Mechanisms of Anoxic Tolerance in Heart Muscle

将研究动物对环境胁迫的生理生化适应。主要项目涉及淡水龟对缺氧和酸中毒的耐受性，类似于它们在冬季冬眠期间的经历。此外，最近研究了蝙蝠在日常冬眠期间的呼吸和代谢反应，这是这些动物的正常现象。早期对整个动物反应，特别是代谢和血液酸碱反应的研究发现，长期无氧生存是可能的，主要是由于能量代谢的急剧减少，以及从外壳释放碳酸钙对积累的酸的有效缓冲。最近的研究针对的是体外的海龟心脏，在常规组织浴或核磁共振光谱仪中使用灌注的心脏。这些研究表明，在缺氧的情况下，离体心脏可以维持接近正常水平的三磷酸腺苷（ATP）和机械功能，但当缺氧和酸中毒合并时，心脏的机械功能就会衰竭。目前的一个目标是了解这是否真的是“失败”，还是在这些条件下能够生存的适应性功能停止。其他当前的目标包括确定细胞机制的酸碱控制，离子平衡和代谢调节的基础，这些动物的非凡行为。

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.