PRESERVATION OF MYOCYTE CONTRACTILE FUNCTION AFTER HYPOTHERMIC CARDIOPLEGIC ARREST BY ACTIVATION OF ATP-SENSITIVE POTASSIUM CHANNELS

Background Left ventricular (LV) dysfunction can occur after hyperkale mic cardioplegic arrest and subsequent reperfusion and rewarming. Acti vation of adenosine triphosphate (ATP)-sensitive potassium (KATP) chan nels within the myocyte sarcolemma has been shown to be cardioprotecti ve for myocardial reperfusion injury and ischemia and may play a contr ibutory role in preconditioning for cardioplegic arrest. Accordingly, the present study tested the hypothesis that cardioplegic arrest and a ctivation of KATP channels by a potassium channel opener (PCO) would a ttenuate alterations in ionic homeostasis and improve myocyte contract ile function. Methods and Results Porcine LV myocytes were isolated an d randomly assigned to the following treatment groups: normothermic co ntrol, incubation in cell culture media for 2 hours at 37 degrees C (n =60); hyperkalemic cardioplegia, incubation for 2 hours in hypothermic hyperkalemic cardioplegic solution (n=60); or PCO/cardioplegia, incub ation in cardioplegic solution containing 100 mu mol/L of the PCO apri kalim (n=60). Hyperkalemic cardioplegia and rewarming caused a signifi cant reduction in myocyte velocity of shortening compared with normoth ermic control values (33+/-2 versus 66+/-2 mu m/s, P<.05). Cardioplegi c arrest with PCO supplementation significantly improved indices of my ocyte contractile function when compared with hyperkalemic cardioplegi a (58+/-4 mu m/s, P<.05). Myocyte intracellular calcium increased duri ng hyperkalemic cardioplegic arrest compared with baseline values (147 +/-2 versus 85+/-2 nmol/L, P<.05). The increase in intracellular calci um was significantly reduced in myocytes exposed to the PCO-supplement ed cardioplegic solution (109+/-4 nmol/L, P<.05). Conclusions Cardiopl egic arrest with simultaneous activation of KATP channels preserves my ocyte contractile processes and attenuates the accumulation of intrace llular calcium, These findings suggest that changes in intracellular c alcium play a role in myocyte contractile dysfunction associated with cardioplegic arrest. Moreover, alternative strategies may exist for pr eservation of myocyte contractile function during cardioplegic arrest.