0061 : Exercice training impaired energy metabolism and function of the type 2 diabetic Goto-Kakizaki (GK) rat heart during ischaemiareperfusion injury

Abstract

Informations about the effects of exercice training on diabetesinduced myocardial dysfunctions are lacking. Consequently, we investigated the effect of exercice training on the sensitivity of the type 2 diabetic Goto-Kakizaki (GK) rat heart to ischaemia-reperfusion injury by using a multiparametric approach combining 31P magnetic resonance spectroscopy (MRS) with simultaneous measurement of contractile function and biochemical assays. 8-month-old male GK rat (n=11, trained GK) rats ran 60 min on a treadmill 5 days/week at a speed of 20 m/min for 7 weeks and compared with age-matched male Control (n=6) and untrained GK (n=11) rats. Then, isolated rat hearts were perfused with a physiological buffer containing 0.4 mM palmitate, for 24 min before switching to 1.2mM palmitate during 32min low-flow (0.5 ml/min-1.g wet wt-1) ischaemia. Next, flow was restored with 0.4 mM palmitate buffer for 32 minutes. High energy compounds and intracellular pH were followed using 31P MRS with simultaneous measurement of contractile function. Total adenine nucleotides (TAN) and energy charge (EC) were determined in freeze-clamped tissues by H.P.L.C. Heart to body weight ratios were significantly higher in both untrained and trained diabetic groups (p<0.02) versus Control. During reperfusion, rate pressure product and recoveries of PCr and ATP were significantly lower (p<0.05) in trained GK versus untrained GK and Control rat hearts. TAN and EC were significantly decreased in trained GK compared with Control (p=0.0052 and p=0.0156) and untrained GK (p=0.0024 and p=0.0005) rat hearts. The intensity of exercice training exacerbed the sensitivity of the type 2 diabetic 8-month-old Goto-Kakizaki rat to myocardial ischaemiareperfusion by impairing energy metabolism and myocardial performance. Other exercice protocols and/or therapeutic approaches need to be explored to limit myocardial ischaemia-reperfusion injury in type 2 diabetes.