Coronary Blood Flow

Coronary Blood Flow:
The heart is an aerobic organ that is dependent for its oxygen supply entirely on coronary perfusion. Under resting condition, the myocardium extracts the maximum amount of oxygen from the blood it receives. The O2 saturation of blood returning from the coronary sinus to the right atrium has the lowest saturation of any body organ (30%). Interruption of coronary blood flow will result in immediate ischemia. Coronary blood flow is directly dependent upon perfusion pressure and inversely proportional to the resistance of the coronary vessel.

Q ∞ Perfusion pressure / Vessel resistance

Coronary perfusion occurs in diastole hence diastolic pressure is more important than systolic pressure in determining coronary perfusion. Coronary vessels are divided into epicardial or conductance vessels (R1), pre capillary (R2) and microvascular vessels (R3). The epicardial vessels, the site most commonly affected by atherosclerosis, offer negligible resistance to coronary flow. Resistance to flow occurs in the pre capillary (R2), and microvascular (R3) vessels which are termed resistance vessels. The increase coronary blood flow in response to increase myocardial oxygen demand (MVO2) is achieved by the dilatation of these resistance vessels. Three factors play a key role in modifying vascular tone; the accumulation of local metabolites, endothelial factors and neural tone. The accumulation of adenosine during ischemia is an example of local metabolic factors. The most important endothelial substance mediating vasodilatation is nitric oxide (NO). Other important mediators are bradykinin, endothelium derived hyperpolarizing factor and prostacyclin. On the other hand, endothelin-1 (ET-1) is a well known vasoconstricting substance. Angiotensin II and thromboxane A2 are other well known endothelium derived constricting factors. Alpha receptor adrenergic stimulation results in coronary vasoconstriction whereas beta 1 receptor stimulation leads to vasodilatation. Coronary vascular resistance can be reduced to 1/5th of baseline resistance leading to a five fold increase in the volume of perfusion in response to an increase in need. Coronary reserve is the term used to reflect the amount of increase in coronary perfusion to accommodate increased demand. Autoregulation, mediated by changes in the vascular tone of the resistance vessels, allows distal coronary perfusion to remain unaltered in the face of changes in proximal perfusion pressures. Impaired endothelial function disrupts autoregulation and may lead to ischemia. Diseases known to impair endothelial function include atherosclerosis, dyslipidemias, diabetes mellitus, hypertension, smoking (both passive and active) and hyperhomocysteinemia. Coronary arteries suffering from atherosclerosis lose the ability to release the vasodilating substances that allow the increase in coronary perfusion in the face of increased demand. Their coronary reserve is limited by the failure to dilate and reduce vascular resistance. Furchgott showed that acetylcholine, through the release of NO, results in vasodilation of the coronary vessel. However if the endothelium overlying the vascular smooth vessel was diseased (e.g. by atherosclerosis), the smooth muscle will paradoxically vasoconstrict.

Blockage of the epicardial coronary vessels (coronary stenosis) of up to 60% is compensated at rest and maximal exercise by vasodilation of the resistance coronary vessels. Blockage of epicardial coronary vessels in excess of 60% will result, under conditions of increases myocardial oxygen demand, in reduced perfusion and in turn ischemia. Clinically, this translates to effort or exercise induced angina. This is the basis for performing exercise stress testing in patients suspected of having coronary artery disease. When the severity of the blockage is greater than 90%, perfusion is compromised even at rest. Clinically, this may result in resting angina, a critical stage of coronary artery disease. Ischemia is the result of the coronary vessel’s inability to meet the demand of the myocardium it supplies. The imbalance between supply and demand (↑ demand, ↓ supply) results in ischemia. Clinically this presents as chest discomfort and / or shortness of breath.

The Determinants of Myocardial O2 Consumption:
The major determinants of myocardial O2 consumption (MVO2) are 1) heart rate 2) ventricular wall stress (afterload) and 3) contractility (inotropy). Heart rate is the main determinant of MVO2. Ventricular wall stress, as defined by Laplace’s law, is the product of the left ventricular systolic pressure and the radius of the left ventricle divided by its wall thickness. Hence, processes such as aortic stenosis and hypertension, which increase systolic pressure, mitral and aortic regurgitation, which increase LV cavity size, increase myocardial oxygen consumption. During exercise stress testing MVO2 can be described using the “double product,” the product of the maximal systolic pressure and heart rate attained during maximal exercise. This formula represents the two key components of myocardial oxygen demand.