GLYBURIDE, A K-ATP CHANNEL ANTAGONIST, ATTENUATES THE CARDIOPROTECTIVE EFFECTS OF ISOFLURANE IN STUNNED MYOCARDIUM

This investigation examined the role of myocardial adenosine triphosph ate-regulated potassium (K-ATP) channels in isoflurane-induced enhance ment of myocardial function after reversible tissue injury produced by a 15-min left anterior descending coronary artery occlusion (LAD) and reperfusion. Dogs (n = 14) were chronically instrumented for measurem ent of left ventricular (LV) and aortic blood pressure, cardiac output , coronary blood flow velocity, and subendocardial segment length. Reg ional myocardial contractility was evaluated with preload recruitable work area (PRWA). Isovolumic relaxation was assessed with a time const ant (tau). Hemodynamic variables and LV function were measured in the conscious state, during 2% isoflurane anesthesia for 45 min before and during a 15-min LAD occlusion, and at several intervals after reperfu sion in dogs pretreated with glyburide (0.3 mg/kg, intravenously) or d rug vehicle. LAD occlusion caused regional dyskinesia and increases in tau. Vehicle-pretreated dogs demonstrated full recovery of segment sh ortening by 5 h postreperfusion and recovery of PRWA and tau by 30 min postreperfusion. In contrast, dogs pretreated with glyburide demonstr ated sustained systolic and diastolic dysfunction. Segment shortening recovered to only 70% +/- 5%, PRWA remained depressed at 48% +/- 10%, and tau was prolonged to 116% +/- 5% of control values at 5 h postrepe rfusion. The results indicate that isoflurane enhances recovery of myo cardial contractile function by 5 h postreperfusion, in comparison to previous findings in conscious dogs. These effects are partially block ed by glyburide pretreatment, indicating that K-ATP channel activation by isoflurane may mediate these cardioprotective effects.