K Ovünç1. 1. Hacettepe University, Faculty of Medicine, Department of Cardiology, Ankara, Turkey.
Abstract
BACKGROUND: Warm-up phenomenon, one of the clinical models of ischemic preconditioning, refers to an increased tolerance to myocardial ischemia during the second of two consecutive exercise tests. HYPOTHESIS: Blockers of K(ATP) channels, such as the sulfonylurea drugs, can induce loss of ischemic preconditioning. This study aimed to investigate the effects of glibenclamide, a sulfonylurea with a high affinity for myocardial K(ATP) channels, on the results of two consecutive exercise tests in diabetic patients with coronary artery disease. METHODS: Eighteen type II diabetic patients with chronic stable angina pectoris participated in this study. All patients underwent two consecutive treadmill exercise tests with a recovery period of 15 min in fasting state. On the day after these exercise tests, 10 mg oral glibenclamide was given to the same patients and 30 min later 200 ml of 30% glucose solution was given orally. Half an hour later, which is the time of peak plasma levels of glibenclamide, two exercise tests were repeated consecutively with a 15 min recovery period. RESULTS: There was no difference in blood glucose levels before and after exercise tests on each day (p > 0.05). Without glibenclamide, heart rate, rate-pressure product at 1.5 mm ST depression, and peak exercise increased significantly (p < 0.05). Time to 1.5 mm ST-segment depression and onset of pain, as well as duration of exercise also increased, but ST-segment depression and ST-recovery time significantly decreased (p < 0.05). In contrast, these values did not significantly change after glibenclamide (p>0.05), with a significant drug-test interaction (p < 0.05, at two-way ANOVA). CONCLUSIONS: Glibenclamide, an oral hypoglycemic agent with a K(ATP) channel-blocker activity, with a 10 mg oral dose, abolished the warm-up phenomenon which is a clinical finding of ischemic preconditioning on two consecutive exercise tests. Therefore, glibenclamide should be used carefully in patients with coronary heart disease and diabetes mellitus since this agent leads to a decrease in ischemic threshold and exercise capacity.
BACKGROUND: Warm-up phenomenon, one of the clinical models of ischemic preconditioning, refers to an increased tolerance to myocardial ischemia during the second of two consecutive exercise tests. HYPOTHESIS: Blockers of K(ATP) channels, such as the sulfonylurea drugs, can induce loss of ischemic preconditioning. This study aimed to investigate the effects of glibenclamide, a sulfonylurea with a high affinity for myocardial K(ATP) channels, on the results of two consecutive exercise tests in diabeticpatients with coronary artery disease. METHODS: Eighteen type II diabeticpatients with chronic stable angina pectoris participated in this study. All patients underwent two consecutive treadmill exercise tests with a recovery period of 15 min in fasting state. On the day after these exercise tests, 10 mg oral glibenclamide was given to the same patients and 30 min later 200 ml of 30% glucose solution was given orally. Half an hour later, which is the time of peak plasma levels of glibenclamide, two exercise tests were repeated consecutively with a 15 min recovery period. RESULTS: There was no difference in blood glucose levels before and after exercise tests on each day (p > 0.05). Without glibenclamide, heart rate, rate-pressure product at 1.5 mm ST depression, and peak exercise increased significantly (p < 0.05). Time to 1.5 mm ST-segment depression and onset of pain, as well as duration of exercise also increased, but ST-segment depression and ST-recovery time significantly decreased (p < 0.05). In contrast, these values did not significantly change after glibenclamide (p>0.05), with a significant drug-test interaction (p < 0.05, at two-way ANOVA). CONCLUSIONS:Glibenclamide, an oral hypoglycemic agent with a K(ATP) channel-blocker activity, with a 10 mg oral dose, abolished the warm-up phenomenon which is a clinical finding of ischemic preconditioning on two consecutive exercise tests. Therefore, glibenclamide should be used carefully in patients with coronary heart disease and diabetes mellitus since this agent leads to a decrease in ischemic threshold and exercise capacity.
Authors: Leonid V Zingman; Denice M Hodgson; Peter H Bast; Garvan C Kane; Carmen Perez-Terzic; Richard J Gumina; Darko Pucar; Martin Bienengraeber; Petras P Dzeja; Takashi Miki; Susumu Seino; Alexey E Alekseev; Andre Terzic Journal: Proc Natl Acad Sci U S A Date: 2002-09-23 Impact factor: 11.205