Streptozotocin-induced type II diabetic rat administered with nonobesogenic high-fat diet is highly susceptible to myocardial ischemia-reperfusion injury: An insight into the function of mitochondria.

RATIONALE: Our recent study suggested that ischemia-reperfusion (I/R) induced oxidative stress was minimal in the rat heart during initial stage of diabetes and the one that progressed to diabetic cardiomyopathy (DCM), despite having higher infarct and low cardiac performance. Mitochondrial dysfunction is an important mediator for adverse outcome in rat heart affected with diabetes, which is also a potential contributor for the cardiac reperfusion injury.

OBJECTIVE

The current study aims to evaluate the susceptibility of diabetes heart with or without myopathy to I/R injury and its influence on cardiac mitochondrial function.

METHODS AND

RESULTS

Male Wistar rats (3 weeks old) were fed with high-fat diet for 8 weeks followed by diabetes mellitus (DM) induction via streptozotocin (35 mg/kg body weight) and maintained for further 4 weeks. The animal displayed cardiomyopathy characteristics like hypertrophy, fibrosis, and insulin resistance-termed diabetic cardiomyopathy (DCM). To study the specific effect of DCM on I/R, we included diabetic rats without cardiomyopathy. Induction of I/R in different groups suggested higher vulnerability to injury in DCM rat hearts than DM and normal (measured via hemodynamics, triphenyltetrazolium chloride stain, and apoptotic markers). Mitochondrial function at the subpopulation level was evaluated with respect to adenosine triphosphate (ATP) concentration, membrane potential, swelling behavior, and oxidative stress, wherein the results confirmed I/R-induced mitochondrial dysfunction. Unlike normal heart, DM, and DCM heart challenged to I/R exhibited altered ATP producing capacity among subsarcolemmal and interfibrillar mitochondria.

CONCLUSION

The above results suggest that mitochondrial changes associated with diabetes and cardiomyopathy significantly contribute to the adverse outcome of I/R injury.