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.