Endurance exercise training evokes several well-documented cardiovascular adaptations. One of these adaptations is cardiomegaly or cardiac hypertrophy. The proposed research will deal with three unexplored aspects of this training-induced phenomenon. The studies for Year 1 are designed to determine if the cardiac hypertrophy demonstrated by dogs in response to exercise training is influenced by the ability of this species to release erythrocytes from the spleen during strenuous exercise. Hemodynamic and metabolic responses to exercise training will also be examined in splenectomized and spleen-intact dogs in order to determine if these adaptations are likewise affected by the dog's ability to increase the oxygen-carrying capacity of blood during periods of stress. Results should indicate whether, compared to spleen-intact animals, splenectomized dogs more closely represent the manner in which humans respond to exercise training. Year 2 will be devoted to assessing the role of the autonomic nervous system supplying the heart in the development of cardiac hypertrophy. Cardiac, hemodynamic, and metabolic adaptations to exercise training will be compared in cardiac-denervated and sham-operated dogs. The results have potential clinical relevance with regard to the manner in which cardiac transplant patients might respond to endurance exercise training. During Year 3, a series of experiments will be conducted to determine if physiological cardiac hypertrophy evoked by a process other than exercise training can enhance aerobic capacity. Cardiovascular responses to exercise will be compared in dogs before and after the development of volume-overload cardiac hypertrophy. Further, it will be determined if exercise training subsequent to volume overload hypertrophy results in an aerobic capacity greater than that which would be attained with exercise training alone. These latter experiments provide a new approach toward resolving a basic question in exercise physiology, whether the limits to exercise performance are central or peripheral in nature. Each of the projects described provides a starting point from which additional studies can evolve and alternate hypotheses can be tested.