an overall increase in sympathetic tone Surrogates of Cardiac Output Exercise testing is frequently performed to assess the ability of the cardiovascular system to increase cardiac output in response to an increased workload However, measurement of cardiac output during exercise is often not practical Direct measurements are too invasive to allow adequate levels of exertion Noninvasive methods are often technically difficult and may be inaccurate in the pathophysiologic states that are encountered in many types of congenitally malformed hearts The presence of obstacles to accurately and reliably measure cardiac output have led to the use of consumption of oxygen as a surrogate of cardiac output in many clinical and research settings.4,18,21 Over a broad range of consumption of oxygen, there is a nearly linear relationship between consumption of oxygen and cardiac output (Fig 23.6) FIG 23.6 Relationship of cardiac output to consumption of oxygen measured in 23 subjects during sitting cycle ergometry These data are from the same subjects shown in Fig 23.3 (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.) Even after a plateau in cardiac output at higher workloads, consumption of oxygen continues to increase as a result of increased oxygen extraction, thereby increasing the arterial–mixed venous content of oxygen difference Consumption of oxygen is determined by the amount of oxygen delivered in the blood that is extracted by the metabolically active tissues During exercise, this extraction is determined by the myoglobin content of the exercising muscle, the isoenzyme characteristics of the muscle, and the physiologic milieu in which the muscle is working.4,18 The physiologic state will have a great impact on the oxygenhemoglobin dissociation curve As previously stated, there are multiple byproducts of muscle metabolism that are released into the intercellular space during exercise, shifting the oxygen-hemoglobin dissociation curve down and to the right.4 The local increase in muscle temperature during exercise also has the same effect The net result is an increase in oxygen unloading to the exercising muscle particularly at high workloads There is therefore an increase in the arterial–mixed venous content of oxygen difference and a continued rise in consumption of oxygen, even in the presence of a flattening or plateauing of the rise in cardiac output near peak exercise.4,18,19 Gender differences are present in the relationship between cardiac output and consumption of oxygen (see Fig 23.6) Females tend to have a somewhat higher cardiac output for any given oxygen consumption, as well as a lower maximal consumption.19 These differences are likely due to the difference in hemoglobin concentration between males and females Females have lower levels of hemoglobin compared with males and therefore have lower arterial oxygen content, necessitating a higher cardiac output to deliver an equivalent quantity of oxygen Lower values in adolescent and adult females manifest clinically in slightly higher cardiac outputs and lower consumption of oxygen at peak exercise It is easy to comprehend how anemia will result in reduced consumption of oxygen and a higher ratio of cardiac output to consumption of oxygen compared with nonanemic states Therefore the use of consumption of oxygen as a surrogate for cardiac output is problematic in the presence of anemia Mitochondrial diseases that impair muscle oxygen utilization and hemoglobinopathies that alter oxygen affinity can have an equivalent effect but are much less common than anemia