Diabetic hearts are suggested to exhibit either increased or lower sensitivity to ischemia. Detrimental effects of prolonged ischemia can be attenuated by preconditioning, however, relatively little is known about its effects in the diseased myocardium. This study was designed to test the susceptibility to ischemia-induced arrhythmias and the effect of preconditioning in the 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 preconditioning induced by one cycle of 5 min ischemia and 10 min reperfusion. Glycogen and lactate contents were estimated in the preconditioned and non-preconditioned hearts before and after ischemia. Diabetic hearts were more resistant to ischemia-induced arrhythmias: incidence of ventricular tachycardia (VT) decreased to 42% and only transient ventricular fibrillation (VF) occurred 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="" effectively="" suppressed="" the="" incidence="" and="" severity="" of="" arrhythmias="" (vt="" 33%,="" vf="" 0%)="" in="" the="" normal="" hearts.="" however,="" this="" intervention="" did="" not="" confer="" any="" additional="" 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.="" preconditioning="" caused="" a="" substantial="" decrease="" in="" the="" accumulation="" of="" lactate="" in="" the="" normal="" hearts,="" whereby="" in="" the="" diabetic="" hearts,="" this="" intervention="" did="" not="" cause="" any="" further="" reduction="" in="" the="" level="" of="" lactate.="" in="" conclusion,="" diabetic="" rat="" hearts="" exhibit="" lower="" susceptibility="" to="" ischemic="" injury="" and="" show="" no="" additional="" response="" to="" preconditioning.="" reduced="" production="" of="" glycolytic="" metabolites="" during="" ischemia="" can="" account="" for="" the="" enhanced="" resistance="" of="" diabetic="" hearts="" to="" ischemia="" as="" well="" as="" for="" the="" lack="" of="" further="" protection="" by="">