Acute diabetes modulates response to ischemia in isolated rat heart

Diabetic hearts are suggested to exhibit either increased or lower sensitiv ity to ischemia. Detrimental effects of prolonged ischemia can be attenuate d by preconditioning, however, relatively little is known about its effects in the diseased myocardium. This study was designed to test the susceptibi lity to ischemia-induced arrhythmias and the effect of preconditioning in t he diabetic heart. Rats were made diabetic with streptozotocin (45 mg/kg, i .v.). After 1 week, isolated Langendorff-perfused hearts were subjected to 30 min occlusion of LAD coronary artery without or with preceding precondit ioning induced by one cycle of 5 min ischemia and 10 min reperfusion. Glyco gen and lactate contents were estimated in the preconditioned and non-preco nditioned hearts before and after ischemia. Diabetic hearts were more resis tant to ischemia-induced arrhythmias: incidence of ventricular tachycardia (VT) decreased to 42% and only transient ventricular fibrillation (VF) occu rred in 17% of the hearts as compared to the non-diabetic controls (VT 100% and VF 70% including sustained VF 36%; p < 0.05). Preconditioning effectiv ely suppressed the incidence and severity of arrhythmias (VT 33%, VF 0%) in the normal hearts. However, this intervention did not confer any additiona l protection in the diabetic hearts. Despite higher glycogen content in the diabetic myocardium and greater glycogenolysis during ischemia, production of lactate in these hearts was significantly lower than in the controls. P reconditioning caused a substantial decrease in the accumulation of lactate in the normal hearts, whereby in the diabetic hearts, this intervention di d not cause any further reduction in the level of lactate. In conclusion, d iabetic rat hearts exhibit lower susceptibility to ischemic injury and show no additional response to preconditioning. Reduced production of glycolyti c metabolites during ischemia can account for the enhanced resistance of di abetic hearts to ischemia as well as for the lack of further protection by preconditioning.