting coronary blood flow under normal hemodynamic conditions
averages 0.7 to 1.0 mL/min/g and can increase between four- and
fivefold during vasodilation.
• The ability to increase flow above resting values in response to
pharmacologic vasodilation is termed coronary flow reserve
• Flow in the maximally vasodilated heart is dependent on coronary
arterial pressure.

18. • Maximum perfusion and coronary flow reserve are reduced when the
diastolic time available for subendocardial perfusion is decreased
(tachycardia) or the compressive determinants of diastolic perfusion
(preload) are increased.
• Coronary reserve also is diminished by anything that increases resting
flow, including increases in the hemodynamic determinants of oxygen
consumption (systolic pressure, heart rate, and contractility) and
reductions in arterial oxygen supply (anemia and hypoxia).

19. • Sometimes subendocardial ischemia can even develop in normal
coronaries.
• Coronary flow can be auto regulated to mean coronary pressure as low
as 40 mmHg.
• The lower auto regulatory pressure limit increases during tachycardia
because of an increase in flow requirements, as well as a reduction in the
time available for perfusion

21. • Subendocardial flow occurs primarily in diastole and begins to decrease
below a mean coronary pressure of 40 mm Hg.
• Subepicardial flow occurs throughout the cardiac cycle and is
maintained until coronary pressure falls below 25 mm Hg.
• This difference arises from increased oxygen consumption in the
subendocardium, requiring a higher resting flow level, as well as the
more pronounced effects of systolic contraction on subendocardial
vasodilator reserve
• The transmural difference in the lower autoregulatory pressure limit
results in vulnerability of the subendocardium to ischemia in the
presence of a coronary stenosis.

22. ENDOTHELIUM-DEPENDENT
MODULATION OF CORONARY TONE
• The major endothelium-dependent biochemical pathways involved in
regulating coronary epicardial and resistance artery diameter :
• NO
• Endothelium Dependent Hyperpolarizing factor
• Prostacyclin
• Endothelin

25. NEURAL CONTROL OF CORONARY
CONDUIT AND
RESISTANCE ARTERIES
• Sympathetic and vagal nerves innervate coronary conduit arteries and
segments of the resistance vasculature.
• Neural stimulation affects tone through mechanisms that alter vascular
smooth muscle as well as by stimulating the release of NO from the
endothelium.

26. CHOLINERGIC INNERVATION
• Resistance arteries dilate to acetylcholine, resulting in increases in
coronary flow
• In conduit arteries, acetylcholine normally causes mild coronary
vasodilation.
• Net action of a direct muscarinic constriction of vascular smooth muscle
counterbalanced by an endothelium dependent vasodilation caused by
direct stimulation of NOS and an increased flow mediated dilation from
concomitant resistance vessel vasodilation

29. SYMPATHETIC INNERVATION
• Under basal conditions, there is no resting sympathetic tone in the heart.
• In conduit arteries, sympathetic stimulation leads to alpha 1 constriction as
well as beta mediated vasodilation. The net effect is to dilate epicardial
coronary arteries.
• NO-mediated vasodilation is impaired, alpha1 constriction predominates and
can dynamically increase stenosis severity in asymmetrical lesions where the
stenosis is compliant.

31. • The effects of sympathetic activation on myocardial perfusion and coronary
resistance vessel tone are complex and dependent on the net actions of
beta1-mediated increases in myocardial oxygen consumption (resulting from
increases in the determinants of myocardial oxygen consumption), direct
beta2-mediated coronary vasodilation, and alpha1-mediated coronary
constriction.

32. PARACRINE VASOACTIVE
MEDIATORS AND
CORONARY VASOSPASM
• Paracrine factors are released from epicardial artery thrombi after activation
of the thrombotic cascade initiated by plaque rupture.
• They can modulate epicardial tone in regions near eccentric ulcerated
plaques that are still responsive to stimuli that alter smooth muscle
relaxation and constriction, leading to dynamic changes.
• They have differential effects on downstream vessel vasomotion that are
dependent on vessel size (conduit arteries versus resistance arteries) as well
as on the presence of a functionally normal endothelium.

33. SEROTONIN
• Activated platelets
• Vasoconstriction
• By contrast, it dilates coronary arterioles and increases coronary flow
through the endothelium-dependent release of NO.
• Atherosclerosis or circumstances in which NO production is impaired.

34. THROMBOXANE A2
• Potent vasoconstrictor
• Product of endoperoxide metabolism and released during platelet
aggregation
• Conduit arteries as well as isolated coronary resistance vessels

35. ADENOSINE DIPHOSPHATE
• Platelet-derived vasodilator
• Coronary microvessels as well as conduit arteries.
• Mediated by NO and abolished by removing the endothelium.

36. DETERMINANTS OF CORONARY
VASCULAR RESISTANCE
• The resistance to coronary blood flow can be divided into three major
components
• Epicardial arteries (R1)
• Microcirculatory resistance arteries and arterioles (R2)
• Extravascular compressive resistance (R3).

40. FUNCTION OF THE CORONARY
MICROCIRCULATION
• Individual coronary resistance arteries are a longitudinally distributed
network
• .
• Each resistance vessel needs to dilate in an orchestrated fashion to meet
the needs of the downstream vascular bed.
• Under resting conditions, most of the pressure drop in the
microcirculation arises in resistance arteries between 50 and 200 μm,
with little pressure drop occurring across capillaries and venules at
normal flow levels .

41. • Heterogeneity in microcirculatory vasodilation is evident during
physiologic adjustments in flow.
• As pressure is reduced during auto-regulation, dilation is accomplished
primarily by arterioles smaller than 100 μm, whereas larger resistance
arteries tend to constrict because of the reduction in perfusion pressure.
• By contrast, metabolic vasodilation results from a more uniform
vasodilation of resistance vessels of all sizes.
• A unique component of subendocardial coronary resistance vessels is
the transmural penetrating arteries.

42. INTRALUMINAL PHYSICAL FORCES
REGULATING CORONARY RESISTANCE
• Myogenic Regulation:
• Flow-Mediated Resistance Artery Control
• Metabolic Mediators of Coronary Resistance Vessel Control
1. Adenosine
2. ATP Sensitive K+ Channels
3. Oxygen Sensing
4. Acidosis

43. MYOGENIC REGULATION:
• Myogenic response refers to the ability of vascular smooth muscle to oppose
changes in coronary arterial diameter.
• Myogenic tone is a property of vascular smooth muscle and occurs across a
large size range of coronary resistance arteries.
• appears to primarily occur in arterioles smaller than 100 μm.

44. FLOW-MEDIATED RESISTANCE ARTERY
CONTROL
• Coronary small arteries and arterioles also regulate their diameter in response
to changes in local shear stress.
• Flow-induced dilation in isolated coronary arterioles is endothelium-dependent
and mediated by NO.
• EDHF may represent a compensatory pathway that normally is inhibited by NO
and becomes upregulated in acquired disease states in which NO-mediated
vasodilation is impaired.

45. METABOLIC MEDIATORS OF CORONARY
RESISTANCE VESSEL CONTROL
• Coronary resistance in any segment of the microcirculation represents
the integration of local physical factors (e.g., pressure and flow),
vasodilator metabolites (e.g., adenosine, Po2, and pH), autacoids, and
neural modulation.
• The net coronary vascular smooth muscle tone, which may ultimately be
controlled by opening and closing vascular smooth muscle adenosine
triphosphate (ATP)-sensitive K+ (KATP) channels

46. ADENOSINE
• It is released from cardiac myocytes when the rate of ATP hydrolysis exceeds
its synthesis during ischemia.
• Its production and release also increase with myocardial metabolism.
• adenosine deaminase
• Adenosine has a differential effect on coronary resistance arteries, primarily
dilating vessels smaller than 100 μm.

47. ATP SENSITIVE K+ CHANNELS
• Coronary vascular smooth muscle KATPchannels are tonically active,
contributing to coronary vascular tone under resting conditions.
• The KATP channels can modulate both the coronary metabolic and
autoregulatory responses. It is a potentially attractive mechanism, because
many of the other candidates for metabolic flow regulation (e.g., adenosine,
NO, beta2-adrenoreceptors, prostacyclin) are ultimately affected by blocking
this pathway.

48. OXYGEN SENSING
• Coronary flow increases in proportion to reductions in arterial oxygen
content (reduced Po2or anemia) and there is a two-fold increase in
perfused capillary density in response to hypoxia. The underlying
mechanism may involve the release of NO and ATP (which stimulates
vascular endothelial P2 receptors to produce NO) from red blood cells,
when intravascular Po2levels drop

49. ACIDOSIS
• Arterial hypercapnia and acidosis (P) are potent stimuli that have been
demonstrated to produce coronary vasodilation independent of hypoxia.
• Their precise role in the local regulation of myocardial perfusion remains
unclear