吡那地尔对犬心电击后除颤阈值和心肌除颤后激活的影响。
The effect of pinacidil on postshock activation and ventricular defibrillation threshold in canine hearts.
机构信息
Department of Cardiology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
出版信息
Acta Pharmacol Sin. 2012 Dec;33(12):1488-94. doi: 10.1038/aps.2012.96. Epub 2012 Oct 15.
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.
目的
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。
方法
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。
结果
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。
结论
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。
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