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.

*Contracture, *Ischemic Preconditioning, Myocardial, Animals, Heart/*physiopathology, Male, Myocardial Ischemia, Myocardial Reperfusion Injury/metabolism/*physiopathology, Myocardium/*metabolism, Rats, Wistar, rats
Journal of Molecular and Cellular Cardiology
Erasmus MC: University Medical Center Rotterdam

Arad, M, de Jong, J.W, de Jonge, R, Huizer, T, & Rabinowitz, B. (1996). Preconditioning in globally ischemic isolated rat hearts: effect on function and metabolic indices of myocardial damage. Journal of Molecular and Cellular Cardiology. Retrieved from http://hdl.handle.net/1765/8911