ABSTRACT
This study aimed to examine the effects of three different sulfonylureas: Glibenclamide, glicazide and glimepiride, on the warm-up phenomenon by analyzing the results of 2 consecutive exercise tests in diabetic patients with coronary artery disease [CAD]. In subjects with CAD, the angina induced by initial exercise is attenuated with re-exercise after a brief test. This warm-up phenomenon believed to be due to ischemic preconditioning is related to the opening of cardiac ATP-sensitive K channels [K [ATP]]. Blockers of these K[ATP] channels such as the sulphonylurea drugs, can lead to loss of ischemic preconditioning. Forty patients with chronic stable angina: 30 patients having type 2 diabetes mellitus [DM] and 10 non diabetic patients [group D] were enrolled in the study. The DM patients were divided into 3 groups according to the type of sulfonylurea drug they are receiving: Group A [glibenclamide] Group B [gliclazide] and group C [glimepiride]. All patients were subjected to 2 consecutive exercise tests with a 15-minute recovery period between the 2 tests. There was a non significant increase in peak heart rate, systolic blood pressure and rate pressure product during test 2 compared to test 1 in groups B, C and D but not in group A patients. There was a statistically significant increase in the time to onset of typical chest pain [p<0.007 for B, C and <0.005 for D], time to onset of 1mm ST segment depression [p<0.007 for B, C and <0.03 for D] and exercise duration [p<0.01 for B; p<0.08 for C and p<0.02 for D] in test 2 compared to test 1 in groups B, C and D but not in group A patients. There was also a statistically significant decrease in time to ST segment recovery to baseline in test 2 compared to test 1 in groups B, C and D [p<0.005 in the 3 groups] but not in group A patients. Glibenclamide, but not gliclazide or glimepiride abolished the warm-up phenomenon, the clinical counterpart of ischemic preconditioning in type II DM patients with CAD