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

作　　者：Qi JIN Ning ZHANG Jian ZHOU Chang-jian LIN Yang PANG Gang GU Wei-feng SHEN Li-qun WU 

机构地区：[1]Department of Cardiology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

出　　处：《Acta Pharmacologica Sinica》2012年第12期1488-1494,共7页中国药理学报（英文版）

摘　　要：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 mono- phasic 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 （APDgo） and activa- tion recovery interval （ARI） were evaluated before and after pinacidil administration （loading dosage 0.5 mg/kg and maintenance dos- age 0.5 mg-kg＇l.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 APD9o （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.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 mono- phasic 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 （APDgo） and activa- tion recovery interval （ARI） were evaluated before and after pinacidil administration （loading dosage 0.5 mg/kg and maintenance dos- age 0.5 mg-kg＇l.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 APD9o （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.

关 键 词：PINACIDIL heart ventricular fibrillation early after-depolarization （EAD） defibrillation threshold postshock activation 

分 类 号：TP391.41[自动化与计算机技术—计算机应用技术] TQ658.34[自动化与计算机技术—计算机科学与技术]