Sargent C A, Dzwonczyk S, Sleph P, Wilde M, Grover G J
Department of Cardiovascular Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Am J Physiol. 1994 Oct;267(4 Pt 2):H1403-9. doi: 10.1152/ajpheart.1994.267.4.H1403.
Isolated rat hearts can be protected by preconditioning, although this has not been found when they are perfused with pyruvate. We addressed the question of whether pyruvate could increase the threshold for preconditioning in isolated rat hearts and whether this could be overcome with increased durations of ischemia. A protocol of four periods of 5 min of ischemic preconditioning (4 x 5 min) protected hearts (improved recovery of function, reduced lactate dehydrogenase release) not perfused with pyruvate from a subsequent 30-min period of global ischemia, but did not protect pyruvate-perfused hearts. Pilot studies indicated that hearts perfused in the presence of pyruvate must be ischemic for approximately 40% longer to produce equivalent ischemic damage in nonpyruvate-treated hearts. Thus the preconditioning period of 5 min was increased by approximately 40% to 7 min to produce equivalent degrees of preconditioning. Hearts preconditioned with the 4 x 7 min protocol with pyruvate were significantly protected against a subsequent severe global ischemia (enhanced recovery of function, reduced lactate dehydrogenase release). High-energy phosphates were measured at the end of the preconditioning protocol (before final global ischemia) to determine whether there was a correlation between cardioprotection and high-energy phosphate levels. There was no correlation between ATP, ADP, or AMP levels and the efficacy of preconditioning. However, an increase in creatine phosphate was associated with cardioprotection, although the importance of this in mediating preconditioning is doubtful. Thus the ability to precondition rat hearts is somewhat dependent on their energy source, but this appears to be due to changes in the severity of the ischemic preconditioning event.
孤立的大鼠心脏可通过预处理得到保护，尽管在用丙酮酸灌注时未发现这种情况。我们探讨了丙酮酸是否能提高孤立大鼠心脏预处理的阈值，以及这是否能通过延长缺血时间来克服。一个由四个5分钟缺血预处理期（4×5分钟）组成的方案可保护未用丙酮酸灌注的心脏（改善功能恢复，减少乳酸脱氢酶释放）免受随后30分钟全心缺血的影响，但不能保护用丙酮酸灌注的心脏。初步研究表明，在丙酮酸存在下灌注的心脏必须缺血约40%更长时间，才能在未用丙酮酸处理的心脏中产生等效的缺血损伤。因此，将5分钟的预处理期增加约40%至7分钟，以产生等效程度的预处理。用4×7分钟方案进行丙酮酸预处理的心脏在随后的严重全心缺血中得到了显著保护（功能恢复增强，乳酸脱氢酶释放减少）。在预处理方案结束时（在最终全心缺血之前）测量高能磷酸盐，以确定心脏保护与高能磷酸盐水平之间是否存在相关性。ATP、ADP或AMP水平与预处理效果之间没有相关性。然而，磷酸肌酸的增加与心脏保护有关，尽管其在介导预处理中的重要性值得怀疑。因此，对大鼠心脏进行预处理的能力在一定程度上取决于其能量来源，但这似乎是由于缺血预处理事件严重程度的变化所致。
