THE EVOLUTION OF DIABETIC RESPONSE TO ISCHEMIA REPERFUSISN AND PRECONDITIONING IN ISOLATED WORKING RAT HEARTS/

Objective: Studies have shown that the diabetic heart exhibits abnorma lities in cellular ion transport, which can affect susceptibility to r eperfusion-induced ventricular fibrillation (VF), tachycardia (VT) and functional derangements. It has been shown that ''preconditioning'' r enders the heart very resistant to a subsequent prolonged ischemic epi sode. This phenomenon has been extensively studied in healthy myocardi um, but such a study has not been previously done in diseased (hypertr ophic or myopathic) hearts. Methods: We studied the incidence of reper fusion-induced VF, VT, cardiac function, and ion shifts (Na+, K+, Ca2, and Mg2+) induced by ischemia/reperfusion in isolated hearts from ra ts with streptozotocin-induced diabetes. Following 2, 4, 6, and 8 week s of diabetes, hearts were isolated and subjected to 30 min global isc hemia followed by reperfusion. Results: In the 2-week diabetic group t he total incidence of VF and VT was reduced from their non-diabetic ag e-matched control. value of 100 and 100% to 42 (P < 0.05) and 42% (P < 0.05), respectively. Such a reduction in the incidence of VF and VT w as not observed with progressive diabetes (4, 6, and 8 weeks). In the 2-week diabetics, the reduction in the VF and VT was reflected in the improvement of postischemic function, the reduction of ischemia and re perfusion-induced Na+ and Ca2+ gains, and the prevention in K+ and Mg2 + loss. This diabetes-induced initial protection was not seen in the 4 - and 6-week diabetics, and a deterioration of postischemic function w as observed in the 8-week diabetics. Four cycles of preconditioning, e ach consisting of 5 min ischemia followed by 10 min reperfusion, faile d to reduce the incidence of VF and VT, improve cardiac function, and prevent ion shifts induced by 30 min ischemia followed by 30 min reper fusion in 4- and X-week diabetics. Conclusions: In the early phase of diabetes the heart is more resistant to ischemia/reperfusion than the non-diabetic heart. Preconditioning does not afford protection against a prolonged period of ischemia in diabetics, indicating that precondi tioning may be 3. ''healthy heart phenomenon''.