1 A possible mechanism for the action of the K ATP channel opener diazoxide on the improvement of energy metabolism of ischaemic/reperfused hearts was examined. 2 Isolated, perfused rat hearts were subjected to 40 min ischaemia followed by 60 min reperfusion. Diazoxide at concentrations of 3 to 30 mM was present in the perfusion bu er for the last 15 min of pre-ischaemia. 3 Treatment of the perfused heart with diazoxide enhanced the post-ischaemic recovery of ratepressure product, attenuated the post-ischaemic rise in left ventricular end-diastolic pressure, and suppressed the release of creatine kinase and purine nucleosides and bases from the reperfused heart. Treatment of the heart with diazoxide also restored myocardial ATP and creatine phosphate and attenuated the decrease in mitochondrial oxygen consumption rate after reperfusion. This attenuation was maintained at the end of ischaemia as well as at the end of reperfusion. 4 In another set of experiments, myocardial skinned bundles were incubated for 30 min under hypoxic conditions in the presence and absence of diazoxide, and then the mitochondrial oxygen consumption rate was determined. Hypoxia induced a decrease in the mitochondrial oxygen consumption rate of the skinned bundles to approximately 40% of the pre-hypoxic value. In contrast, treatment of the bundles with 30 mM diazoxide preserved the normal mitochondrial oxygen consumption rate during hypoxia. This e ect was abolished concentration-dependently by the combined treatment with either the K ATP channel blocker glibenclamide or 5-hydroxydecanoate. 5 These results suggest that diazoxide is capable of attenuating ischaemia/reperfusion injury of isolated perfused hearts due to preservation of mitochondrial function during ischaemia.

The results suggest that a decrease in SGs and Dys may play an important role in the pathophysiology of CHF following AMI.

These results suggest that attenuation in calpain-induced degradation of DRP complex is a possible mechanism for the Tra- or Can-mediated improvement of the pathogenesis of CHF following myocardial infarction.

The results suggest that activation of PKC and preservation of mitochondrial function are closely linked with each other in the preconditioned heart, which may lead to the improvement of post-ischemic contractile function.

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