REPERFUSION FOLLOWING MYOCARDIAL-ISCHEMIA ENHANCES INOSITOL PHOSPHATE RELEASE IN THE ISOLATED-PERFUSED RAT-HEART

1. Global myocardial ischaemia (MI) for periods greater than 5 min caused an inhibition of phosphatidylinositol specific phospholipase C (PtdIns-PLC) activity. 2. Two min reperfusion following a 20 min MI period, a time point associated with reperfusion-induced arrhythmias, resulted in an activation of PtdIns-PLC activity, dependent on endogenous noradrenaline and mediated via alpha(1)-adrenoceptors. 3. This 2 min reperfusion response, in contrast to healthy myocardium, resulted in: (i) enhanced PtdIns-PLC activity; (ii) increased sensitivity to endogenous noradrenaline; (iii) rapid increases in inositol(l,4,5) trisphosphate (Ins(1,4,5)P-3); and (iv) PLC hydrolysis primarily of PtdIns(4,5)Pz, such that the majority of InsP isomers derive from Ins(1,4,5)P-3. 4. Together, these data suggest a functional role for Ins(1,4,5)P-3 under post-ischaemic reperfusion conditions, and provide a possible link between alpha(1)-adrenoceptor stimulation of the PtdIns turnover pathway and reperfusion injury.