ABSTRACT
Normal subjects undergoing a CPET ordinarily describe leg muscle fatigue as their primary exercise-limiting symptom. While this sensation of muscle failure could be attributed to primary contractile failure, to inadequate oxygen delivery to muscle, or to inadequate fuel mobilization within muscle, experiments have demonstrated that any intervention that improves the flow of oxygenated blood to exercising muscle will improve maximal oxygen uptake and prolong CPET exercise time. The fuel sources utilized during a CPET are from muscle stores of fatty acids and glycogen, with fatty acids serving as a primary fuel source early in exercise, with progressively increasing dependence on mobilized muscle glycogen at the highest levels of exercise. The primary source of ATP generation in muscle during exercise is the mitochondrial oxidation of those two fuel sources by aerobic metabolism. With the onset of heavy exercise, additional ATP for muscle contraction is generated by accelerated glycolysis, but in the absence of a proportional increase in oxygen delivery, this process also leads to the accumulation of hydrogen ions and lactate, leading to the progressive metabolic acidosis associated with heavy exercise. The time within a CPET marking the onset of that metabolic acidosis is a further augmentation of exercise ventilation that is described as the ventilatory (or anaerobic) threshold.
