ISCHEMIC PRECONDITIONING DURING CORONARY ANGIOPLASTY IS PREVENTED BY GLIBENCLAMIDE, A SELECTIVE ATP-SENSITIVE K+ CHANNEL BLOCKER

Background Brief episodes of ischemia render the heart more resistant to subsequent ischemia; this phenomenon has been called ischemic preco nditioning. In some animal species, myocardial preconditioning appears to be due to activation of ATP-sensitive K+ (K-ATP) channels. The rol e played by K-ATP channels in preconditioning in humans remains unknow n. The aim of this study was to establish whether glibenclamide, a sel ective K,, channel blocker, abolishes the ischemic preconditioning obs erved in humans during coronary angioplasty following repeated balloon inflations. Methods and Results Twenty consecutive patients undergoin g one-vessel coronary angioplasty were randomized to receive 10 mg ora l glibenclamide or placebo. Sixty minutes after glibenclamide or place bo administration, patients were given an infusion of 10% dextrose (8 ml/min) to correct glucose plasma levels or, respectively, an infusion of saline at the same infusion rate. Thirty minutes after the beginni ng of the infusion, both patient groups underwent coronary angioplasty . The mean values (+/-1 SD) of ST-segment shifts on the surface 12-lea d ECG and the intracoronary ECG were measured at the end of the first and second balloon inflations, both 2 minutes long. In glibenclamide-t reated patients, the mean ST-segment shift during the second balloon i nflation was similar to that observed during the first inflation (23+/ -13 versus 20+/-8 mm, P=NS), and the severity of cardiac pain was grea ter (55+/-21 versus 43+/-23 mm on a scale of 0 to 100, P<.05). Convers ely, in placebo-treated patients the mean ST-segment shift during the second inflation was less than that during the first inflation (9+/-5 versus 23+/-13 mm, P<.001), as was the severity of cardiac pain (15+/- 15 versus 42+/-19 mm, P<.01). Blood glucose levels were significantly reduced 60 minutes after glibenclamide compared with those at baseline (53+/-9 versus 102+/-10 mg/100 mL, P<.001) in the glibenclamide group ; however, before coronary angioplasty, blood glucose levels increased to 95+/-19 mg/100 mL, a value similar to that found in placebo group (96+/-11 mg/100 mL, P=NS). Conclusions In humans, ischemic preconditio ning during brief repeated coronary occlusions is completely abolished by pretreatment with glibenclamide, thus suggesting that it is mainly mediated by K-ATP channels.