Department of Cardiology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Acta Pharmacol Sin. 2012 Dec;33(12):1488-94. doi: 10.1038/aps.2012.96. Epub 2012 Oct 15.
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.
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.
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.
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.
在犬心室颤动模型中，确定电击成功和失败后的后除极激活模式，以及匹那地尔（早期后除极抑制剂）是否改变除颤阈值（DFT）和电击后的激活模式。
在 6 只比格犬中，将带有 64 个单极电极的篮状导管置于左心室进行全心内膜标测，将单极动作电位导管插入左心室心尖部，将带有右心室负电极和上腔静脉正电极的导管插入进行除颤。在给予匹那地尔后（负荷剂量 0.5mg/kg，维持剂量 0.5mg·kg^-1·h^-1，iv）评估 DFT、90%动作电位时程（APD（90））和激活恢复间期（ARI）。用 ARI 的离散度定义电异质性。用接近 DFT 强度进行电击成功和失败后，检测最早的电击后激活模式（局灶性或非局灶性心内膜激活）、间期和位置。
匹那地尔显著降低 APD（90）（从 178±16ms 降至 168±18ms）和 ARI（从 152±10ms 降至 143±10ms），起搏周长为 300ms。药物显著增加 VF 激活率（从 10.0±1.9Hz 增加到 10.8±2.0Hz）。药物不影响 ARI 的离散度，也不改变 DFT（基线：480±110V；匹那地尔：425±55V，P>0.05）。药物治疗前后，最早的电击后激活出现在左心室心尖部的局部。匹那地尔显著延长了成功电击后的第 2 至 5 个电击周期，但对失败电击无效。
匹那地尔增加了电击后的周期长度，提示早期后除极可能在电击后激活中起作用，而不改变 DFT 提示电击产生的早期后除极并不决定除颤的成功或失败。
