Abstract

BackgroundSensitivity to ischemia and its underlying mechanisms in type 2 diabetic hearts are still largely unknown. Especially, correlation between reperfusion induced ventricular arrhythmia and changes in intracellular pH has not been elucidated.Methods and resultsMale Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 16 and 32 weeks of age were used along with age-matched nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. Hearts from rats in these 4 groups were perfused in the working heart mode, thus inducing whole heart ischemia. At 16 weeks of age, no differences in blood glucose levels or incidence and duration of reperfusion arrhythmia were found between the strains. At 32 weeks of age, both impaired glucose tolerance and obesity were observed in the OLETF rats. Further, the duration of reperfusion-induced ventricular fibrillation (VF) was significantly longer in the OLETF rats, while the pH level was significantly lower and proton contents were significantly higher in coronary effluent during ischemia in those rats. Following treatment with troglitazone, improvements in pH and proton level in coronary effluent during ischemia were observed, as was the duration of reperfusion-induced VF in OLETF rats at 32 weeks of age.ConclusionThe hearts of spontaneously diabetic OLETF rats were found to be more susceptible to ischemic insult. Troglitazone treatment improved ischemic tolerance by improving glucose metabolism in the myocardium of those rats.

Highlights

  • Sensitivity to ischemia and its underlying mechanisms in type 2 diabetic hearts are still largely unknown

  • The hearts of spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats were found to be more susceptible to ischemic insult

  • A prolonged duration of reperfusion arrhythmia was observed in hearts from OLETF rats at 32 weeks of age, in which obesity and hyperglycemia were confirmed by oral glucose tolerance test (OGTT) results

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Summary

Introduction

Sensitivity to ischemia and its underlying mechanisms in type 2 diabetic hearts are still largely unknown. Correlation between reperfusion induced ventricular arrhythmia and changes in intracellular pH has not been elucidated. To elucidate the mechanisms of these actions, recently, echocardiographical study [3] or some whole heart perfusion experiments using type 2 diabetic model rodents have been performed. Alterations in energy metabolism in the myocardium of type 2 diabetic rodents have been well investigated [4,5,6], whereas ion homeostasis has been rarely investigated [7] in ischemia-reperfusion study. We induced ischemia in perfused OLETF rat hearts in order to examine the changes in pH and proton production, during and after ischemia, as well as the incidence and duration of ventricular arrhythmia after reperfusion. We observed if improvement in diabetic state by troglitazone [9], a thiazolidinedione, acts to the ischemic injury in heart from diabetic OLETF rat

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