Preconditioning of perfused rat heart inhibits reperfusion-induced release of inositol(1,4,5)trisphosphate.

Preconditioning the heart by brief episodes of ischemia and reperfusion can be cardioprotective to injury from subsequent sustained ischemia and reperfusion. Such protective effects include the reduction of reperfusion-induced arrhythmias. We have previously reported a rapid rise in the second messenger inositol(1,4,5) trisphosphate with post-ischemic reperfusion, which has been implicated in the generation of reperfusion-induced arrhythmia. Given the possible importance of inositol(1,4,5)trisphosphate, studies were performed in isolated perfused rat hearts to determine if preconditioning could reduce the reperfusion-induced rise in inositol(1,4,5) trisphosphate. [3H]Inositol labeled hearts underwent 20 min global ischemia with or without 2 min reperfusion. This was preceded by preconditioning of two or three cycles of 2 or 5 min ischemia separated by 5 or 10 min reperfusion, or by time matched control perfusions. Two min reperfusion following 20 min ischemia in time matched controls caused an increase of [3H]inositol(1,4,5)trisphosphate from 20 +/- 3 cpm/mg protein to 52 +/- 5 cpm/mg protein (mean +/- S.E.M. n = 4, P < 0.01). Preconditioning of three cycles of 5 min ischemia and 5 min reperfusion inhibited the 2 min reperfusion-induced rise in [3H]inositol(1,4,5)trisphosphate (26 +/- 4 cpm/mg protein. P < 0.01 relative to non-preconditioned hearts), however protocols that involved either fewer ischemic cycles or shorter ischemic periods were ineffective. Preconditioning did not affect myocardial ATP levels or norepinephrine release with sustained ischemia and reperfusion. Inhibition of the reperfusion-induced rise in inositol(1,4,5) trisphosphate may provide an explanation for the inhibitory effects of preconditioning on reperfusion-induced arrhythmias.