Doenst T, Guthrie P H, Chemnitius J M, Zech R, Taegtmeyer H
Department of Internal Medicine, University of Texas Houston Medical School 77030, USA.
Am J Physiol. 1996 May;270(5 Pt 2):H1607-15. doi: 10.1152/ajpheart.1996.270.5.H1607.
We tested the hypothesis that improved ischemia tolerance in an isolated working rat heart preparation can be achieved by interventions other than ischemic preconditioning. Hearts were perfused at near-physiological workload with bicarbonate buffer containing glucose (10 mM). A preischemic period of 25 min was followed by 15 min of global ischemia and 30 min of reperfusion under preischemic conditions. Hearts came from either fed or fasted animals (groups 1 and 2). In group 3 lactate (10 mM) and insulin (10 mU/ml) were added to the perfusate of fasted animals. In group 4 hearts from fed animals were perfused with glucose (10 mM) and were ischemically preconditioned by one cycle of ischemia between 10 and 15 min of the preischemic perfusion. Cardiac power and glucose uptake were measured continuously to assess functional and metabolic recovery. In addition, we measured the time to return of aortic flow. Glucose metabolites and the ratio of latent of free citrate synthase activity (citrate synthase ratio, a marker for the structural integrity of mitochondria) were determined at selected time points. Groups 2, 3, and 4 recovered significantly faster than group 1, whereas recovery of power showed an improvement in groups 3 and 4 only. In addition, there was an early increase in glucose uptake during reperfusion in these two groups, suggesting an early need for glucose substrate. Glycogen levels decreased with ischemia in all groups and returned to preischemic levels in groups 2, 3, and 4. The citrate synthase ratio was low in the control group and preserved in the groups showing improved functional recovery. We conclude that metabolic interventions may be as effective as ischemic preconditioning in protecting the heart from ischemic injury.
在离体工作大鼠心脏标本中，除缺血预处理外，通过其他干预措施也可实现缺血耐受性的提高。心脏在接近生理负荷下用含葡萄糖（10 mM）的碳酸氢盐缓冲液灌注。在缺血预处理25分钟后，进行15分钟的全心缺血和30分钟的缺血预处理条件下的再灌注。心脏取自喂食或禁食的动物（第1组和第2组）。在第3组中，向禁食动物的灌注液中添加乳酸（10 mM）和胰岛素（10 mU/ml）。在第4组中，用葡萄糖（10 mM）灌注来自喂食动物的心脏，并在缺血预处理灌注的10至15分钟之间通过一个缺血周期进行缺血预处理。连续测量心脏功率和葡萄糖摄取以评估功能和代谢恢复。此外，我们测量了主动脉血流恢复的时间。在选定的时间点测定葡萄糖代谢产物和游离柠檬酸合酶活性潜伏期的比值（柠檬酸合酶比值，线粒体结构完整性的标志物）。第2、3和4组的恢复明显快于第1组，而功率恢复仅在第3和4组有所改善。此外，这两组在再灌注期间葡萄糖摄取早期增加，表明早期需要葡萄糖底物。所有组的糖原水平随缺血而降低，第2、3和4组恢复到缺血前水平。对照组的柠檬酸合酶比值较低，而在功能恢复改善的组中保持不变。我们得出结论，代谢干预在保护心脏免受缺血性损伤方面可能与缺血预处理一样有效。
