ATP-SENSITIVE POTASSIUM CHANNEL ACTIVATION BEFORE CARDIOPLEGIA - EFFECTS ON VENTRICULAR AND MYOCYTE FUNCTION

Background-Pretreatment with potassium channel openers (PCOs) has been shown to provide protective effects in the setting of myocardial isch emia. The goal of the present study was to examine whether PCO pretrea tment would provide protective effects on left ventricular (LV) and my ocyte function after cardioplegic arrest, Methods and Results-The firs t study quantified the effects of PCO pretreatment on LV myocyte contr actility after simulated cardioplegic arrest. LV porcine myocytes were randomly assigned to 3 groups: (1) normothermic control: 37 degrees C x2 hours (n=116); (2) cardioplegia: K+ 24 mEq/L, 4 degrees Cx2 hours f ollowed by reperfusion and rewarming (n=62); and (3) PCO/cardioplegla: 5 minutes of PCO treatment (50 mu mol/L, SR47063, 37 degrees C; n = 9 4) followed by cardioplegic arrest and rewarming. Myocyte contractilit y was measured after rewarming by videomicroscopy. The second study de termined whether the effects of PCO pretreatment could be translated t o an in vivo model of cardioplegic arrest. Pigs (weight 30 to 35 kg) w ere assigned to the following: (1) cardioplegia: institution of cardio pulmonary bypass (CPB) and cardioplegic arrest (Kf 24 mEq/L, 4 degrees Cx2 hours) followed by reperfusion and rewarming (n=8); and (2) PCO/c ardioplegia: institution of CPB, antegrade myocardial PCO perfusion wi thout recirculation (500 mt of 50 mu mol/L, SR47063, 37 degrees C), fo llowed by cardioplegic arrest (n = 6). LV function was examined at bas eline (pre-CPB) and at 0 to 30 minutes after separation from CPB by us e of the preload-recruitable stroke work relation (PRSWR; x 10(5) dyne cm/mm Hg). LV myocyte velocity of shortening was reduced after cardio plegic arrest and rewarming compared with normothermic control (37+/-3 vs 69+/-3 mu m/s, P<0.05) and was improved with 5 minutes of PCO trea tment (58+/-3 mu m/s). In the intact experiments, the slope of the PRS WR was depressed in the cardioplegia group compared with baseline with separation from CPB (1.07 +/- 0.15 vs 2.57 +/- 0.11, P<0.05) and rema ined reduced for up to 30 minutes after CPB. In the PCO-pretreated ani mals, the PRSWR was higher after cessation of CPB when compared with t he untreated cardioplegia group (1.72+/-0.07, P<0.05). However, in the PCO pretreatment group, 50% developed refractory ventricular fibrilla tion by 5 minutes after CPB, which prevented further study. Conclusion s-PCO pretreatment improved LV myocyte contractile function in an in v itro system of cardioplegic arrest. The in vivo translation of this im provement in contractile performance with PCO pretreatment was confoun ded by refractory arrhythmogenesis. Thus the application of PCO pretre atment as a protective strategy in the setting of cardiac surgery may be problematic.