Goodwin G W, Taegtmeyer H
Department of Internal Medicine, University of Texas Houston Medical School 77030.
Am J Physiol. 1994 Aug;267(2 Pt 2):H462-70. doi: 10.1152/ajpheart.1994.267.2.H462.
Functional recovery following ischemia and reperfusion in the isolated working rat heart perfused with glucose (11 mM) was examined in relation to pre- and postischemic levels of ATP, glycogen, glucose 6-phosphate, and the lactate-to-pyruvate ratio. The following variables were studied: feeding and fasting in vivo, addition of L-lactate (10 mM), dl-beta-hydroxybutyrate (10 mM), glucagon (0.01 and 1 micrograms/ml), and a 15-min anoxic perfusion before ischemia in vitro. Recovery was assessed as the percentage of preischemic power. Good correlation was found between functional recovery and the postischemic content of glycogen. Glycogen depletion by anoxia or glucagon before ischemia impaired recovery. There was no relationship among lactate produced, or the lactate-to-pyruvate ratio, and recovery. The addition of lactate or beta-hydroxybutyrate to hearts from fed rats increased the content of glycogen and glucose 6-phosphate, whereas addition of lactate, but not beta-hydroxybutyrate, improved recovery. There was a linear relationship between glycogen content and glucose 6-phosphate levels. In conclusion, the degree of return of oxidative metabolism and of net glycogen resynthesis reflects postischemic recovery of function. The results also suggest a role for anaplerosis of the citric acid cycle as an additional determinant of postischemic recovery.
在灌注葡萄糖(11 mM)的离体工作大鼠心脏中,研究了缺血再灌注后的功能恢复与缺血前后ATP、糖原、6-磷酸葡萄糖水平以及乳酸与丙酮酸比值之间的关系。研究了以下变量:体内喂食和禁食、添加L-乳酸(10 mM)、dl-β-羟基丁酸(10 mM)、胰高血糖素(0.01和1微克/毫升)以及在体外缺血前进行15分钟的缺氧灌注。恢复情况以缺血前功率的百分比来评估。发现功能恢复与缺血后糖原含量之间存在良好的相关性。缺血前缺氧或胰高血糖素导致的糖原耗竭会损害恢复。所产生的乳酸或乳酸与丙酮酸的比值与恢复之间没有关系。向喂食大鼠的心脏中添加乳酸或β-羟基丁酸会增加糖原和6-磷酸葡萄糖的含量,而添加乳酸(而非β-羟基丁酸)可改善恢复情况。糖原含量与6-磷酸葡萄糖水平之间存在线性关系。总之,氧化代谢的恢复程度和糖原净合成反映了缺血后功能的恢复。结果还表明,柠檬酸循环的回补反应作为缺血后恢复的另一个决定因素发挥了作用。