The Cardioprotection By NHEI To Diabetic Rat Hearts Is Inhibited By Sulphonylurea

Objectives: To investigate if amiloride, a Na~+-H~+ exchange inhibitor, can protect the isolated diabetic rat hearts against ischemia reperfusion injury, and to observe the effect of glibenclamide on the role of amiloride. Methods: 40 Sprague-Dawley(SD) rats were randomizedly divided into five groups, ie Nc group, Dm group, Ami group, Gli group, A+G group. The latter four groups were diabetic groups. After being fed for 4 weeks, all rats' hearts were isolated for perfusing with oxygenated K-H solution and underwent 20-min global ischemia and 30-min reperfusion. The Ami and Gli group received 0.1mmol/l amiloride and 10μmol/l glibenclamide 15-min before ischemia and 10-min after reperfusion respectively, the A+G group received the same doses of amiloride and glibenclamide, the Nc and Dm group received only DMSO solvent. LVSP and LVEDP and HR and CF were recorded before ischemia and at the end of reperfusion. LVDP and the recovery degrees of HR and CF and LVDP were calculated. At the end of reperfusion, coronary effluent was collected for measuring myocardial enzymes include CK and LDH.Results: Before ischemia, diabetic groups had obvious lower LVSP and LVDP than Nc group (P<0.05), there were no significant differences in LVEDP among all groups(P=0.075). At the end of reperfusion, CF and CF recoverydegrees and LVDP recovery degrees in diabetic groups were significantly higher than Nc group, CK and LDH in diabetic groups were lower than Nc group(P<0.05). there were no significant intergroup differences in HR and HR recovery degree among all groups. Compared with other diabetic groups, Ami group had higher LVDP recovery degree(P<0.05), although LVDP recovery degree of A+G group was higher than Dm and Gli groups, there were no significant intergroup diffences among them(P=0.07). CK and LDH of Ami group were sifhificantly lower than Dm and Gli groups(P<0.05). CK of Ami group was also sifnificantly lower than A+G group, but LDH of Ami group was slightly lower than A+G group(P=0.132). There were no significant intergroup differences in CK and LDH among Dm, Gli and A+G groups. Conclusions: Diabetic myocardium is less sensitive to ischemia and reperfusion injury than non-diabetic myocardium. Amiloride can protect diabetic myocardium against ischemia and reperfusion injury, glibenclamide may block the protection of amiloride.