exercise This can have implications when trying to interpret studies performed semisupine or supine (e.g., used in some labs to facilitate for stress echocardiography) This can be an important consideration in diagnoses where venous pooling, autonomic function, or limited stroke volume augmentation are particularly relevant, such as postural orthostatic tachycardia syndrome or in the Fontan circulation An increase in heart rate is the primary mechanism for the increased cardiac output at higher work rates This is reflected in the essentially linear relationship between heart rate and consumption of oxygen as work rates increase (see Fig 23.4) Therefore the ability to increase heart rate normally during exercise is essential to achieving a normal aerobic capacity The difference in content of oxygen between the arterial and mixed venous blood gradually widens with increasing work rate and consumption of oxygen, as a result of increased extraction of oxygen by the exercising muscles The by-products of myocytic metabolism, including hydrogen, carbon dioxide, and lactate, all lower the pH, thereby shifting the oxygen-hemoglobin dissociation curve down and rightward, favoring increased unloading of oxygen at the level of the exercising muscle Such unloading is more pronounced at higher intensities of exercise, when the concentration of metabolic by-products is greater This will be discussed in more detail later, in the relationship between consumption of oxygen and cardiac output Distribution of Blood Flow For consumption of oxygen to increase during exercise, it is essential that cardiac output not only increase but that blood flow is preferentially shunted to the exercising muscles (Fig 23.5) At peak exercise, blood flow to exercising muscle may be 80% or more of the total cardiac output The redistribution of blood flow is achieved by a combination of autonomic and metabolic vasoregulatory mechanisms.18 Exercise is essentially a state of increased sympathetic nervous system tone, which is regionally overridden by metabolic vasodilation The increase in sympathetic tone associated with exercise results in a generalized constriction of the precapillary resistance arterioles Simultaneously, the sympathetic tone increases heart rate and cardiac contractility, resulting in increased cardiac output.18–20 Vasodilation occurs at the level of the exercising muscle as a result of local metabolic changes Aerobic and anaerobic metabolism, excitation-contraction coupling, and breakdown of adenosine triphosphate all result in the release of potent vasodilators into the interstitial spaces These vasodilators include free potassium and hydrogen ions, carbon dioxide, lactate, adenosine diphosphate, and inorganic phosphate The result is a profound vasodilation of the vascular bed in the exercising muscles FIG 23.5 Parallel circuits of flow through the various systems of organs, both at rest and during peak exercise Note that the cardiac output increases by approximately fivefold from rest to strenuous exercise In contrast, the relative distribution of flow to the various systems is significantly different from rest to peak exercise In both states, the red squares are proportional to the percentage of cardiac output received by the particular system Note that the flow of blood to the muscle increases from between approximately 15% to 20% of cardiac output at rest to 80% to 85% of the cardiac output at peak exercise (From Astrand P, Rodahl K The Muscle and Its Contraction Textbook of Work Physiology, Physiological Bases of Exercise 3rd ed McGraw-Hill; 1986:12–53.) Vasoconstriction of the splanchnic vascular bed results in either no change or a decrease in flow of blood to the gut and kidneys The effect on the overall peripheral vascular resistance depends on the size of the exercising muscle groups During dynamic exercise, such as running, which uses large muscle groups, the net result is a significant drop in systemic vascular resistance, despite