The effect of pinacidil on postshock activation and ventricular defibrillation threshold in canine hearts

Abstract

Aim: To determine the postshock activation patterns with both successful and failed shocks in a canine model of ventricular fibrillation, and whether piniacidil, an early after-depolarization (EAD) inhibitor, altered the defibrillation threshold (DFT) and postshock activation patterns. Methods: In 6 beagles, a basket catheter with 64 unipolar electrodes was placed in the LV for global endocardial mapping, a monophasic action potential catheter was inserted into the LV apex, and a catheter with the negative electrode in the right ventricle and the positive electrode in the superior vena cava was inserted for defibrillation. The DFT, 90% action potential duration (APD 90) and activation recovery interval (ARI) were evaluated before and after pinacidil administration (loading dosage 0.5 mg/kg and maintenance dosage 0.5 mg·kg-1 ·h-1, iv). Electrical heterogeneities were defined with the dispersion of ARI. After successful and failed shocks with near-DFT strength, the earliest postshock activation patterns (focal or nonfocal endocardial activation), interval and location were detected.Results:Pinacidil significantly decreased APD 90 (from 178±16 ms to 168±18 ms) and ARI from (152±10 ms to 143±10 ms) at pacing cycle length of 300 ms. The drug significantly increased VF activation rate (from 10.0±1.9 Hz to 10.8±2.0 Hz). The drug did not affect the dispersion of ARI, neither it changed DFT (baseline: 480±110 V; pinacidil: 425±55 V, P>0.05). The earliest postshock activation arose locally on the LV apical endocardium before and after the drug treatment. Pinacidil significantly prolonged the postshock cycle length of cycles 2 to 5 for the successful episodes but not for the failed episodes.Conclusion:Pinacidil increases the postshock cycle length suggesting that EAD may play a role in postshock activation, while it fails to alter DFT suggesting that EAD produced by shock does not determine a defibrillation success or failure. © 2012 CPS and SIMM All rights reserved.