The Individual Role of Sarcolemmal and Mitochondrial KATP Channels Opening During Cardiopulmonary Resuscitation in a Porcine Model Treated with Levosimendan

Objective: We investigated the individual role of the sarcolemmal KATP (sarcKATP) channel and the mitochondrial KATP (mitoKATP) channel opening during cardiac arrest and resuscitation by levosimendan administration to improve post-resuscitation myocardial function in a porcine model. Materials & Methods: Twenty pigs were randomized into 4 groups: 1) levosimendan (LEVO) + HMR-1098 (sarcKATP channel blocker): HMR-1098 3 mg/Kg was injected 30 min before inducing ventricular fibrillation (VF) and levosimendan 40 μg/kg was injected 3 min after inducing VF (VF 3); 2) LEVO + 5-HD (mitoKATP channel blocker): 5-HD 5 mg/Kg was injected 30 min before inducing VF and levosimendan 40 μg/kg was injected at VF 3; 3) LEVO: levosimendan 40 μg/kg was injected at VF 3; 4) control: an equal volume of saline placebo was injected at VF 3. VF was induced by intraluminal balloon occlusion of the left anterior descending coronary artery. After 7 min of untreated VF, CPR was initiated for 5 min followed by defibrillation. Resuscitated animals were observed for 4 hrs. Myocardial function was assessed by echocardiographic doppler measurements. To examine myocardial protection, we assessed measurements obtained from a PC-based data acquisition system, supported by CODAS/WINDAQ hardware/software, a stat profile analyzer and a lactic acid analyzer. Results: Pre-treatment of the sarcKATP channel blocker increased ventricular arrhythmia and the number of defibrillation shocks required. Blocking the mitoKATP channel completely abolished myocardial protective effects of LEVO. Beneficial effects of decreased ST segment elevation, reduced production of myocardial H+, and lactate and CO2 as observed following administration of LEVO no longer existed after blocking either channel. Conclusion: Activation of both channels by LEVO provides myocardial protective mechanisms. Activation of the sarcKATP channel reduces post-resuscitation ventricular arrhythmia, while activation of the mitoKATP channel improves myocardial mechanical function. Reduced myocardial H+, lactate and CO2 production was observed after activation of both channels. Copyright © 2017 The Authors. Published by Scientific Open Access Journals LLC.