Jpn. J. Pharmacol. 85 (4), 435-442 (2001)

Altered Susceptibility to Ischemia-Reperfusion Injury in Isolated-Perfused Hearts of Short-Term Diabetic Rats Associated With Changes in Non-enzymatic Antioxidants

Kam-Ming Ko*, Duncan H.F. Mak, Michel K.T. Poon and Ho-Yan Yiu

Department of Biochemistry, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, China

*Corresponding author. FAX: +852-2358-1552, E-mail:

Abstract: The effects of short-term (2-week) diabetes on myocardial ischemia-reperfusion (I-R) injury and associated changes in myocardial non-enzymatic antioxidant level were examined. Isolated-perfused hearts prepared from control and diabetic rats were subjected to increasing periods of ischemia and reperfusion, and myocardial I-R injury was assessed by measuring the extent of lactate dehydrogenase (LDH) leakage and contractile force recovery. While a brief period (20 min) of post-ischemic reperfusion caused a smaller extent of LDH leakage, the prolonged period (40 min) of reperfusion produced a greater degree of I-R injury in diabetic hearts, as indicated by the impaired recovery of contractile force. The apparent protection against I-R injury in diabetic hearts during the early phase of post-ischemic reperfusion was associated with increases in myocardial reduced glutathione/ascorbic acid and α-tocopherol levels, with the effect on α-tocopherol being most prominent. Insulin treatment could reverse the diabetes-associated changes in susceptibility to myocardial I-R injury and antioxidant response. The ensemble of results indicates that the myocardium isolated from short-term diabetic rat can produce a beneficial antioxidant response to I-R challenge, which may, in turn, be attributable to the decreased susceptibility to I-R injury observable during the early phase of reperfusion.

Keywords: Diabetes, Myocardial ischemia-reperfusion injury, Glutathione, Ascorbic acid, α-Tocopherol
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