Chapter 9 Kennedy 8th Edition PDF

In this chapter and in HKPropel Cardiovascular Responses to Acute Exercise Heart Rate Stroke Volume Cardiac Output The Fick Equation The Cardiac Response to Exercise Blood Pressure Blood Flow Blood The Integrated Cardiovascular Response to Exercise Audio for figure 9.2 describes the use of a submaxi...

In this chapter and in HKPropel Cardiovascular Responses to Acute Exercise Heart Rate Stroke Volume Cardiac Output The Fick Equation The Cardiac Response to Exercise Blood Pressure Blood Flow Blood The Integrated Cardiovascular Response to Exercise Audio for figure 9.2 describes the use of a submaximal exercise test to estimate maximal exercise capacity. Video 9.1 presents Dr. Ben Levine on physiological differences in trained versus untrained people and the relation between cardiac output and oxygen use. Audio for figure 9.9 describes an example of cardiovascular drift. Animation for figure 9.12 details the integrated cardiovascular response to exercise. Activity 9.1 Cardiovascular Response to Exercise reviews cardiovascular changes occurring during exercise. Activity 9.2 Cardiovascular Response Scenarios explores how cardiovascular responses contribute to real-life situations. Respiratory Responses to Acute Exercise Pulmonary Ventilation During Dynamic Exercise Breathing Irregularities During Exercise Ventilation and Energy Metabolism Respiratory Limitations to Performance Respiratory Regulation of Acid–Base Balance Activity 9.3 Pulmonary Ventilation During Exercise investigates the response of pulmonary ventilation to exercise and the factors that affect the phases of pulmonary ventilation. Activity 9.4 Pulmonary Ventilation and Energy Metabolism reviews the key terms related to pulmonary ventilation and energy metabolism. Recovery From Acute Exercise Cardiovascular Variables During Recovery After Exercise Ventilation During Recovery After Exercise In Closing Completing a full 42.2 km (26.2 mi) marathon is a major accomplishment, even for those who are young and extremely fit. On May 5, 2002, Greg Osterman completed the Cincinnati Flying Pig Marathon, his sixth full marathon, finishing in a time of 5 h and 16 min. This is certainly not a world-record time, or even an exceptional time for fit runners. However, in 1990 at the age of 35, Greg had contracted a viral infection that went right to his heart and progressed to heart failure. In 1992, he received a heart transplant. In 1993, his body started rejecting his new heart and he also contracted leukemia, not an uncommon response to the antirejection drugs given to transplant patients. He miraculously recovered and started his quest to get physically fit. He ran his first race (15K) in 1994, followed by five marathons in Bermuda, San Diego, New York, and Cincinnati (twice) in 1999 and 2001. Greg is an excellent example of both human resolve and physiological adaptability. After reviewing the basic anatomy and physiology of the cardiovascular and respiratory systems, this chapter looks specifically at how these systems respond to the increased demands placed on the body during an acute bout of exercise. With exercise, oxygen demand by the active muscles increases significantly. Metabolic processes speed up and more waste products are created. During prolonged exercise or exercise in a hot environment, body temperature increases. In intense exercise, H+ concentration increases in the muscles and blood, lowering their pH. Cardiovascular Responses to Acute Exercise Numerous interrelated cardiovascular changes occur during dynamic exercise. The primary goal of these adjustments is to increase blood flow to working muscle; however, cardiovascular control of virtually every tissue and organ in the body is also altered. To better understand the changes that occur, we must examine the function of both the heart and the peripheral circulation. In this section, we examine changes in all components of the cardiovascular system from rest to acute exercise, looking specifically at the following: Heart rate Stroke volume Cardiac output Blood pressure Blood flow The blood We then see how these changes are integrated to maintain adequate blood pressure and provide for the exercising body’s needs. Heart Rate Heart rate (HR) is one of the simplest physiological responses to measure and yet one of the most informative in terms of cardiovascular stress and strain. Measuring HR involves simply taking the subject’s pulse, usually at the radial or carotid artery. Heart rate is a good indicator of relative exercise intensity. Resting Heart Rate Resting heart rate (RHR) averages 60 to 80 beats/min in most individuals. In highly conditioned endurance-trained athletes, resting rates as low as 28 beats/min have been reported. The mechanisms underlying this traininginduced reduction in RHR were covered in chapter 7. Resting heart rate can also be affected by environmental factors; for example, it increases with extremes in temperature and altitude. Just before the start of exercise, preexercise HR usually increases above normal resting values. This is called the anticipatory response. This response is mediated through release of the neurotransmitter norepinephrine from the sympathetic nervous system and the hormone epinephrine from the adrenal medulla. Vagal tone also decreases. Because preexercise HR is elevated, reliable estimates of the true RHR should be made only under conditions of total relaxation, such as early in the morning before the subject rises from a restful night’s sleep. Heart Rate During Exercise When exercise begins, HR increases directly in proportion to the increase in exercise intensity (see figure 9.1), until near-maximal exercise is achieved. As maximal exercise intensity is approached, HR begins to plateau even as the exercise workload continues to increase. This indicates that HR is approaching a maximal value. The maximal heart rate (HRmax) is the highest HR value achieved in an all-out effort to the point of volitional fatigue. Once accurately determined, HRmax is a highly reliable value that remains constant from day to day. HRmax is commonly used in clinical exercise testing and to prescribe exercise intensity in physical training and rehabilitation settings. However, this value changes slightly from year to year owing to a normal age-related decline. FIGURE 9.1 Changes in heart rate (HR) as a subject progressively walks, jogs, and then runs on a treadmill as intensity is increased. Heart rate is plotted against exercise intensity, shown as a percentage of the subject’s O2max, at which point the rise in HR begins to plateau. The HR at this plateau is the subject’s maximal HR, or HRmax. An exercise test to maximal exertion may not always be feasible, especially in clinical settings where maximal exercise may not be safe or in field tests where advanced equipment (such as a treadmill or stationary bicycle with adjustable grade or resistance) may not be available. Because of these limitations, there is a need for accurate equations to predict HRmax. It is often estimated based on age because HRmax shows a slight but predictable decrease of about one beat per year beginning at 10 to 15 years of age. The most commonly used approximation of one’s predicted HRmax is HRmax = 220 − age (years) However, this is only an estimate—individual values vary considerably from this average value. To illustrate, for a 40-year-old woman, HRmax would be estimated to be 180 beats/min (HRmax = 220 − 40 beats/min). However, 68% of all 40-year-olds have actual HRmax values between 168 and 192 beats/min (mean ± 1 standard deviation), and 95% fall between 156 and 204 beats/min (mean ± 2 standard deviations). This demonstrates the potential for error in estimating a person’s HRmax. Furthermore, the equation HRmax = 220 − age has been shown to overestimate HRmax in young individuals, best predict actual HRmax in individuals around age 40, and increasingly underestimate HRmax as people age.8 More accurate equations have been developed from large population studies to estimate HRmax from age, including HRmax = 208 − (0.7 × age)16 and HRmax = 211 − (0.64 × age)8 When the exercise intensity is held constant at any submaximal workload, HR increases fairly rapidly until it reaches a plateau. This plateau is the steady-state heart rate, and it is the optimal HR for meeting the circulatory demands at that specific rate of work. For each subsequent increase in intensity, HR will reach a new steady-state value within 3 min. However, the more intense the exercise, the longer it takes to achieve this steady-state value. The concept of steady-state heart rate forms the basis for simple exercise tests that have been developed to estimate cardiorespiratory (aerobic) fitness. In one such test, individuals are placed on an exercise device, such as a cycle ergometer, and asked to perform exercise at two or three standardized exercise intensities. Those with better cardiorespiratory endurance capacity will have a lower steady-state HR at each exercise intensity than those who are less fit. Thus, a lower steady-state HR at a fixed exercise intensity is a valid predictor of better cardiorespiratory fitness. Figure 9.2 illustrates results from a submaximal graded exercise test performed on a cycle ergometer by two different individuals of the same age. Steady-state HR is measured at three or four distinct workloads, and a line of best fit is drawn through the data points. Because there is a consistent relation between exercise intensity and energy demand, steadystate HR can be plotted against the corresponding energy ( O2) required to do work on the cycle ergometer. The resultant line can be extrapolated to the age-predicted HRmax to estimate an individual’s maximal exercise capacity. In this figure, subject A has a higher fitness level than subject B because (1) at any given submaximal intensity, this subject’s HR is lower and (2) extrapolation to age-predicted HRmax yields a higher estimated maximal exercise capacity (O2max). Heart Rate Variability Heart rate variability is a measure of the rhythmic fluctuation in HR that occurs because of continuous changes in the sympathetic– parasympathetic balance that controls sinus rhythm. Analysis of HR variability has been used as a method of noninvasively evaluating the relative contributions of the sympathetic and parasympathetic nervous systems at rest and during exercise. During acute aerobic exercise, many different factors contribute to increasing HR variability, including increases in body core temperature, sympathetic nerve activity, and respiratory rate. After a bout of acute exercise, HR variability gradually increases compared against preexercising values because of greater vagal tone. Moreover, changes in HR variability can be used to assess the impact of exercise training (discussed in chapter 12), the occurrence of overtraining15 (discussed in chapter 16), and even as a diagnostic tool in certain clinical populations12 (discussed in chapter 22). FIGURE 9.2 The increase in heart rate with increasing power output on a cycle ergometer and increasing oxygen uptake is linear within a wide range. The predicted maximal oxygen uptake can be extrapolated using the subject’s estimated maximal heart rate as demonstrated here for two subjects with similar estimated maximal heart rates but quite different maximal workloads and O2max values. Reprinted from P.O. Åstrand et al., Textbook of Work Physiology: Physiological Bases of Exercise, 4th ed. (Champaign, IL: Human Kinetics, 2003), 285. Heart rate, like other signals that repeat periodically over time, can be represented by a power spectrum, which describes how much of the signal occurs at each different frequency. HR signals are analyzed with respect to frequency, rather than time, using a mathematical technique called spectral analysis. In spectral analysis, the variability around the mean HR is separated into the contributing frequency domains. There are many physiological influences on HR variability frequency domains.5 Mathematically separating these different elements of HR variability allows researchers to examine the impact of exercise training or disease on each one of the individual contributors. For example, with aerobic exercise training, there is an increase in the parasympathetic control of HR, characterized by greater vagal tone and reduced resting sympathetic nerve activity, which affects the high-frequency domain of HR variability. Stroke Volume Stroke volume (SV) also changes during acute exercise to allow the heart to meet the demands of exercise. At near-maximal and maximal exercise intensities, as HR approaches its maximum, SV is a major determinant of cardiorespiratory endurance capacity. Stroke volume is determined by four factors: The volume of venous blood returned to the heart (the heart can only pump what returns) Ventricular distensibility (the capacity to enlarge the ventricle, to allow maximal filling) Ventricular contractility (the inherent capacity of the ventricle to contract forcefully) Aortic or pulmonary artery pressure (the pressure against which the ventricles must contract) The first two factors influence the filling capacity of the ventricle, determining how much blood fills the ventricle and the ease with which the ventricle is filled at the available pressure. Together, these factors determine the end-diastolic volume (EDV), sometimes referred to as the preload. The last two characteristics influence the ventricle’s ability to empty during systole, determining the force with which blood is ejected and the pressure against which it must be expelled into the arteries. The latter factor, the aortic mean pressure, which represents resistance to blood being ejected from the left ventricle (and to a less important extent, the pulmonary artery pressure resistance to flow from the right ventricle), is referred to as the afterload. These four factors combine to determine the SV during acute exercise. Stroke Volume During Exercise Stroke volume increases above resting values during exercise. Most researchers agree that SV increases with increasing exercise intensity up to intensities somewhere between 40% and 60% of O2max. At that point, SV typically plateaus, remaining essentially unchanged up to and including the point of exhaustion, as shown in figure 9.3. However, other researchers have reported that SV continues to increase beyond 40% to 60% O2max, even up through maximal exercise intensities, as discussed shortly. When the body is in an upright position, SV can approximately double from resting to maximal values. For example, in active but untrained individuals, SV increases from about 60 to 70 ml/beat at rest to 110 to 130 ml/beat during maximal exercise. In highly trained endurance athletes, SV can increase from 80 to 110 ml/beat at rest to 160 to 200 ml/beat during maximal exercise. During supine exercise, such as recumbent cycling, SV also increases but usually by only about 20% to 40%—not nearly as much as in an upright position. Why does body position make such a difference? FIGURE 9.3 Changes in stroke volume (SV) as a subject exercises on a treadmill at increasing intensities. Stroke volume is plotted as a function of percent O2max. The SV increases with increasing intensity up to approximately 40% to 60% of O2max, before reaching a maximum (SVmax). When the body is in the supine position, blood does not pool in the lower extremities. Blood returns more easily to the heart in a supine posture, which means that resting SV values are higher in the supine position than in the upright position. Thus, the increase in SV with maximal exercise is not as great in the supine position as in the upright position because SV starts out higher. Interestingly, the highest SV attainable in upright exercise is only slightly greater than the resting value in the reclining position. The majority of the SV increase during low to moderate intensities of exercise in the upright position appears to be compensating for the force of gravity that causes blood to pool in the extremities. Although researchers agree that SV increases as exercise intensity increases up to approximately 40% to 60% O2max, reports about what happens after that point differ. A few studies have shown that SV continues to increase beyond that intensity. Part of this apparent disagreement might result from differences among studies in the mode of exercise testing. Studies that show plateaus in the 40% to 60% O2max range typically have used cycle ergometers as the mode of exercise. This makes intuitive sense since blood is pooled in the legs during cycle ergometer exercise, resulting in decreased venous return of blood from the legs. Thus, the plateau in SV might be unique to cycling exercise. Alternatively, in those studies in which SV continued to increase up to maximal exercise intensities, subjects were generally highly trained athletes. Many highly trained athletes, including highly trained cyclists tested on a cycle ergometer, can continue to increase their SV beyond 60% O2max, perhaps because of adaptations caused by aerobic training. One such adaptation is an increased venous return, which leads to better ventricular filling, and an increased force of contraction (FrankStarling mechanism). The increases in cardiac output and SV with increasing work as represented by increasing HR, in elite athletes, trained university distance runners, and untrained university students, are illustrated in figure 9.4. FIGURE 9.4 Cardiac output and stroke volume responses to increasing exercise intensities measured in untrained subjects, trained distance runners, and elite runners. Adapted by permission from B. Zhou et al., “Stroke Volume Does Not Plateau During Graded Exercise in Elite Male Distance Runners,” Medicine and Science in Sports and Exercise 33 (2001): 1849-1854. Importance of Stroke Volume to O2max O2max is widely regarded as the single best measure of cardiorespiratory endurance, as discussed in chapter 5. At a maximal exercise intensity, O2max defines the upper limit of cardiovascular function. That is, O2max = HRmax × SVmax × (a-v)O2max Table 9.1 shows the stark difference in O2maxbetween an elite athlete, a normal age-matched subject, and a cardiac patient with mitral stenosis (a narrowing of the mitral valve). Because differences in HRmax and (av)O2max among these three groups are small, it is the ability to increase SV during maximal exercise that primarily determines O2max. How Does Stroke Volume Increase During Exercise? Stroke volume increases during exercise even though there is less time for ventricular filling, especially at high heart rates. For example, at a resting HR of 70 beats/min, filling time between beats is 0.55 s. At a HR of 195 beats/min, this interval decreases to 0.12 s.13 How does SV increase in light of less time to fill? One explanation for the increase in SV with exercise is that the primary factor determining SV is increased preload, or the extent to which the ventricle stretches as it fills with blood (i.e., the EDV). When the ventricle stretches more during filling, it subsequently contracts more forcefully. For example, when a larger volume of blood enters and fills the ventricle during diastole, the ventricular walls stretch to a greater extent. To eject that greater volume of blood, the ventricle responds by contracting more forcefully. This is referred to as the Frank-Starling mechanism. At the level of the muscle fiber, the greater the stretch of the myocardial cells, the more actin–myosin cross-bridges are formed, and greater force is developed. Additionally, SV will increase during exercise if the ventricle’s contractility (an inherent property of the ventricle) is enhanced. Contractility can increase by increasing sympathetic nerve stimulation or circulating catecholamines (epinephrine, norepinephrine), or both. An improved force of contraction can increase SV with or without an increased EDV by increasing the ejection fraction. Finally, when mean arterial blood pressure is low, SV is greater since there is less resistance to outflow into the aorta. These mechanisms all combine to determine the SV at any given intensity of dynamic exercise. Stroke volume is much more difficult to measure than HR. Some clinically used cardiovascular diagnostic techniques have made it possible to determine exactly how SV changes with exercise. Echocardiography (using sound waves) and radionuclide techniques (tagging red blood cells with radioactive tracers) have elucidated how the heart chambers respond to increasing oxygen demands during exercise. With either technique, continuous images of the heart can be taken at rest and up to nearmaximal intensities of exercise. Figure 9.5 illustrates the results of one study of normally active but untrained subjects.9 In this study, participants were tested during both supine and upright cycle ergometry at rest and at three exercise intensities, which are depicted on the x-axis of figure 9.5. When one goes from resting conditions to exercise of increasing intensity, there is an increase in left ventricular EDV (a greater filling or preload), which serves to increase SV through the FrankStarling mechanism. There is also a decrease in the left ventricular ESV (greater emptying), indicating an increased force of contraction. Figure 9.5 shows that both the Frank-Starling mechanism and increased contractility are important in increasing SV during exercise. The FrankStarling mechanism appears to have its greatest influence at lower exercise intensities, and improved contractile force becomes more important at higher exercise intensities. Recall that HR also increases with exercise intensity. The plateau or small decrease in left ventricular EDV at high exercise intensities could be caused by a reduced ventricular filling time due to the high HR. One study showed that ventricular filling time decreased from about 500 to 700 ms at rest to about 150 ms at HRs between 150 and 200 beats/min.17 Therefore, with increasing intensities approaching O2max (and HRmax), the diastolic filling time could be shortened enough to limit filling. As a result, EDV might plateau or even start to decrease. TABLE 9.1 The Importance of Stroke Volume in Determining O2max Group O2max (ml/min) HRmax (beats/min) SVmax (ml/beat) (a-v)O2max (ml/100 ml) Athletes 6,250 190 205 16 Normal subjects 3,500 195 112 16 Cardiac patients 1,400 190 43 17 For the Frank-Starling mechanism to increase SV, left ventricular EDV must increase, necessitating an increased venous return to the heart. As discussed in chapter 7, the muscle pump and respiratory pump both aid in increasing venous return. In addition, redistribution of blood flow and volume from inactive tissues such as the splanchnic and renal circulations increases the available central blood volume. FIGURE 9.5 Changes in left ventricular end-diastolic volume (EDV), endsystolic volume (ESV), and stroke volume (SV) at rest and during low-, intermediate-, and peak-intensity exercise when the subject is in the (a) supine and (b) upright positions. Note that SV = EDV − ESV. Adapted from Poliner et al. (1980). To review, two factors that can contribute to an increase in SV with increasing intensity of exercise are increased venous return (preload) and increased ventricular contractility. The third factor that contributes to the increase in SV during exercise—a decrease in afterload—results from a decrease in total peripheral resistance. Total peripheral resistance (TPR) decreases because of vasodilation of the blood vessels in exercising skeletal muscle. This decrease in afterload allows the left ventricle to expel blood against less resistance, facilitating greater emptying of the ventricle. Cardiac Output Since cardiac output is the product of heart rate and stroke volume (= HR × SV), cardiac output predictably increases with increasing exercise intensity (see figure 9.6). Resting cardiac output is approximately 5.0 L/min but varies in proportion to the size of the person. Maximal cardiac output varies between less than 20 L/min in sedentary individuals to 40 or more L/min in elite endurance athletes. Maximal is a function of both body size and endurance training. The linear relation between cardiac output and exercise intensity is expected because the major purpose of the increase in cardiac output is to meet the muscles’ increased demand for oxygen. Like O2max, when cardiac output approaches maximal exercise intensity, it may reach a plateau (see figure 9.6). In fact, it is likely that O2max is ultimately limited by the inability of cardiac output to increase further. VIDEO 9.1 Dr. Ben Levine on physiological differences in trained versus untrained people and the relation between cardiac output and oxygen use. FIGURE 9.6 The cardiac output () response to walking–running on a treadmill at increasing intensities plotted as a function of percent O2max. Cardiac output increases in direct proportion to increasing intensity, eventually reaching a maximum (max). The Fick Equation In the 1870s, a cardiovascular physiologist by the name of Adolph Fick developed a principle critical to our understanding of the basic relation between metabolism and cardiovascular function. In its simplest form, the Fick principle states that the oxygen consumption of a tissue is dependent on blood flow to that tissue and the amount of oxygen extracted from the blood by the tissue. This principle can be applied to the whole body or to regional circulations. Oxygen consumption is the product of blood flow and the difference in concentration of oxygen in the blood between the arterial blood supplying the tissue and the venous blood draining out of the tissue—the (a-v)O2 difference. Whole-body oxygen consumption (O2) is calculated as the product of the cardiac output () and (a-v)O2 difference. Fick equation: O2 = × (a-v)O2 difference It can be rewritten as O2 = HR × SV × (a-v)O2 difference This basic relation is an important concept in exercise physiology and comes up frequently throughout the remainder of this book. The Cardiac Response to Exercise To see how HR, SV, and vary under various conditions of rest and exercise, consider the following example. An individual first moves from a reclining position to a seated posture and then to standing. Next the person begins walking, then jogging, and finally breaks into a fast-paced run. How does the heart respond? In a reclining position, HR is ~50 beats/min; it increases to about 55 beats/min during sitting and to about 60 beats/min during standing. When the body shifts from a reclining to a sitting position and then to a standing position, gravity causes blood to pool in the legs, which reduces the volume of blood returning to the heart and thus decreases SV. To compensate for the reduction in SV, HR increases in order to maintain cardiac output; that is, = HR × SV. During the transition from rest to walking, HR increases from about 60 to about 90 beats/min. Heart rate increases to 140 beats/min with moderatepaced jogging and can reach 180 beats/min or more with a fast-paced run. The initial increase in HR—up to about 100 beats/min—is mediated by a withdrawal of parasympathetic (vagal) tone. Further increases in HR are mediated by increased activation of the sympathetic nervous system. Stroke volume also increases with exercise, further increasing cardiac output. These relations are illustrated in figure 9.7. RESEARCH PERSPECTIVE 9.1 Exercise After a High-Salt Meal Consuming a high-sodium (Na+) diet has been linked with an increased risk of cardiovascular disease. Unfortunately, most Americans eat much more than the recommended amount of Na+ each day (1,500 mg), and alarmingly, it is not uncommon to exceed this amount of Na+ in a single meal! A single high-salt meal has negative consequences for vascular health and autonomic function, both of which may influence the control of blood pressure during exercise. Interestingly, a recent study investigated whether a single high Na+ meal augmented the blood pressure response to dynamic exercise in healthy normotensive adults (Migdal et al., 2020). In a randomized, double-blind crossover study, participants completed two laboratory visits: during one, they consumed a high Na+ meal (1,495 mg) and during the other, they consumed a low Na+ meal (138 mg). Eighty minutes after meal consumption, participants completed a graded maximal exercise test on a cycle ergometer. As expected, the high Na+ meal increased serum Na+ concentration and plasma osmolality compared with the low Na+ meal. Neither peak exercise intensity nor rating of perceived exertion were different between conditions. Further, there were no differences in the blood pressure response to dynamic exercise following high and low salt consumption. Taken together, these data indicate that despite increases in serum Na+ concentration, consumption of a single high Na+ meal does not adversely affect the blood pressure response to whole-body dynamic exercise in healthy normotensive adults. Migdal, K.U., Robinson, A.T., Watso, J.C., Babcock, M.C., Serrador, J.M., & Farquhar, W.B. (2020). A high salt meal does not augment blood pressure responses during maximal exercise. Applied Physiology, Nutrition, and Metabolism, 45(2), 123-128. https://doi.org/10.1139/apnm-2019-0217 During the initial stages of exercise in untrained individuals, increased cardiac output is caused by an increase in both HR and SV. When the level of exercise exceeds 40% to 60% of the individual’s maximal exercise capacity, SV either plateaus or continues to increase at a much slower rate. Thus, further increases in cardiac output are largely the result of increases in HR. Further SV increases contribute more to the rise in cardiac output at high intensities of exercise in highly trained athletes. FIGURE 9.7 Changes in (a) heart rate, (b) stroke volume, and (c) cardiac output with changes in posture (lying supine, sitting, and standing upright) and with exercise (walking at 5 km/h [3.1 mph], jogging at 11 km/h [6.8 mph], and running at 16 km/h [9.9 mph]). Blood Pressure During endurance exercise, systolic blood pressure increases in direct proportion to the increase in exercise intensity. However, diastolic pressure does not change significantly and may even decrease. As a result of the increased systolic pressure, mean arterial blood pressure increases. A systolic pressure that starts out at 120 mmHg in a normal, healthy person at rest can exceed 200 mmHg at maximal exercise. Systolic pressures of 240 to 250 mmHg have been reported in normal, healthy, highly trained athletes at maximal intensities of aerobic exercise. Increased systolic blood pressure results from the increased cardiac output that accompanies increasing rates of work. This increase in pressure helps facilitate the increase in blood flow through the vasculature. Also, blood pressure (i.e., hydrostatic pressure) in large part determines how much plasma leaves the capillaries, entering the tissues and carrying needed supplies. Thus increased systolic pressure aids substrate delivery to working muscles. After increasing initially, mean arterial pressure reaches a steady state during submaximal steady-state endurance exercise. As work intensity increases, so does systolic blood pressure. If steady-state exercise is prolonged, the systolic pressure might start to decrease gradually, but diastolic pressure remains constant. The slight decrease in systolic blood pressure, if it occurs, is a normal response and simply reflects increased vasodilation in the active muscles, which decreases the total peripheral resistance (since mean arterial pressure = cardiac output × total peripheral resistance). Diastolic blood pressure changes little during submaximal dynamic exercise; however, at maximal exercise intensities, diastolic blood pressure may increase slightly. Remember that diastolic pressure reflects the pressure in the arteries when the heart is at rest (diastole). With dynamic exercise there is an overall increase in sympathetic tone to the vasculature, causing overall vasoconstriction. However, this vasoconstriction is blunted in the exercising muscles by the release of local vasodilators, a phenomenon called functional sympatholysis (discussed in chapter 7). Thus, because there is a balance between vasoconstriction to inactive regional circulations and vasodilation in active skeletal muscle, diastolic pressure does not change substantially. However, in some cases of cardiovascular disease, increases in diastolic pressure of 15 mmHg or more occur in response to exercise and are one of several indications for immediately stopping a diagnostic exercise test. Upper body exercise causes a greater blood pressure response than leg exercise at the same absolute rate of energy expenditure. This is most likely attributable to the smaller exercising muscle mass of the upper body compared with the lower body, plus an increased energy demand to stabilize the upper body during arm exercise. This difference in the systolic blood pressure response to upper and lower body exercise has important implications for the heart. Myocardial oxygen uptake and myocardial blood flow are directly related to the product of HR and systolic blood pressure (SBP). This value is referred to as the rate– pressure product (RPP), or double product (RPP = HR × SBP). With static or dynamic resistance exercise or upper body dynamic exercise, the RPP is elevated, indicating increased myocardial oxygen demand. The use of RPP as an indirect index of myocardial oxygen demand is important in clinical exercise testing. Periodic blood pressure increases during resistance exercise, such as weightlifting, can be extreme. With high-intensity resistance training, blood pressure can briefly reach 480/350 mmHg. Very high pressures like these are more commonly seen when the exerciser performs a Valsalva maneuver to aid heavy lifts. This maneuver occurs when a person tries to exhale while the mouth, nose, and glottis are closed. This action causes an enormous increase in intrathoracic pressure. Much of the subsequent blood pressure increase results from the body’s effort to overcome the high internal pressures created during the Valsalva maneuver. Blood Flow Acute increases in cardiac output and blood pressure during exercise allow for increased total blood flow to the body. These responses facilitate increased blood to areas where it is needed, primarily the exercising muscles. Additionally, sympathetic control of the cardiovascular system redistributes blood so that areas with the greatest metabolic need receive more blood than areas with low demands. IN REVIEW Preexercise HR is not a reliable estimate of RHR because of the anticipatory HR response. As exercise intensity increases, HR increases proportionately, approaching HRmax near the maximal exercise intensity. To estimate HRmax, the equation HRmax = 220 − age in years is most commonly used. However, HRmax = 208 − (0.7 × age in years) or HRmax = 211 − (0.64 × age in years) may be more accurate. Stroke volume (the amount of blood ejected with each contraction) also increases proportionately with increasing exercise intensity but usually achieves its maximal value at about 40% to 60% of O2max in untrained individuals. Highly trained individuals can continue to increase SV, sometimes up to maximal exercise intensity. Increases in HR and SV combine to increase cardiac output. Thus, more blood is pumped during exercise, ensuring that an adequate supply of oxygen and metabolic substrates reaches the exercising muscles and that the waste products of muscle metabolism are cleared away. During exercise, cardiac output increases in proportion to exercise intensity to match the need for increased blood flow to exercising muscles. According to the Fick equation, whole-body oxygen consumption (O2) is calculated as the product of the cardiac output () and (a-v)O2 difference. The ability to increase cardiac output, predominantly driven by increases in stroke volume, is the primary determinant of O2max. Redistribution of Blood During Exercise Blood flow patterns change markedly in the transition from rest to exercise. Through the vasoconstrictor action of the sympathetic nervous system on local arterioles, blood flow is redirected away from areas where elevated flow is not essential to those areas that are active during exercise (see figure 7.11). Only 15% to 20% of the resting cardiac output goes to muscle, but during high-intensity exercise, the muscles may receive 80% to 85% of the cardiac output. This shift in blood flow to the muscles is accomplished primarily by reducing blood flow to the kidneys and the so-called splanchnic circulation (which includes the liver, stomach, pancreas, and intestines). Figure 9.8 illustrates a typical distribution of cardiac output throughout the body at rest and during heavy exercise.18 Because cardiac output increases greatly with increasing intensity of exercise, the values are shown both as the relative percentage of cardiac output and as the absolute cardiac output going to each regional circulation at rest and at three intensities of exercise. FIGURE 9.8 The distribution of cardiac output at rest and during exercise (a) as a percentage of the total cardiac output and (b) as absolute volumes. Data from Vander, Sherman, and Luciano (1985). Although several physiological mechanisms are responsible for the redistribution of blood flow during exercise, they work together in an integrated fashion. To illustrate this, consider what happens to blood flow during exercise, focusing on the primary driver of the response, namely the increased blood flow requirement of the exercising skeletal muscles. As exercise begins, active skeletal muscles rapidly require increased oxygen delivery. This need is partially met through sympathetic stimulation of vessels in those areas to which blood flow is to be reduced (e.g., the splanchnic and renal circulations). The resulting vasoconstriction in those areas allows for more of the (increased) cardiac output to be distributed to the exercising skeletal muscles. In the skeletal muscles, sympathetic stimulation to the constrictor fibers in the arteriolar walls also increases; however, local dilator substances are released from the exercising muscle and overcome sympathetic vasoconstriction, producing an overall vasodilation in the muscle (functional sympatholysis). Many local dilator substances are released in exercising skeletal muscle. As the metabolic rate of the muscle tissue increases during exercise, metabolic waste products begin to accumulate. Increased metabolism causes an increase in acidity (increased hydrogen ions and lower pH), carbon dioxide, and temperature in the muscle tissue. These are some of the local changes that trigger vasodilation of, and increasing blood flow through, the arterioles feeding local capillaries. Local vasodilation is also triggered by the low partial pressure of oxygen in the tissue or a reduction in oxygen bound to hemoglobin (increased oxygen demand), the act of muscle contraction, and possibly other vasoactive substances (including adenosine) released as a result of skeletal muscle contraction. When exercise is performed in a hot environment, there is also an increase in blood flow to the skin to help dissipate the body heat. The sympathetic control of skin blood flow is unique in that there are sympathetic vasoconstrictor fibers (similar to skeletal muscle) and sympathetic active vasodilator fibers interacting over most of the skin surface area. During dynamic exercise, as body core temperature rises, there is initially a reduction in sympathetic vasoconstriction, causing a passive vasodilation. Once a specific body core temperature threshold is reached, skin blood flow begins to dramatically increase by activation of the sympathetic active vasodilator system. The increase in skin blood flow during exercise promotes heat loss, because metabolic heat from deep in the body can be released only when blood moves close to the skin. This limits the rate of rise in body temperature, as discussed in more detail in chapter 14. RESEARCH PERSPECTIVE 9.2 The Influence of Exercise on Red Blood Cell Function Red blood cell (RBC) physiology and the flow of blood are critical for adequate tissue perfusion at rest and during exercise. Alterations in RBC rheological properties (i.e., deformability) during exercise may increase blood viscosity, thus potentially influencing blood flow and exercise performance. During cycling exercise, the majority of studies report an increase in blood viscosity secondary to a decrease in RBC deformability and an increase in hematocrit. The decrease in RBC deformability may result from the exercise-induced increases in lactate and oxidative stress. Studies have demonstrated that incubation of RBCs with oxidant agents promotes eryptosis (RBC apoptosis), ultimately leading to RBC shrinkage and membrane blebbing or bulging outward. Given the increases in lactate, oxidative stress, and shear that occur during exercise, it is somewhat surprising that RBC rheology and function during running exercise have not yet been elucidated. This was the focus of a 2020 pilot study (Nader et al.). Eight endurance-trained athletes performed a 10 km (6.2 mi) run at maximal intensity. Blood was sampled before and after the running exercise to measure lactate and glucose, hematological and hemorheological parameters (blood viscosity, RBC deformability, and aggregation), eryptosis markers, RBC-derived microparticles, and RBC electrophysiology. Running exercise decreased blood viscosity via increases in RBC deformability, which occurred through rehydration processes and volume regulation. Further, running did not appear to influence the RBC senescence (i.e., aging) process and did not cause any RBC damage. It is tempting to speculate that the running-induced reduction in blood viscosity could decrease blood flow resistance, thereby optimizing muscle oxygenation and performance. However, in adults with normal vascular function, somewhat paradoxically, increased blood viscosity induces vasodilation and increased tissue perfusion, likely due to greater shear stress–mediated nitric oxide production. Determining the downstream effects of blood viscosity in terms of muscle perfusion and performance during running exercise will require future studies. Nader, E., Monedero, D., Robert, M., Skinner, S., Stauffer, E., Cibiel, A., Germain, M., Hugonnet, J., Scheer, A., Joly, P., Renoux, C., Connes, P., & Égée, S. (2020). Impact of a 10 km running trial on eryptosis, red blood cell rheology, and electrophysiology in endurance trained athletes: A pilot study. European Journal of Applied Physiology, 120(1), 255-266. https://doi.org/10.1007/s00421-019-04271-x Cardiovascular Drift With prolonged aerobic exercise or aerobic exercise in a hot environment at a steady-state intensity, SV gradually decreases and HR increases. Cardiac output is well maintained, but arterial blood pressure also declines. These alterations, illustrated in figure 9.9, have been referred to collectively as cardiovascular drift. Cardiovascular drift has traditionally been associated with a progressive increase in the fraction of cardiac output directed to the vasodilated skin to facilitate heat loss and attenuate the increase in body core temperature. With more blood in the skin for the purpose of cooling the body, less blood is available to return to the heart, thus decreasing preload. There is also a small decrease in blood volume resulting from sweating and from a generalized shift of plasma across the capillary membrane into the surrounding tissues. These factors combine to decrease ventricular filling pressure, which decreases venous return to the heart and reduces the EDV. With the reduction in EDV, SV is reduced (SV = EDV − ESV). In order to maintain cardiac output (= HR × SV), HR increases to compensate for the decrease in SV. FIGURE 9.9 Circulatory responses to prolonged, moderately intense exercise in the upright posture in a thermoneutral 20 °C (68 °F) environment, illustrating cardiovascular drift. Values are expressed as the percentage of change from the values measured at the 10 min point of the exercise. Adapted by permission from L.B. Rowell, Human Circulation: Regulation During Physical Stress (New York: Oxford University Press, 1986), 230. A more recent hypothesis has been put forth to explain cardiovascular drift. As HR increases, there is less filling time for the ventricles. This exercise tachycardia may lower SV under the conditions of prolonged exercise even without peripheral displacement of blood volume. From the available research, it is not possible to pinpoint a single hypothesis that fully explains cardiovascular drift, and it is likely that the two mechanisms may interact. Competition for Blood Supply When the demands of exercise are added to blood flow demands for all other systems of the body, competition for a limited available cardiac output can occur. This competition for available blood flow can develop among several vascular beds, depending on the specific conditions. For example, there may be competition for available blood flow between active skeletal muscle and the gastrointestinal system following a meal. McKirnan and coworkers7 studied the effects of feeding versus fasting on the distribution of blood flow during exercise in miniature pigs. The pigs were divided into two groups. One group fasted for 14 to 17 h before exercise. The other group ate their morning ration in two feedings: Half the ration was fed 90 to 120 min before exercise and the other half 30 to 45 min before exercise. Both groups of pigs then ran at approximately 65% of their O2max. Blood flow to the hindlimb muscles during exercise was 18% lower and gastrointestinal blood flow was 23% higher in the fed group than in the fasted group. Similar results in humans suggest that the redistribution of gastrointestinal blood flow to the working muscles is attenuated after a meal. As a practical application, these findings suggest that athletes should be cautious in timing their meals before competition to maximize blood flow to the active muscles during exercise. Another example of the competition for blood flow is seen in exercise in a hot environment. In this scenario, competition for available cardiac output can occur between the skin circulation for thermoregulation and the exercising muscles. This is discussed in more detail in chapter 14. Blood We have now examined how the heart and blood vessels respond to exercise. The remaining component of the cardiovascular system is the blood: the fluid that carries oxygen and nutrients to the tissues and clears away waste products of metabolism. As metabolism increases during exercise, several aspects of the blood itself become increasingly critical for optimal performance. Oxygen Content At rest, the blood’s oxygen content varies from 20 ml of oxygen per 100 ml of arterial blood to 14 ml of oxygen per 100 ml of venous blood returning to the right atrium. The difference between these two values (20 ml − 14 ml = 6 ml) is referred to as the arterial–mixed venous oxygen difference, or (a-v)O2 difference. This value represents the extent to which oxygen is extracted, or removed, from the blood as it passes through the body. With increasing exercise intensity, the (a-v)O2 difference increases progressively and can almost triple from rest to maximal exercise intensities (see figure 9.10). This increased difference really reflects a decreasing venous oxygen content, because arterial oxygen content changes little from rest up to maximal exertion. With exercise, more oxygen is required by the active muscles; therefore, more oxygen is extracted from the blood. The venous oxygen content decreases, approaching zero in the active muscles. However, mixed venous blood in the right atrium of the heart rarely decreases below 4 ml of oxygen per 100 ml of blood because the blood returning from the active tissues is mixed with blood from inactive tissues as it returns to the heart. Oxygen extraction by the inactive tissues is far lower than in the active muscles. FIGURE 9.10 Changes in the oxygen content of arterial and mixed venous blood and the (a-v)O2 difference (arterial–mixed venous oxygen difference) as a function of exercise intensity. Plasma Volume Upon standing, or with the onset of exercise, there is an almost immediate loss of plasma from the blood to the interstitial fluid space. The movement of fluid out of the capillaries is dictated by the pressures inside the capillaries, which include the hydrostatic pressure exerted by increased blood pressure and the oncotic pressure, the pressure exerted by the proteins in the blood, mostly albumin. The pressures that influence fluid movement outside the capillaries are the pressure provided by the surrounding tissue as well as the oncotic pressures from proteins in the interstitial fluid (see figure 9.11). Osmotic pressures, those exerted by electrolytes in solution on both sides of the capillary wall, also play a role. As blood pressure increases with exercise, the hydrostatic pressure within the capillaries increases. This increase in blood pressure forces water from the intravascular compartment to the interstitial compartment. Also, as metabolic waste products build up in the active muscle, intramuscular osmotic pressure increases, which draws fluid out of the capillaries to the muscle. Approximately a 10% to 15% reduction in plasma volume can occur with prolonged exercise, with the largest falls occurring during the first few minutes. During resistance training, the plasma volume loss is proportional to the intensity of the effort, with similar transient losses of fluid from the vascular space of 10% to 15%. If exercise intensity or environmental conditions cause sweating, additional plasma volume losses may occur. Although the major source of fluid for sweat formation is the interstitial fluid, this fluid space will be diminished as sweating continues. This increases the oncotic pressure (since proteins do not move with the fluid) and the osmotic pressure (since sweat has fewer electrolytes than interstitial fluid) in the interstitial space, causing even more plasma to move out of the vascular compartment into the interstitial space. Intracellular fluid volume is impossible to measure directly and accurately, but research suggests that fluid is also lost from the intracellular compartment during prolonged exercise and even from the red blood cells, which may shrink in size. FIGURE 9.11 Filtration of plasma from the microvasculature. Both the blood pressure (PC) inside the blood vessel and the oncotic pressure (πT) in the tissue cause plasma to flow from the intravascular space to the interstitial space. The pressure that the tissue (PT) exerts on the blood vessel and the oncotic pressure of the blood (πC) inside the blood vessel cause plasma to be reabsorbed. Net filtration of plasma can be determined by summing the outward forces (PC + πT) and subtracting the inward forces (PT − πC); net capillary filtration = (PC + πT) − (PT − πC). A reduction in plasma volume can impair performance. For long-duration activities in which dehydration occurs and heat loss is a problem, blood flow to active tissues may be reduced to allow increasingly more blood to be diverted to the skin in an attempt to lose body heat. Note that a decrease in muscle blood flow occurs only in conditions of dehydration and only at high intensities. Severely reduced plasma volume also increases blood viscosity, which can impede blood flow and thus limit oxygen transport, especially if the hematocrit exceeds 60%. In activities that last a few minutes or less, body fluid shifts are of little practical importance. As exercise duration increases, however, body fluid changes and temperature regulation become important for performance. For the football player, the Tour de France cyclist, or the marathon runner, these processes are crucial, not only for competition but also for survival. Deaths have occurred from dehydration and hyperthermia during, or as a result of, various sport activities. These issues are discussed in detail in chapter 14. Hemoconcentration When plasma volume is reduced, hemoconcentration occurs. When the fluid portion of the blood is reduced, the cellular and protein portions represent a larger fraction of the total blood volume; that is, they become more concentrated in the blood. This hemoconcentration increases red blood cell concentration substantially—by up to 25%. Hematocrit can increase from 40% to 50%. However, the total number and volume of red blood cells do not change substantially. The net effect, even without an increase in the total number of red blood cells, is to increase the number of red blood cells per unit of blood; that is, the cells are more concentrated. As the red blood cell concentration increases, so does the blood’s per-unit hemoglobin content. This substantially increases the blood’s oxygen-carrying capacity, which is advantageous during exercise and provides a distinct advantage at altitude, as discussed in chapter 15. The Integrated Cardiovascular Response to Exercise As is evident from all the changes in cardiovascular function that take place during exercise that the cardiovascular system is extremely complex but responds exquisitely to deliver oxygen to meet the demands of exercising muscle. Figure 9.12 is a simplified flow diagram that illustrates how the body integrates all these cardiovascular responses to provide for its needs during exercise. Key areas and responses are labeled and summarized to help illustrate how these complex control mechanisms are coordinated. It is important to note that although the body attempts to meet the blood flow needs of the muscle, it can do so only if blood pressure is not compromised. Maintenance of arterial blood pressure appears to be the highest priority of the cardiovascular system, regardless of exercise, the environment, or other competing needs. FIGURE 9.12 The integrated cardiovascular response to exercise. Adapted from E.F. Coyle, 1991, “Cardiovascular Function During Exercise: Neural Control Factors,” Sports Science Exchange 4, 34 (1991: 1-6. Adapted with permission of Stokely-Van Camp, Inc. The cardiovascular and respiratory adjustments to dynamic exercise are profound and rapid. Within 1 s of the initiation of muscle contraction, HR dramatically increases by vagal withdrawal and respiration increases. Increases in cardiac output and blood pressure increase blood flow to the active skeletal muscle to meet its metabolic demands. What causes these extremely rapid early changes in the cardiovascular system, since they take place well before metabolic needs of working muscle occur? Over the years, there has been considerable debate over what causes the cardiovascular system to be turned on at the onset of exercise. One explanation is the theory of central command, which involves parallel coactivation of both the motor and the cardiovascular control centers of the brain. Activation of central command rapidly increases HR and blood pressure. In addition to central command, the cardiovascular responses to exercise are modified by mechanoreceptors, chemoreceptors, and baroreceptors. As discussed in chapter 7, baroreceptors are sensitive to stretch and send information back to the cardiovascular control centers about blood pressure. Signals from the periphery are sent back to the cardiovascular control centers through the stimulation of mechanoreceptors (sensitive to the stretch of skeletal muscle) and through chemoreceptors (sensitive to an increase in metabolites in the muscle). Feedback about blood pressure and the local muscle environment helps to fine-tune and adjust the cardiovascular response. These relations are illustrated in figure 9.13. Respiratory Responses to Acute Exercise Now that we have discussed the role of the cardiovascular system in delivering oxygen to the exercising muscle, we examine how the respiratory system responds to acute dynamic exercise. Pulmonary Ventilation During Dynamic Exercise The onset of exercise is accompanied by an immediate increase in ventilation. In fact, like the HR response, the marked increase in breathing may occur even before the onset of muscular contractions—that is, it may be an anticipatory response. This is shown in figure 9.14 for light, moderate, and heavy exercise. Because of its rapid onset, this initial respiratory adjustment to the demands of exercise is undoubtedly neural in nature, mediated by respiratory control centers in the brain (central command), although neural signals also come from receptors in the exercising muscle. FIGURE 9.13 A summary of cardiovascular (CV) control during exercise. The more gradual second phase of the respiratory increase shown during heavy exercise in figure 9.14 is controlled primarily by changes in the chemical status of the arterial blood. As exercise progresses, increased metabolism in the muscles generates more CO2 and H+. Recall that these changes shift the oxyhemoglobin saturation curve rightward, enhancing oxygen unloading in the muscles, which increases the (a-v)O2 difference. Increased CO2 and H+ are sensed by chemoreceptors primarily located in the brain, carotid bodies, and lungs, which in turn stimulate the inspiratory center, increasing rate and depth of respiration. Chemoreceptors in the muscles themselves might also be involved. In addition, receptors in the right ventricle of the heart send information to the inspiratory center so that increases in cardiac output can stimulate breathing during the early minutes of exercise. The influences of CO2 and H+ concentrations in the blood on breathing rate and pattern fine-tune the neutrally mediated respiratory response to exercise in order to precisely match oxygen delivery with aerobic demands without overtaxing respiratory muscles. IN REVIEW Mean arterial blood pressure increases immediately in response to exercise, and the magnitude of the increase is proportional to the intensity of exercise. During whole-body endurance exercise, this is accomplished primarily by an increase in systolic blood pressure, with minimal changes in diastolic pressure. Systolic blood pressure can reach, and sometimes exceed 240 to 250 mmHg at maximal exercise intensity, the result of increases in cardiac output. Upper body exercise causes a greater blood pressure response than leg exercise at the same absolute rate of energy expenditure, likely due to the smaller muscle mass involved and the need to stabilize the trunk during dynamic arm exercise. Blood flow is redistributed during exercise from inactive or low-activity tissues of the body like the liver and kidneys to meet the increased metabolic needs of exercising muscles. With prolonged aerobic exercise, or aerobic exercise in the heat, SV gradually decreases and HR increases proportionately to maintain cardiac output. This is referred to as cardiovascular drift and is associated with a progressive increase in blood flow to the vasodilated skin and losses of fluid from the vascular space. The changes that occur in the blood during exercise include the following: The (a-v)O2 difference increases as venous oxygen concentration decreases, reflecting increased extraction of oxygen from the blood for use by the active tissues. Plasma volume decreases. Plasma is pushed out of the capillaries by increased hydrostatic pressure as blood pressure increases, and fluid is drawn into the muscles by the increased oncotic and osmotic pressures in the muscle tissues, a by-product of metabolism. With prolonged exercise or exercise in hot environments, increasingly more plasma volume is lost through sweating. Hemoconcentration occurs as plasma volume (water) decreases. Although the actual number of red