B-PO02-024 ATP-SENSITIVE POTASSIUM CURRENT OPENER LEVOSIMENDAN MODULATES ACTION POTENTIAL DURATION ALTERNANS PROPERTIES AND PREVENTS VENTRICULAR ARRHYTHMIA DURING THERAPEUTIC HYPOTHERMIA

Abstract

Therapeutic hypothermia (TH) increases the risk of ventricular arrhythmia (VA) by prolonging the action potential duration (APD) and enhancing the spatial discordant alternans (SDA) on APD. We hypothesized that levosimendan, an ATP-sensitive potassium current opener, might shorten the already prolonged APD, attenuate the SDA on APD, and prevent VA during TH. Langendorff-perfused isolated rabbit hearts were subjected to 15-min TH (30°C) followed by 30-min treatment with levosimendan (0.5 μM, n=9) or vehicle (n=8). Using an optical mapping system, APD was evaluated by S1 pacing. The threshold of SDA on APD was defined as the longest S1 pacing cycle length (PCL) at which SDA on APD was detected. Ventricular fibrillation (VF) inducibility was evaluated by burst pacing for 30 s at the shortest PCL that achieved 1:1 ventricular capture. The APD was shortened from 259±8 ms at TH to 241±18 ms after levosimendan infusion at PCL of 400 ms (p=0.024). The threshold for SDA on APD was also shortened from 327±88 ms at TH to 311±68 ms after levosimendan infusion (p=0.003). The VF inducibility was decreased by levosimendan from 39±30% at TH to 14±12% with levosimendan (p=0.023). In control hearts, the APD, SDA threshold on APD (p=0.74), and VF inducibility (p=0.12) were not changed by vehicle during TH. Levosimendan might protect the hearts against VA during TH by shortening the APD and attenuate SDA on APD. Enhancing ATP-sensitive potassium current with levosimendan during TH might be a novel approach to prevent VA during TH.