Coronary Blood flow and Cardiac Work

Coronary artery vasodilation

Adenosine is the most important regulator of coronary blood flow, and is a metabolite of cardiac muscle work The greater the cardiac work, the more adenosine produced the greater the vasodilation Other vasodilators include NO, Ach, PGL2 and shear stress

Collateralization of coronary blood vessels

Anastomotic channels, connections between coronary arteries, are known as collateral vessels Collateral vessels can develop as an adaptation to ischemia They can serve as conduits that bridge stenoses or provide a dual connection to a region of the heart (an alternative source of blood supply to myocardium) Collaterals can be life saving if occlusive coronary artery disease is present Two classes of collateral vessels have been recognized: capillary sized and larger epicardial collaterals

Specific Autoregulation of CBF

Myocardial autoregulation is preserved from the resting to exercise state Autoregulation is present over the "physiological range" of coronary perfusion pressures *Illustration of autoregulation in coronary vasculature and the effect of metabolic activity on the position of the autoregulatory region. When cardiac metabolism increases, as during exercise, autoregulation persists as the pressure-flow relation shifts upward. Concept: coronary blood flow is autoregulated ---this is all that needs to be learned from this graphical representation of the myocardial flow property---no need to learn specific numbers.

Coronary blood flow parallels myocardial oxygen consumption

Myocardial oxygen consumption per minute is abbreviated mVO2 and since the efficient pathways of oxidative metabolism allow the heart to meet its demand for ATP by oxidizing fat, carbohydrates, and some protein, all by oxidative phosphorylation, and since energy production equals energy consumption, the utilization of energy by the heart is estimated by mVO2 The "dot" over the V means "per minute" and this convention will be used in respiratory data also (may not always put in the dot) Estimates of mVO2 include: a) the contractile state of the myocardium; b) external P-V work (P-V loop area; aortic pressure x CO); c) (the double product) aortic pressure x HR (chronoropic state); d) average ejection pressure x duration of ejection (the tension-time index); and e) lusitropic (relaxation) properties of the myocardium.

Sympathetic stimulation vs. metabolic effects on CBF

Nevertheless, there is autonomic control of CBF, specifically sympathetic vasoconstriction β1 Sympathoexcitation to the heart increases HR and force of contraction which increase metabolism which secondarily increase CBF Underlying the β1 adrenergic effect there is an α adrenergic vasoconstriction but it is much less than the metabolic vasodilation Parasympathetic vasodilation of coronary vessels is present but the release of te neurotransmitter Ach is mostly limited to the region of the SA node; hence, parasympathetic activation to the heart is mostly chronotropic. Injection of Ach causes greater vasodilation but this is a synergistic interaction with NO

Comparative circulation controls

Note the most important mechanism in coronary, cerebral, pulmonary and renal circulations is local metabolic control

Physical effects on cbf

Perfusion pressure of the coronary arteries must overcome the myocardial compression during systole Extravascular compression impairs coronary blood flow during systole The heart is its own source of perfusion pressure but effectively compresses its own vascular supply Pericardium also can have a compressive effect on the coronary vessels (pericardial tamponade, pathophysiology) LV hypertrophy is an adaptation to chronically pumping against greater volume load or afterload and the increased bulk of tissue can impair coronary blood flow

Adenosine production and mechanism of action

The metabolic path for adenosine production and degradation together with the cellular targets of adenosine. ADP, adenosine diphosphate; ATP, adenosine triphosphate; A-V atrio-ventricular, cAMP, cyclic adenosine monophosphate; Gi, guanine nucleotide inhibitory protein; HR, heart rate; MVO2, maximal rate of O2 consumption; SA, sinoatrial; ↓, decrease in.

Myocardial Oxygen supply is balanced with cbf

The metabolic rate of the myocardium ( rest, exercise, disease) will be related to the amount of metabolites produced. These metabolic products have vasodilation effects on vascular smooth muscle and the coronary arteries are especially susceptible to metabolic vasodilation.

left and right CBF during systole and diastole

Transmural pressure (Pinside - Poutside) of coronary arteries decreases during systole Notice the flows during isovolumic contraction and relaxation Highest coronary flow in LV is during diastole What happens to LV flow with high heart rates?

stable angina pectoris

Angina is the symptom of pain in upper left quadrant as a result of coronary ischemia Ischemia is evident here from increased lactate production (lactate level in coronary sinus) With increased demand on ischemic heart, the cardiac preload increases, why is that? Coronary ischemia is evidenced by ST segment depression in the ECG *Concept: insufficient CBF to meet the metabolic requirements of the heart as a symptom of pain, a sign of ST segment depression and evidence of increased lactate production in the coronary venous flow.

Neural: acetylcholine effect on cbf

Both the vasodilation from Ach neurotransmitter release and direct Ach injection are related to the Ach-induced release of NO from endothelial cells *Concept: parasympathetic and direct Ach injection effects on coronary blood flow are mostly the result of Ach causing release of NO, a powerful vasodilator of vascular smooth muscle

Summary: coronary blood flow control

+ = increase in coronary vascular R (vasoconstriction) - = decrease in coronary vascular R (vasodilation) Metabolic plus myogenic mechanisms contribute to autoregulation of CBF

Clinical relevance of cbf

1. Collateral vessel growth as adaptation to increased metabolic needs 2. Coronary steal phenomenon 3. Atherosclerosis of coronary arteries 4. Angioplasty and stents 5. Coronary reserve capacity 6. Angina pectoris and myocardial ischemia

Autoregulation of organ blood flow

Autoregulation is the tendency toward constancy of blood flow in an organ with increases or decreases in its driving pressure Individual organ systems have different degrees of autoregulation The myocardium is highly autoregulated and this is related to its flow being mostly controlled by local metabolic factors (review hemodynamic presentation) *This is a general diagram showing the principle of autoregulation; the myocardium, brain and kidney systems Concepts to grasp: myocardium is autoregulated; there is a physiological range over which autoregulation occurs; metabolites are involved in autoregulation

Review: Primary influences on systemic arteries and veins

Coronary arteries are not primarily under autonomic control, but rather are predominately controlled by vasodilator metabolites

Coronary reserve

Coronary flow reserve (CFR) is the maximum increase in blood flow that can occur through the coronary arteries above the normal resting flow. Its measurement is often used in medicine to assist in the treatment of conditions affecting the coronary arteries and to determine the efficacy of treatments used.

Coronary steal phenomenon

Coronary steal (with its symptoms termed cardiac steal syndrome) is where an alteration of circulation patterns lead to a reduction in the blood directed to the coronary circulation. It is caused when there is narrowing of coronary arteries and a coronary vasodilator is used - "stealing" blood away from those parts of the heart. Dilating resistance vessels in the coronary circulation causes blood to be shunted away from the coronary vessels supplying the ischemic zones, creating more ischemia Dipyridamole is a coronary vasodilator drug

Summary

Functional anatomy of the coronary vessels (review) Extravascular compression affects coronary blood flow Coronary blood flow parallels myocardial oxygen consumption Sympathetic stimulation vs. metabolic effects on CBF Clinical applications: collateral vessel growth, coronary steal phenomenon, atherosclerosis and coronary artery disease, angioplasty and stents

Extravascular compression affects coronary blood flow

The transmural pressure that coronary arteries experience after they have dived into the myocardium, is again equal to the (greater) inside pressure minus the (lesser) outside pressure The other arteries that experience compression are those within skeletal muscles, but with skeletal muscle such compressions are beneficial in aiding venous flow

Coronary atherosclerosis

a. Before angioplasty b. After angioplasty