Mechanisms of Anoxic Tolerance in Heart Muscle

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The physiological and biochemical adaptations of animals to environmental stresses will be studied. The major project concerns the tolerance of freshwater turtles to anoxia and acidosis similar to what they experience during their winter hibernation period. In addition, the respiratory and metabolic responses of bats during daily torpor, a normal occurrence in these animals, has recently been studied. Earlier work on whole animal responses, particularly metabolic and blood acid-base responses, found that long-term survival without oxygen is possible mainly due to a drastic reduction in energy metabolism, and to a lesser extent to effective buffering of accumulated acids by release of calcium carbonate from the shell. Recent research has been directed to the turtle heart in vitro, using perfused hearts either in a conventional tissue bath or in an NMR spectrometer. These studies have revealed that the isolated heart can maintain near normal levels of adenosine triphosphate (ATP) and mechanical function for many hours of anoxia, but when anoxia and acidosis are combined, the heart fails mechanically. One current objective is to learn whether this is really 'failure' or whether instead it is an adaptive arrest of function that enables survival under these conditions. Other current objectives involve defining cellular mechanisms of acid-base control, ion balance, and metabolic regulation that underlie the extraordinary behavior of these animals.