The specific aim of this study is to understand the energetic and regulatory mechanisms that permit hearts of hypoxia tolerant vertebrates to function under conditions of hypoxia and acidosis that are rapidly fatal to hearts from hypoxia sensitive animals. Two sets of direct comparisons are planned at appropriate physiologic temperatures: (l) the hypoxia tolerant painted turtle (Chrysemys picta belli) compared to the more hypoxia sensitive softshelled turtle (Trionyx spinifer) at 20 degrees C; and (2) the hypoxia tolerant neonatal rabbit compared to the highly hypoxia sensitive adult rabbit at 38 degrees C. Classic in vitro physiologic and biochemical methods along with nuclear magnetic resonance spectroscopy will be used to examine pH and ionic regulation, cardiac energy state, and myocardial metabolic rate in isolated hearts from these animal models during hypoxia and acidosis and during recovery. These experiments will test the hypotheses that key adaptations to hypoxia and acidosis include reduced cellular energy metabolism, effective cell pH regulation, and effective cell calcium and sodium homeostasis. Studies of extreme hypoxia are severely limited in adult mammalian preparations because of their rapidly failing function. Painted turtles, because of their remarkable adaptations are an exceptional model system for studying these fundamental problems. Neonatal mammals, while less hypoxia tolerant than turtles, are still far better able to deal with the stresses of extreme hypoxia and acidosis than are adults. Many human pathologic conditions result in hypoxic and acidotic insults to the heart and it would be of-great clinical value to develop methods of protecting this sensitive tissue from the deleterious effects of these stresses. The potential significance of this research is that lessons learned from hypoxia tolerant hearts can provide a more fundamental understanding of the limitations of the human heart to hypoxia and acidosis and can suggest rational strategies for counteracting them in clinical, surgical, or organ bank settings.