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 ischemia. The goal of the present study was to examine whether PCO pretreatment would provide protective effects on left ventricular (LV) and myocyte function after cardioplegic arrest.

Methods And Results: The first study quantified the effects of PCO pretreatment on LV myocyte contractility after simulated cardioplegic arrest. LV porcine myocytes were randomly assigned to 3 groups: (1) normothermic control: 37 degrees C x 2 hours (n = 116); (2) cardioplegia: K+ 24 mEq/L, 4 degrees C x 2 hours followed by reperfusion and rewarming (n = 62); and (3) PCO/cardioplegia: 5 minutes of PCO treatment (50 mumol/L, SR47063, 37 degrees C; n = 94) followed by cardioplegic arrest and rewarming. Myocyte contractility was measured after rewarming by videomicroscopy. The second study determined whether the effects of PCO pretreatment could be translated to an in vivo model of cardioplegic arrest. Pigs (weight 30 to 35 kg) were assigned to the following: (1) cardioplegia: institution of cardiopulmonary bypass (CPB) and cardioplegic arrest (K+ 24 mEq/L, 4 degrees C x 2 hours) followed by reperfusion and rewarming (n = 8); and (2) PCO/cardioplegia: institution of CPB, antegrade myocardial PCO perfusion without recirculation (500 mL of 50 mumol/L, SR47063, 37 degrees C), followed by cardioplegic arrest (n = 6). LV function was examined at baseline (pre-CPB) and at 0 to 30 minutes after separation from CPB by use of the preload-recruitable stroke work relation (PRSWR; x 10(5) dyne.cm/mm Hg). LV myocyte velocity of shortening was reduced after cardioplegic arrest and rewarming compared with normothermic control (37 +/- 3 vs 69 +/- 3 microns/s, P < 0.05) and was improved with 5 minutes of PCO treatment (58 +/- 3 microns/s). In the intact experiments, the slope of the PRSWR 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 remained reduced for up to 30 minutes after CPB. In the PCO-pretreated animals, the PRSWR was higher after cessation of CPB when compared with the untreated cardioplegia group (1.72 +/- 0.07, P < 0.05). However, in the PCO pretreatment group, 50% developed refractory ventricular fibrillation by 5 minutes after CPB, which prevented further study.

Conclusions: PCO pretreatment improved LV myocyte contractile function in an in vitro system of cardioplegic arrest. The in vivo translation of this improvement in contractile performance with PCO pretreatment was confounded by refractory arrhythmogenesis. Thus the application of PCO pretreatment as a protective strategy in the setting of cardiac surgery may be problematic.