L44 Regulation of Coronary Blood Flow PDF

44 Regulation of coronary blood flow By the end of this lecture, students will be able to: Describe the coronary blood flow and its phasic changes in relation to the cardiac cycle Interpret the relative importance of local, metabolic, and neural control of coronary blood flow VARIATIONS IN CORONARY...

44 Regulation of coronary blood flow By the end of this lecture, students will be able to: Describe the coronary blood flow and its phasic changes in relation to the cardiac cycle Interpret the relative importance of local, metabolic, and neural control of coronary blood flow VARIATIONS IN CORONARY FLOW At rest the myocardium receives about 5% of cardiac output (225-250 ml/min). During exercise there is about fivefold increase in cardiac output which is mainly provided by increased coronary blood flow. At rest, the heart extracts 70–80% of the O2 from each unit of blood delivered to it. O2 consumption can be increased significantly only by increasing blood flow. Therefore, it is not surprising that blood flow increases when the metabolism of the myocardium is increased. PHASIC CHANGES IN CORONARY BLOOD FLOW The heart is a muscle that, like skeletal muscle, compresses its blood vessels when it contracts. The pressure inside the left ventricle is slightly higher than in the aorta during systole. Consequently, flow occurs in the arteries supplying the subendocardial portion of the left ventricle only during diastole, although the force is sufficiently dissipated in the more superficial portions of the left ventricular myocardium to permit some flow in this region throughout the cardiac cycle. Therefore, the subendocardial layers of the heart muscle are more prone to ischaemic damage and are the most common site of myocardial infarction, especially in the left ventricle. Because diastole is shorter when the heart rate is high, left ventricular coronary flow is reduced during pathological tachycardia, however, in sinus (physiological tachycardia) as during muscular exercise, this effect is overridden by metabolic autoregulation. (Fig.1) Fig.1: Phasic changes of coronary blood flow AUTOREGULATION OF CORONARY BLOOD FLOW The diameter of the coronary vessels, and consequently the rate of coronary blood flow, is influenced by autoregulation, pressure changes in the aorta and neural factors. Autoregulation means the ability of the myocardium to maintain stable blood flow despite variations in coronary pressure. This is explained by the myogenic and metabolic mechanisms. Myocardial oxygen demand coupled to the production of vasodilator metabolites is the primary controller of the coronary blood flow. CHEMICAL FACTORS Factors may induce vasodilatation include O2 lack and increased local concentrations of CO2, H+, K+, lactate, prostaglandins, adenine nucleotides, and adenosine. A major part of this vasodilator action is mediated by the opening of ATP-sensitive K+ channels. This leads to hyperpolarization and consequently relaxation of the smooth muscle. Hypoxia can increase coronary blood flow 200– 300%, A similar increase in flow is produced in the area supplied by a coronary artery if the artery is occluded and then released (reactive hyperemia) which may be due to release of adenosine. (Fig.2) NEURAL FACTORS The coronary arterioles contain α-adrenergic receptors, which mediate vasoconstriction, and β-adrenergic receptors, which mediate vasodilation. Activity in the noradrenergic nerves to the heart and injections of norepinephrine cause coronary vasodilation. However, norepinephrine increases the heart rate and the force of cardiac contraction, and the vasodilation is due to production of vasodilator metabolites in the myocardium secondary to the increase in its activity. When the inotropic and chronotropic effects of noradrenergic discharge are blocked by a βadrenergic blocking drug, stimulation of the noradrenergic nerves or injection of norepinephrine in animals elicits coronary vasoconstriction. Thus, the direct effect of noradrenergic stimulation is constriction rather than dilation of the coronary vessels. When the systemic blood pressure falls, the overall effect of the reflex increase in noradrenergic discharge is increased coronary blood flow secondary to the metabolic changes in the myocardium at a time when the cutaneous, renal, and splanchnic vessels are constricted. In this way the circulation of the heart, like that of the brain, is preserved when flow to other organs is compromised. On the other hand, stimulation of vagal fibres to the heart mildly dilates the coronaries by a direct effect mediated by release of nitic oxide. However, vagal stimulation has a negative inotropic and chronotropic effect which decreases cardiac metabolism resulting in more powerful indirect coronary vasoconstriction. Fig.2: Autoregulation of coronary blood flow