Arad M, de Jong J W, de Jonge R, Huizer T, Rabinowitz B
Heart Institute, Sheba Medical Center, Tel Hashomer, Israel.
J Mol Cell Cardiol. 1996 Dec;28(12):2479-90. doi: 10.1006/jmcc.1996.0240.
We assessed the effects of ischemic preconditioning on heart recovery and metabolic indices of damage following global ischemia and reperfusion, in relationship to post-ischemic lactate release. Three groups of Langendorff rat hearts were studied: (1) A control group of 40 min global ischemia and 45 min reperfusion; (2) preconditioning by 5 min global ischemia and 15 min reperfusion prior to sustained ischemia and reperfusion; (3) Preconditioning by three episodes of brief ischemia-reperfusion prior to sustained ischemia. Repetitive episodes of brief ischemia-reperfusion were associated with increased reactive hyperemia, decreased release of purines and prostaglandin 6-keto F1 alpha, lower tissue glycogen but no change in lactate washout. After 40 min ischemia, release of lactate was 173 +/- 17, 196 +/- 6 and 149 +/- 9 mumol/g in groups 1, 2 and 3, respectively (P < 0.01, group 2 v group 3). Preconditioning had no effect on ischemic arrest but had divergent effects on the development and the magnitude of ischemic contracture: delay and attenuation in group 2 but enhanced onset in group 3. Preconditioning provided a dose-dependent protection from the increase in left ventricular end-diastolic pressure, reduced the reperfusion release of purine metabolites and of creatine kinase, but neither improved systolic function nor prevented arrhythmia. 6-Keto F1 alpha production was 87 +/- 13, 132 +/- 19 and 241 +/- 35 pmol/g in groups 1, 2, 3, respectively (P < 0.01 group 1 v group 3). We conclude that when subjected to prolonged global ischemia, preconditioned isolated rat hearts develop less post-ischemic contracture, lose less purine nucleosides and creatine kinase activity. In addition, preconditioning leads to increased production of prostacyclin. Differences among preconditioning protocols in lactate production seem to be related to the ischemic contracture development, but may not play an ultimate role in attenuation of myocardial damage or improvement of postischemic recovery.
我们评估了缺血预处理对全心缺血及再灌注后心脏恢复和损伤代谢指标的影响，并研究其与缺血后乳酸释放的关系。研究了三组采用Langendorff装置的大鼠心脏：（1）对照组，全心缺血40分钟，再灌注45分钟；（2）在持续缺血和再灌注之前，先进行5分钟全心缺血和15分钟再灌注的预处理；（3）在持续缺血之前，进行三次短暂缺血-再灌注的预处理。重复性短暂缺血-再灌注与反应性充血增加、嘌呤和前列腺素6-酮-F1α释放减少、组织糖原降低有关，但乳酸清除无变化。缺血40分钟后，第1、2和3组的乳酸释放量分别为173±17、196±6和149±9μmol/g（P<0.01，第2组与第3组比较）。预处理对缺血停搏无影响，但对缺血性挛缩的发生和程度有不同影响：第2组延迟且减轻，而第3组发作增强。预处理对左心室舒张末期压力升高具有剂量依赖性保护作用，减少了嘌呤代谢产物和肌酸激酶的再灌注释放，但既未改善收缩功能，也未预防心律失常。第1、2、3组的6-酮-F1α生成量分别为87±13、132±19和241±35pmol/g（P<0.01，第1组与第3组比较）。我们得出结论，当经历长时间全心缺血时，预处理的离体大鼠心脏缺血后挛缩减轻，嘌呤核苷和肌酸激酶活性丧失减少。此外，预处理导致前列环素生成增加。预处理方案在乳酸生成方面的差异似乎与缺血性挛缩的发生有关，但可能在减轻心肌损伤或改善缺血后恢复方面不起最终作用。
