Myocardial Oxygen Supply

• The oxygen requirements of the myocardium are continuously matched by the coronary arterial supply.

Myocardial Oxygen Supply

• Oxygen supply to the myocardium depends on the oxygen content of the blood and the rate of coronary blood flow.
• Coronary blood flow is much more dynamic, and regulation of that flow is responsible for matching the oxygen supply with metabolic requirements.
• Coronary artery flow (Q) is directly proportional to the vessel's perfusion pressure (P) and is inversely proportional to the coronary vascular resistance (R): Q α P/R.
• Predominance of coronary perfusion from the aorta occurs during diastole, not systole.
• Systolic flow is impaired by the compression of small coronary branches as they course through contracting myocardium.
• Perfusion pressure can be approximated by the aortic diastolic pressure (or more accurately, by the difference between the aortic diastolic pressure and the left ventricular diastolic pressure).
• Lower aortic diastolic pressure (such as hypotension or aortic valve regurgitation) reduces coronary artery perfusion pressure, which may decrease myocardial oxygen supply.
• Coronary vascular resistance is the other major determinant of coronary blood flow
• Resistance is dynamically modulated by forces that externally compress the coronary arteries and factors that alter intrinsic coronary tone.
• External compression is exerted on the coronary vessels during the cardiac cycle by contraction of the surrounding myocardium.
• The subendocardium is the region most vulnerable to ischemic damage because it increases the intraventricular pressure.
• The heart cannot increase oxygen extraction on demand because, in its basal state, it removes nearly as much oxygen as possible from its blood supply
• any additional oxygen requirement must be met by an increase in blood flow
• Autoregulation of coronary vascular resistance is the most important mediator of this process.
• Factors participating in regulation of coronary vascular resistance include the accumulation of local metabolites, endothelium-derived substances, and neural innervation.
• The accumulation of local metabolites significantly affects coronary vascular tone, modulating myocardial oxygen supply to meet changing metabolic demands.
• During states of tissue hypoxia, aerobic metabolism and oxidative phosphorylation in the mitochondria are inhibited, which impairs ATP generation.
• Adenosine diphosphate (ADP) and adenosine monophosphate (AMP) accumulate and are degraded to adenosine.
• Adenosine causes the relaxation, vasodilatation, and increased coronary blood flow.
• Other metabolites act locally as vasodilators, include lactate, acetate, hydrogen ions, and carbon dioxide.
• Endothelial cells of arterial wall produce vasoactive substances that contribute to the regulation of vascular tone
• Vasodilators produced by the endothelium include nitric oxide (NO), prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). Endothelin 1 is an example of an endothelium-derived vasoconstrictor.
• NO regulates vascular tone by diffusing into and relaxing neighboring arterial smooth muscle by a cyclic guanosine monophosphate (cGMP)-dependent mechanism.
• Its release is augmented when the endothelium is exposed to acetylcholine (ACh), thrombin, products of aggregating platelets (eg, serotonin and ADP), or even the shear stress of blood flow.
• Endothelial-derived NO hyperpolarizes neighboring vascular smooth muscle cells.
• Endothelin 1 partially counteracts actions of the endothelial vasodilators.
• Its expression is stimulated by several factors, including thrombin, angiotensin II, epinephrine, and the shear stress of blood flow.
• Neural control of vascular resistance includes sympathetic and parasympathetic components
• Coronary vessels contain α-adrenergic and β₂-adrenergic receptors; stimulation of α-adrenergic receptors= vasoconstriction; stimulation of β₂-receptors=vasodilation.
• Interaction among metabolic, endothelial, and neural regulating factors determines net impact on coronary vascular tone.