Muscle Blood Flow and Cardiac Output During Exercise; the Coronary Circulation and Ischemic Heart Disease In this chapter we consider (1) blood flow to the skeletal muscles and (2) coronary artery blood flow to the heart. Regulation of each of these types of blood flow is achieved mainly by local control of vascular resistance in response to muscle tissue metabolic needs. We also discuss the physiology of related subjects such as (1) cardiac output control during exercise, (2) characteristics of heart attacks, and (3) the pain of angina pectoris. BLOOD FLOW REGULATION IN SKELETAL MUSCLE AT REST AND DURING EXERCISE Strenuous exercise is one of the most stressful conditions that the normal circulatory system faces because there is such a large mass of skeletal muscle in the body, all of it requiring large amounts of blood flow. Also, the cardiac output often must increase to four to five times normal in the nonathlete, or to six to seven times normal in the well-trained athlete, to satisfy the metabolic needs of the exercising muscles. RATE OF BLOOD FLOW THROUGH THE MUSCLES During rest, blood flow through skeletal muscle averages 3 to 4 ml/min/100 g of muscle. During extreme exercise in the well-conditioned athlete, this blood flow can increase 25- to 50-fold, rising to 100 to 200 ml/min/100 g of muscle. Peak blood flows as high as 400 ml/min/100 g of muscle have been reported in thigh muscles of endurance-trained athletes. Blood Flow During Muscle Contractions. Figure 21-1 shows a record of blood flow changes in a calf muscle of a human leg during strong rhythmical muscular exercise. Note that the flow increases and decreases with each muscle contraction. At the end of the contractions, the blood flow remains very high for a few seconds but then returns toward normal during the next few minutes. The cause of the lower flow during the muscle contraction phase of exercise is compression of the blood vessels by the contracted muscle. During strong tetanic contraction, which causes sustained compression of the blood vessels, the blood flow can be almost stopped, but this also causes rapid weakening of the contraction. Increased Blood Flow in Muscle Capillaries During Exercise. During rest, some muscle capillaries have little or no flowing blood, but during strenuous exercise, all the capillaries open. This opening of dormant capillaries diminishes the distance that oxygen and other nutrients must diffuse from the capillaries to the contracting muscle fibers and sometimes contributes a twofold to threefold increased capillary surface area through which oxygen and nutrients can diffuse from the blood to the tissues. CONTROL OF BLOOD FLOW IN SKELETAL MUSCLES Decreased Oxygen in Muscle Greatly Enhances Flow. The tremendous increase in muscle blood flow that occurs during skeletal muscle activity is caused mainly by chemicals acting directly on the muscle arterioles to cause dilation. One of the most important chemical effects is reduction of oxygen in the muscle tissues. When muscles are active they use oxygen rapidly, thereby decreasing the oxygen concentration in the tissue fluids. This in turn causes local arteriolar vasodilation because the arteriolar walls cannot maintain contraction in the absence of oxygen and because oxygen deficiency causes release of vasodilator substances. Adenosine may be an important vasodilator substance, but experiments have shown that even large amounts of adenosine infused directly into a muscle artery cannot increase blood flow to the same extent as during intense exercise and cannot sustain vasodilation in skeletal muscle for more than about 2 hours. Fortunately, even after the muscle blood vessels have become insensitive to the vasodilator effects of adenosine, still other vasodilator factors continue to maintain increased capillary blood flow as long as the exercise continues. These factors include (1) potassium ions, (2) adenosine triphosphate (ATP), (3) lactic acid, and (4) carbon dioxide. We still do not know quantitatively how great a role each of these factors plays in increasing 259 Unit IV The Circulation Blood flow (¥100 ml/min) 40 Rhythmic exercise 20 Calf flow0 010 1618 Minutes Figure 21-1. Effects of muscle exercise on blood flow in the calf of a leg during strong rhythmical contraction. The blood flow was much less during contractions than between contractions. (Modified from Barcroft H, Dornhorst AC: The blood flow through the human calf during rhythmic exercise. J Physiol 109:402, 1949.) muscle blood flow during muscle activity; this subject was discussed in additional detail in Chapter 17. Nervous Control of Muscle Blood Flow. In addition to local tissue vasodilator mechanisms, skeletal muscles are provided with sympathetic vasoconstrictor nerves and (in some species of animals) sympathetic vasodilator nerves as well. Sympathetic Vasoconstrictor Nerves. The sympathetic vasoconstrictor nerve fibers secrete norepinephrine at their nerve endings. When maximally activated, this mechanism can decrease blood flow through resting muscles to as little as one-half to one-third normal. This vasoconstriction is of physiologic importance in attenuating decreases of arterial pressure in circulatory shock and during other periods of stress when it may even be necessary to increase blood pressure. In addition to the norepinephrine secreted at the sympathetic vasoconstrictor nerve endings, the medullae of the two adrenal glands also secrete large amounts of norepinephrine plus even more epinephrine into the circulating blood during strenuous exercise. The circulating norepinephrine acts on the muscle vessels to cause a vasoconstrictor effect similar to that caused by direct sympathetic nerve stimulation. The epinephrine, however, often has a slight vasodilator effect because epinephrine excites more of the beta-adrenergic receptors of the vessels, which are vasodilator receptors, in contrast to the alpha vasoconstrictor receptors excited especially by norepinephrine. These receptors are discussed in Chapter 61. CIRCULATORY READJUSTMENTS DURING EXERCISE Three major effects occur during exercise that are essential for the circulatory system to supply the tremendous blood flow required by the muscles. They are (1) sympathetic nervous system activation in many tissues with consequent stimulatory effects on the circulation, (2) increase in arterial pressure, and (3) increase in cardiac output. Effects of Sympathetic Activation At the onset of exercise, signals are transmitted not only from the brain to the muscles to cause muscle contraction but also into the vasomotor center to initiate sympathetic discharge in many other tissues. Simultaneously, the parasympathetic signals to the heart are attenuated. Therefore, three major circulatory effects result. First, the heart is stimulated to a greatly increased heart rate and increased pumping strength as a result of the sympathetic drive to the heart plus release of the heart from normal parasympathetic inhibition. Second, most of the arterioles of the peripheral circulation are strongly contracted, except for the arterioles in the active muscles, which are strongly vasodilated by the local vasodilator effects in the muscles, as noted earlier. Thus, the heart is stimulated to supply the increased blood flow required by the muscles, while at the same time blood flow through most nonmuscular areas of the body is temporarily reduced, thereby “lending” blood supply to the muscles. This process accounts for as much as 2 L/min of extra blood flow to the muscles, which is exceedingly important when one thinks of a person running for his or her life, when even a fractional increase in running speed may make the difference between life and death. Two of the peripheral circulatory systems, the coronary and cerebral systems, are spared this vasoconstrictor effect because both these circulatory areas have poor vasoconstrictor innervation—fortunately so, because both the heart and the brain are as essential to exercise as are the skeletal muscles. Third, the muscle walls of the veins and other capacitative areas of the circulation are contracted powerfully, which greatly increases the mean systemic filling pressure. As we learned in Chapter 20, this effect is one of the most important factors in promoting increase in venous return of blood to the heart and, therefore, in increasing the cardiac output. Sympathetic Stimulation May Increase Arterial Pressure During Exercise An important effect of increased sympathetic stimulation in exercise is to increase the arterial pressure. This increased arterial pressure results from multiple stimulatory effects, including (1) vasoconstriction of the arterioles and small arteries in most tissues of the body except the brain and the active muscles, including the heart, (2) increased pumping activity by the heart, and (3) a great increase in mean systemic filling pressure caused mainly by venous contraction. These effects, working together, almost always increase the arterial pressure during exercise. This increase can be as little as 20 mm Hg or as great as 80 mm Hg, depending on the conditions under which the exercise is performed. When a person performs 260 Chapter 21 Muscle Blood Flow and Cardiac Output During Exercise exercise under tense conditions but uses only a few muscles, the sympathetic nervous response still occurs. In the few active muscles, vasodilation occurs, but elsewhere in the body the effect is mainly vasoconstriction, often increasing the mean arterial pressure to as high as 170 mm Hg. Such a condition might occur in a person standing on a ladder and nailing with a hammer on the ceiling above. The tenseness of the situation is obvious. Conversely, when a person performs massive wholebody exercise, such as running or swimming, the increase in arterial pressure is often only 20 to 40 mm Hg. This lack of a large increase in pressure results from the extreme vasodilation that occurs simultaneously in large masses of active muscle. Why Is Increased Arterial Pressure During Exercise Important? When muscles are stimulated maximally in a laboratory experiment but without allowing the arterial pressure to rise, muscle blood flow seldom rises more than about eightfold. Yet, we know from studies of marathon runners that muscle blood flow can increase from as little as 1 L/min for the whole body during rest to more than 20 L/min during maximal activity. Therefore, it is clear that muscle blood flow can increase much more than occurs in the aforementioned simple laboratory experiment. What is the difference? Mainly, the arterial pressure rises during normal exercise. Let us assume, for instance, that the arterial pressure rises 30 percent, a common increase during heavy exercise. This 30 percent increase causes 30 percent more force to push blood through the muscle tissue vessels. However, this is not the only important effect; the extra pressure also stretches the walls of the vessels, and this effect, along with the locally released vasodilators and higher blood pressure, may increase muscle total flow to more than 20 times normal. Importance of the Increase in Cardiac Output During Exercise Many different physiologic effects occur at the same time during exercise to increase cardiac output approximately in proportion to the degree of exercise. In fact, the ability of the circulatory system to provide increased cardiac output for delivery of oxygen and other nutrients to the muscles during exercise is equally as important as the strength of the muscles themselves in setting the limit for continued muscle work. For instance, marathon runners who can increase their cardiac outputs the most are generally the ones who have record-breaking running times. Graphical Analysis of the Changes in Cardiac Output During Heavy Exercise. Figure 21-2 shows a graphical analysis of the large increase in cardiac output that occurs during heavy exercise. The cardiac output and venous return curves crossing at point A give the analysis for the normal circulation, and the curves crossing at point B analyze heavy exercise. Note that the great increase in cardiac output requires significant changes in both the 25 B Cardiac output and venous return (L/min) 20 15 TINUIV 10 A5 0 40+4+8+12+16+20+24 Right atrial pressure (mm Hg) Figure 21-2. Graphical analysis of change in cardiac output, venous return, and right atrial pressure with onset of strenuous exercise. Black curves, normal circulation. Red curves, heavy exercise. cardiac output curve and the venous return curve, as follows. The increased level of the cardiac output curve is easy to understand. It results almost entirely from sympathetic stimulation of the heart that causes (1) increased heart rate, often up to rates as high as 170 to 190 beats/min, and (2) increased strength of contraction of the heart, often to as much.implifyexplainsummarieithoutmissing

Muscle Blood Flow and Cardiac Output During Exercise; the Coronary Circulation and Ischemic Heart Disease In this chapter we consider (1) blood flow to the skeletal muscles and (2) coronary artery blood flow to the heart. Regulation of each of these types of blood flow is achieved mainly by local control of vascular resistance in response to muscle tissue metabolic needs. We also discuss the physiology of related subjects such as (1) cardiac output control during exercise, (2) characteristics of heart attacks, and (3) the pain of angina pectoris. BLOOD FLOW REGULATION IN SKELETAL MUSCLE AT REST AND DURING EXERCISE Strenuous exercise is one of the most stressful conditions that the normal circulatory system faces because there is such a large mass of skeletal muscle in the body, all of it requiring large amounts of blood flow. Also, the cardiac output often must increase to four to five times normal in the nonathlete, or to six to seven times normal in the well-trained athlete, to satisfy the metabolic needs of the exercising muscles. RATE OF BLOOD FLOW THROUGH THE MUSCLES During rest, blood flow through skeletal muscle averages 3 to 4 ml/min/100 g of muscle. During extreme exercise in the well-conditioned athlete, this blood flow can increase 25- to 50-fold, rising to 100 to 200 ml/min/100 g of muscle. Peak blood flows as high as 400 ml/min/100 g of muscle have been reported in thigh muscles of endurance-trained athletes. Blood Flow During Muscle Contractions. Figure 21-1 shows a record of blood flow changes in a calf muscle of a human leg during strong rhythmical muscular exercise. Note that the flow increases and decreases with each muscle contraction. At the end of the contractions, the blood flow remains very high for a few seconds but then returns toward normal during the next few minutes. The cause of the lower flow during the muscle contraction phase of exercise is compression of the blood vessels by the contracted muscle. During strong tetanic contraction, which causes sustained compression of the blood vessels, the blood flow can be almost stopped, but this also causes rapid weakening of the contraction. Increased Blood Flow in Muscle Capillaries During Exercise. During rest, some muscle capillaries have little or no flowing blood, but during strenuous exercise, all the capillaries open. This opening of dormant capillaries diminishes the distance that oxygen and other nutrients must diffuse from the capillaries to the contracting muscle fibers and sometimes contributes a twofold to threefold increased capillary surface area through which oxygen and nutrients can diffuse from the blood to the tissues. CONTROL OF BLOOD FLOW IN SKELETAL MUSCLES Decreased Oxygen in Muscle Greatly Enhances Flow. The tremendous increase in muscle blood flow that occurs during skeletal muscle activity is caused mainly by chemicals acting directly on the muscle arterioles to cause dilation. One of the most important chemical effects is reduction of oxygen in the muscle tissues. When muscles are active they use oxygen rapidly, thereby decreasing the oxygen concentration in the tissue fluids. This in turn causes local arteriolar vasodilation because the arteriolar walls cannot maintain contraction in the absence of oxygen and because oxygen deficiency causes release of vasodilator substances. Adenosine may be an important vasodilator substance, but experiments have shown that even large amounts of adenosine infused directly into a muscle artery cannot increase blood flow to the same extent as during intense exercise and cannot sustain vasodilation in skeletal muscle for more than about 2 hours. Fortunately, even after the muscle blood vessels have become insensitive to the vasodilator effects of adenosine, still other vasodilator factors continue to maintain increased capillary blood flow as long as the exercise continues. These factors include (1) potassium ions, (2) adenosine triphosphate (ATP), (3) lactic acid, and (4) carbon dioxide. We still do not know quantitatively how great a role each of these factors plays in increasing 259 Unit IV The Circulation Blood flow (¥100 ml/min) 40 Rhythmic exercise 20 Calf flow0 010 1618 Minutes Figure 21-1. Effects of muscle exercise on blood flow in the calf of a leg during strong rhythmical contraction. The blood flow was much less during contractions than between contractions. (Modified from Barcroft H, Dornhorst AC: The blood flow through the human calf during rhythmic exercise. J Physiol 109:402, 1949.) muscle blood flow during muscle activity; this subject was discussed in additional detail in Chapter 17. Nervous Control of Muscle Blood Flow. In addition to local tissue vasodilator mechanisms, skeletal muscles are provided with sympathetic vasoconstrictor nerves and (in some species of animals) sympathetic vasodilator nerves as well. Sympathetic Vasoconstrictor Nerves. The sympathetic vasoconstrictor nerve fibers secrete norepinephrine at their nerve endings. When maximally activated, this mechanism can decrease blood flow through resting muscles to as little as one-half to one-third normal. This vasoconstriction is of physiologic importance in attenuating decreases of arterial pressure in circulatory shock and during other periods of stress when it may even be necessary to increase blood pressure. In addition to the norepinephrine secreted at the sympathetic vasoconstrictor nerve endings, the medullae of the two adrenal glands also secrete large amounts of norepinephrine plus even more epinephrine into the circulating blood during strenuous exercise. The circulating norepinephrine acts on the muscle vessels to cause a vasoconstrictor effect similar to that caused by direct sympathetic nerve stimulation. The epinephrine, however, often has a slight vasodilator effect because epinephrine excites more of the beta-adrenergic receptors of the vessels, which are vasodilator receptors, in contrast to the alpha vasoconstrictor receptors excited especially by norepinephrine. These receptors are discussed in Chapter 61. CIRCULATORY READJUSTMENTS DURING EXERCISE Three major effects occur during exercise that are essential for the circulatory system to supply the tremendous blood flow required by the muscles. They are (1) sympathetic nervous system activation in many tissues with consequent stimulatory effects on the circulation, (2) increase in arterial pressure, and (3) increase in cardiac output. Effects of Sympathetic Activation At the onset of exercise, signals are transmitted not only from the brain to the muscles to cause muscle contraction but also into the vasomotor center to initiate sympathetic discharge in many other tissues. Simultaneously, the parasympathetic signals to the heart are attenuated. Therefore, three major circulatory effects result. First, the heart is stimulated to a greatly increased heart rate and increased pumping strength as a result of the sympathetic drive to the heart plus release of the heart from normal parasympathetic inhibition. Second, most of the arterioles of the peripheral circulation are strongly contracted, except for the arterioles in the active muscles, which are strongly vasodilated by the local vasodilator effects in the muscles, as noted earlier. Thus, the heart is stimulated to supply the increased blood flow required by the muscles, while at the same time blood flow through most nonmuscular areas of the body is temporarily reduced, thereby “lending” blood supply to the muscles. This process accounts for as much as 2 L/min of extra blood flow to the muscles, which is exceedingly important when one thinks of a person running for his or her life, when even a fractional increase in running speed may make the difference between life and death. Two of the peripheral circulatory systems, the coronary and cerebral systems, are spared this vasoconstrictor effect because both these circulatory areas have poor vasoconstrictor innervation—fortunately so, because both the heart and the brain are as essential to exercise as are the skeletal muscles. Third, the muscle walls of the veins and other capacitative areas of the circulation are contracted powerfully, which greatly increases the mean systemic filling pressure. As we learned in Chapter 20, this effect is one of the most important factors in promoting increase in venous return of blood to the heart and, therefore, in increasing the cardiac output. Sympathetic Stimulation May Increase Arterial Pressure During Exercise An important effect of increased sympathetic stimulation in exercise is to increase the arterial pressure. This increased arterial pressure results from multiple stimulatory effects, including (1) vasoconstriction of the arterioles and small arteries in most tissues of the body except the brain and the active muscles, including the heart, (2) increased pumping activity by the heart, and (3) a great increase in mean systemic filling pressure caused mainly by venous contraction. These effects, working together, almost always increase the arterial pressure during exercise. This increase can be as little as 20 mm Hg or as great as 80 mm Hg, depending on the conditions under which the exercise is performed. When a person performs 260 Chapter 21 Muscle Blood Flow and Cardiac Output During Exercise exercise under tense conditions but uses only a few muscles, the sympathetic nervous response still occurs. In the few active muscles, vasodilation occurs, but elsewhere in the body the effect is mainly vasoconstriction, often increasing the mean arterial pressure to as high as 170 mm Hg. Such a condition might occur in a person standing on a ladder and nailing with a hammer on the ceiling above. The tenseness of the situation is obvious. Conversely, when a person performs massive wholebody exercise, such as running or swimming, the increase in arterial pressure is often only 20 to 40 mm Hg. This lack of a large increase in pressure results from the extreme vasodilation that occurs simultaneously in large masses of active muscle. Why Is Increased Arterial Pressure During Exercise Important? When muscles are stimulated maximally in a laboratory experiment but without allowing the arterial pressure to rise, muscle blood flow seldom rises more than about eightfold. Yet, we know from studies of marathon runners that muscle blood flow can increase from as little as 1 L/min for the whole body during rest to more than 20 L/min during maximal activity. Therefore, it is clear that muscle blood flow can increase much more than occurs in the aforementioned simple laboratory experiment. What is the difference? Mainly, the arterial pressure rises during normal exercise. Let us assume, for instance, that the arterial pressure rises 30 percent, a common increase during heavy exercise. This 30 percent increase causes 30 percent more force to push blood through the muscle tissue vessels. However, this is not the only important effect; the extra pressure also stretches the walls of the vessels, and this effect, along with the locally released vasodilators and higher blood pressure, may increase muscle total flow to more than 20 times normal. Importance of the Increase in Cardiac Output During Exercise Many different physiologic effects occur at the same time during exercise to increase cardiac output approximately in proportion to the degree of exercise. In fact, the ability of the circulatory system to provide increased cardiac output for delivery of oxygen and other nutrients to the muscles during exercise is equally as important as the strength of the muscles themselves in setting the limit for continued muscle work. For instance, marathon runners who can increase their cardiac outputs the most are generally the ones who have record-breaking running times. Graphical Analysis of the Changes in Cardiac Output During Heavy Exercise. Figure 21-2 shows a graphical analysis of the large increase in cardiac output that occurs during heavy exercise. The cardiac output and venous return curves crossing at point A give the analysis for the normal circulation, and the curves crossing at point B analyze heavy exercise. Note that the great increase in cardiac output requires significant changes in both the 25 B Cardiac output and venous return (L/min) 20 15 TINUIV 10 A5 0 40+4+8+12+16+20+24 Right atrial pressure (mm Hg) Figure 21-2. Graphical analysis of change in cardiac output, venous return, and right atrial pressure with onset of strenuous exercise. Black curves, normal circulation. Red curves, heavy exercise. cardiac output curve and the venous return curve, as follows. The increased level of the cardiac output curve is easy to understand. It results almost entirely from sympathetic stimulation of the heart that causes (1) increased heart rate, often up to rates as high as 170 to 190 beats/min, and (2) increased strength of contraction of the heart, often to as much