Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+ channel blocker

Abstract

Background: Brief episodes of ischemia render the heart more resistant to subsequent ischemia; this phenomenon has been called ischemic preconditioning. In some animal species, myocardial preconditioning appears to be due to activation of ATP-sensitive K+ (K(ATP)) channels. The role played by K(ATP) channels in preconditioning in human remains unknown. The aim of this study was to establish whether glibenclamide, a selective K(ATP) channel blocker, abolishes the ischemic preconditioning observed in humans during coronary angioplasty following repeated balloon inflations. Methods and Results: Twenty consecutive patients undergoing one-vessel coronary angioplasty were randomized to receive 10 mg oral glibenclamide or placebo. Sixty minutes after glibenclamide or placebo 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 beginning of the infusion, both patient groups underwent coronary angioplasty. The mean values (±1 SD) of ST-segment shifts on the surface 12-lead ECG and the intracoronary ECG were measured at the end of the first and second balloon inflations, both 2 minutes long. In glibenclamide- treated patients, the mean ST-segment shift during the second balloon inflation was similar to that observed during the first inflation (23±13 versus 20±8 mm, P=NS), and the severity of cardiac pain was greater (55±21 versus 43±23 mm on a scale of 0 to 100, P