ROLE OF MYOCARDIAL ATP-SENSITIVE POTASSIUM CHANNELS IN MEDIATING PRECONDITIONING IN THE DOG HEART AND THEIR POSSIBLE INTERACTION WITH ADENOSINE-A(1)-RECEPTORS

Background. A brief period of myocardial ischemia can result in an increased resistance to subsequent, more severe episodes of ischemia. Recent studies have indicated that activation of adenosine A1-receptors may mediate this preconditioning effect. It is also known that A1-activation can lead to ATP-sensitive potassium channel (K(ATP)) opening via a G(i) protein-mediated effect. Thus, we determined whether the K(ATP) blocker glyburide could abolish preconditioning or the protective effects of A1-receptor activation. Methods and Results. Anesthetized dogs were subjected to 5 minutes of left circumflex coronary artery (LCx) occlusion (or sham) followed by 10 minutes of reperfusion. The hearts were then subjected to 60 minutes of LCx occlusion and 5 hours of reperfusion. Glyburide (5 mug/kg/min) or vehicle was given directly into the LCx 20 minutes before preconditioning or sham preconditioning. Preconditioning resulted in a significantly reduced infarct size compared with nonpreconditioned animals. Glyburide abolished the protective effect of preconditioning. To establish a link between K(ATP) and A1-receptor activation, the effect of the A1-agonist R-PIA with or without glyburide on infarct size was determined. R-PIA (0.4 mug/kg/min, directly into the LCx) significantly reduced infarct size, and this protective effect was abolished by glyburide. None of the treatments described above had a significant effect on peripheral hemodynamic status or myocardial blood How. Conclusions. Preconditioning may be mediated by K(ATP) activation, and this may be linked to A1-receptor stimulation.