The coronary circulation receives 5% of the resting cardiac output from the left heart and mostly returns it to the right heart
The heart receives ~5% of the resting cardiac output, although it represents <0.5% of total body weight. The heart normally uses oxidative phosphorylation to generate the ATP required to pump blood. However, of all the O2 that the heart consumes, no more than 40% reflects the oxidation of carbohydrate. More than 60% of myocardial O2 consumption in the fasting state is due to the oxidation of fatty acids. The myocardium readily oxidizes ketone bodies (see p. 1185), which can provide considerable energy during starvation or during diabetic ketoacidosis. When the O2 supply is adequate, the heart takes up and oxidizes both lactate and pyruvate, as do red (i.e., oxidative) skeletal muscle fibers, although the arterial concentration of pyruvate is usually low. When the energetic demand for ATP exceeds the supply of O2, the heart can no longer take up lactate, but instead releases lactate by breaking down its own glycogen stores. In this manner, the heart can continue to function for a short time when it is deprived of O2. If hypoxia develops in the myocardium, nociceptive fibers trigger the sensation of referred pain, known as angina pectoris. More severe or prolonged insults damage the myocardial tissue, which eventually becomes necrotic—myocardial infarction.
The entire blood supply to the myocardium derives from the right and left coronary arteries, which originate at the root of the aorta behind the cusps of the aortic valves (Fig. 24-3). Although the anatomy is subject to individual variation, the right coronary artery generally supplies the right ventricle and atrium, and the left coronary artery supplies the left ventricle and atrium. The left coronary artery divides near its origin into two principal branches: The left circumflex artery sends branches to the left atrium and ventricle, and the left anterior descending artery descends to the apex of the heart and branches to supply the interventricular septum and a portion of the right as well as the left ventricle. These arteries course over the heart, branching into segments that penetrate into the tissue and dividing into capillary networks. Capillary density in histological sections of the human heart exceeds 3000 per square millimeter (skeletal muscle has only ~400 per square millimeter). The small diameter of cardiac muscle fibers (<20 µm), less than half that of skeletal muscle (~50 µm), facilitates O2 diffusion into the cardiac myocytes, which have a high energetic demand.
FIGURE 24-3 Heart and coronary circulation. AV, atrioventricular; SA, sinoatrial.
Once blood passes through the capillaries, it collects in venules, which drain outward from the myocardium to converge into the epicardial veins. These veins empty into the right atrium via the coronary sinus. Other vascular channels drain directly into the cardiac chambers. These include the thebesian veins, which drain capillary beds within the ventricular wall. Because the deoxygenated blood carried by the thebesian veins exits predominantly into the ventricles, this blood flow bypasses the pulmonary circulation. Numerous collateral vessels among branches of the arterial vessels and throughout the venous system act as anastomoses; these provide alternative routes for blood flow should a primary vessel become occluded.
Extravascular compression impairs coronary blood flow during systole
In other systemic vascular beds, blood flow roughly parallels the pressure profile in the aorta, rising in systole and falling in diastole (see Fig. 22-3). However, in the coronary circulation, flow is somewhat paradoxical: Although the heart is the source of its own perfusion pressure, myocardial contraction effectively compresses the heart's own vascular supply. Therefore, the profile of blood flow through the coronary arteries depends on both the perfusion pressure in the aorta (Fig. 24-4, top panel) and the extravascular compression resulting from the contracting ventricles, particularly the left ventricle.
FIGURE 24-4 Coronary blood flow cycle. Bands at the beginning of systole and diastole reflect isovolumetric contraction and relaxation, respectively.
Blood flow in the left coronary artery may actually reverse transiently in early systole (see Fig. 24-4, middle panel) because the force of the left ventricle's isovolumetric contraction compresses the left coronary vessels and the aortic pressure has not yet begun to rise (i.e., aortic valve is still closed). As aortic pressure increases later during systole, coronary blood flow increases, but never reaches peak values. However, early during diastole, when the relaxed ventricles no longer compress the left coronary vessels and aortic pressure is still high, left coronary flow rises rapidly to extremely high levels. All told, ~80% of total left coronary blood flow occurs during diastole.
In contrast, the profile of flow through the right coronary artery (see Fig. 24-4, lower panel) is very similar to the pressure profile of its feed vessel, the aorta. Here, systole contributes a greater proportion of the total flow, and systolic reversal does not occur. The reason for this difference is the lower wall tension developed by the right heart, which pumps against the low resistance of the pulmonary circulation and does not occlude the right coronary vessels during contraction.
The impact of systolic contraction on the perfusion of the left coronary vessels is highlighted by the effect of ventricular fibrillation (see Fig. 21-14I). At the onset of this lethal arrhythmia, left coronary perfusion transiently increases, reflecting the loss of mechanical compression of the vasculature.
Changes in heart rate, because they affect the duration of diastole more than that of systole, also affect coronary flow. During tachycardia, the fraction of the cardiac cycle spent in diastole decreases, minimizing the time available for maximal left coronary perfusion. If the heart is healthy, the coronary vessels can adequately dilate in response to the metabolic signals generated by increased cardiac work, which offsets the negative effects of the shorter diastole. On the other hand, a high heart rate can be dangerous when severe coronary artery disease restricts blood flow. N24-5
Adverse Effects of Tachycardia on Left Coronary Perfusion
Contributed by Steve Segal, Emile Boulpaep
As shown in Figure 24-4, most of the blood flow to the left coronary artery occurs during diastole. During bradycardia, a greater proportion of time is spent in diastole. Although this effect promotes left coronary blood flow, the total requirement for blood flow falls. During tachycardia, the diastolic interval shortens relatively more than the systolic interval. Thus, if we were to sum up all the diastolic intervals that occur over the course of a minute, we would see that less total time is available for left coronary perfusion during diastole—even though the metabolic requirements of the left ventricle are much higher during tachycardia.
Coronary blood flow not only varies in time during the cardiac cycle, it also varies with depth in the wall of the heart. Blood flows to cardiac myocytes through arteries that penetrate from the epicardium toward the endocardium. During systole, the intramuscular pressure is greatest near the endocardium and least near the epicardium. All things being equal, the perfusion of the endocardium would therefore be less than that of the epicardium. However, total blood flows to the endocardial and epicardial halves are approximately equal because the endocardium has a lower intrinsic vascular resistance, and thus a greater blood flow during diastole. When the diastolic pressure at the root of the aorta is pathologically low (e.g., with aortic regurgitation) or coronary arterial resistance is high (e.g., with coronary artery occlusion), endocardial blood flow falls below the epicardial flow. Thus, the inner wall of the left ventricle often experiences the greatest damage with atherosclerotic heart disease.
Myocardial blood flow parallels myocardial metabolism
A striking feature of the coronary circulation is the nearly linear correspondence between myocardial O2 consumption and myocardial blood flow. This relationship persists in isolated heart preparations, emphasizing that metabolic signals are the principal determinants of O2 delivery to the myocardium. In a resting individual, each 100 g of heart tissue receives 60 to 70 mL/min of blood flow. Normally, the heart extracts 70% to 80% of the O2 content of arterial blood (normally ~20 mL/dL blood), so that the venous O2 content is extremely low (~5 mL/dL). Therefore, the myocardium cannot respond to increased metabolic demands by extracting much more O2 than it already does when the individual is at rest. The heart can meet large increases in O2 demand only by increasing coronary blood flow, which can exceed 250 mL/min per 100 g with exercise.
Because blood pressure normally varies within fairly narrow limits, the only way to substantially increase blood flow through the coronary circulation during exercise is by vasodilation. The heart relies primarily on metabolic mechanisms to increase the caliber of its coronary vessels. Adenosine has received particular emphasis in this regard. An increased metabolic activity of the heart, an insufficient coronary blood flow, or a fall in myocardial results in adenosine release. Adenosine then diffuses to the VSMCs, activating purinergic receptors to induce vasodilation by lowering [Ca2+]i (see Table 20-8). Thus, inadequate perfusion to a region of the myocardium would elevate interstitial adenosine levels, causing vasodilation and restoration of flow to the affected region.
When cardiac work increases, contracting myocytes release K+, resulting in a transient rise in [K+]o that may contribute to the initial increase in coronary perfusion (see Table 20-9). However, it is unlikely that K+ mediates sustained elevations in blood flow. When the O2 demand of cardiac myocytes exceeds O2 supply, a rise in the and a fall in the may also lower coronary vascular resistance and thereby increase local O2 delivery.
Coronary blood flow is relatively stable between perfusion pressures of ~70 mm Hg and >150 mm Hg. Thus, like that of the brain, the blood flow to the heart exhibits autoregulation. In addition to the myogenic response, fluctuations in adenosine and contribute to coronary autoregulation.
Although sympathetic stimulation directly constricts coronary vessels, accompanying metabolic effects predominate, producing an overall vasodilation
Sympathetic nerves course throughout the heart, following the arterial supply. Stimulation of these nerves causes the heart to beat more frequently and more forcefully. β1 adrenoceptors on the cardiac myocytes mediate these chronotropic and inotropic responses. As discussed in the preceding section, the increased metabolic work of the myocardium leads to coronary vasodilation via metabolic pathways. However, during pharmacological inhibition of the β1 receptors, which prevents the increase in metabolism, sympathetic nerve stimulation causes a coronary vasoconstriction. This response is the direct effect of sympathetic nerve activity on α adrenoceptors on the VSMCs of the coronary resistance vessels. Thus, blocking of β1 receptors “unmasks” adrenergic vasoconstriction. However, under normal circumstances (i.e., no β blockade), the tendency of the metabolic pathways to vasodilate far overwhelms the tendency of the sympathetic pathways to vasoconstrict.
Activation of the vagus nerve has only a mild vasodilatory effect on the coronary resistance vessels. This muted response is not due to insensitivity of the resistance vessels to acetylcholine, which elicits a pronounced vasodilation when it is administered directly. Rather, the release of acetylcholine from the vagus nerve is restricted to the vicinity of the sinoatrial node. Thus, the vagus nerve has a much greater effect on heart rate than on coronary resistance.
Collateral vessel growth can provide blood flow to ischemic regions
When a coronary artery or one of its primary branches becomes abruptly occluded, ischemia can produce necrosis (i.e., a myocardial infarct) in the region deprived of blood flow. However, if a coronary artery narrows gradually over time, collateral blood vessels may develop and ameliorate the reduced delivery of O2 and nutrients to the compromised area, preventing or at least diminishing tissue damage. Collateral vessels originate from existing vessel branches that undergo remodeling with the proliferation of endothelial and smooth-muscle cells. Stimuli for collateral development include angiogenic molecules (see pp. 481–482) released from the ischemic tissue and changes in mechanical stress in the walls of vessels supplying the affected region.
Vasodilator drugs may compromise myocardial flow through “coronary steal”
A variety of drugs can promote vasodilation of the coronary arteries. These are typically prescribed for patients with angina pectoris, the chest pain associated with inadequate blood flow to the heart (see p. 564). If the buildup of atherosclerotic plaque—which underlies angina pectoris—occurs in the large epicardial arteries, the increased resistance lowers the pressure in the downstream microvessels. Under such conditions, the physician should be cautious in using pharmacological agents to dilate the coronary vessels: In an ischemic area of the myocardium downstream from a stenosis, metabolic stimuli may have already maximally dilated the arterioles. Administration of a vasodilator can then increase the diameter of blood vessels only in nonischemic vascular beds that are parallel to the ischemic ones, which thereby decreases the pressure at the branch point, upstream from the stenosis. The result is coronary steal. When vasodilator therapy relieves angina, the favorable result is more likely attributable to the vasodilation of the noncoronary systemic vessels, which reduces peripheral resistance, thereby reducing the afterload during systole and thus the work of the heart.