Preservation of Myocyte Contractile Function After Hypothermic Cardioplegic Arrest by Activation of ATP-Sensitive Potassium Channels

Abstract

Background Left ventricular (LV) dysfunction can occur after hyperkalemic cardioplegic arrest and subsequent reperfusion and rewarming. Activation of adenosine triphosphate (ATP)-sensitive potassium (K atp ) channels within the myocyte sarcolemma has been shown to be cardioprotective for myocardial reperfusion injury and ischemia and may play a contributory role in preconditioning for cardioplegic arrest. Accordingly, the present study tested the hypothesis that cardioplegic arrest and activation of K atp channels by a potassium channel opener (PCO) would attenuate alterations in ionic homeostasis and improve myocyte contractile function. Methods and Results Porcine LV myocytes were isolated and randomly assigned to the following treatment groups: normothermic control, incubation in cell culture media for 2 hours at 37°C (n=60); hyperkalemic cardioplegia, incubation for 2 hours in hypothermic hyperkalemic cardioplegic solution (n=60); or PCO/cardioplegia, incubation in cardioplegic solution containing 100 μmol/L of the PCO aprikalim (n=60). Hyperkalemic cardioplegia and rewarming caused a significant reduction in myocyte velocity of shortening compared with normothermic control values (33±2 versus 66±2 μm/s, P <.05). Cardioplegic arrest with PCO supplementation significantly improved indices of myocyte contractile function when compared with hyperkalemic cardioplegia (58±4 μm/s, P <.05). Myocyte intracellular calcium increased during hyperkalemic cardioplegic arrest compared with baseline values (147±2 versus 85±2 nmol/L, P <.05). The increase in intracellular calcium was significantly reduced in myocytes exposed to the PCO-supplemented cardioplegic solution (109±4 nmol/L, P <.05). Conclusions Cardioplegic arrest with simultaneous activation of K atp channels preserves myocyte contractile processes and attenuates the accumulation of intracellular calcium. These findings suggest that changes in intracellular calcium play a role in myocyte contractile dysfunction associated with cardioplegic arrest. Moreover, alternative strategies may exist for preservation of myocyte contractile function during cardioplegic arrest.