Department of Cardiology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Internal Medicine, CARMA Center, University of Utah, Salt Lake City, UT, USA.
Cardiovasc Ther. 2018 Jun;36(3):e12326. doi: 10.1111/1755-5922.12326. Epub 2018 Mar 25.
Sotalol and verapamil alone reduce reentry incidence during ventricular fibrillation (VF). We tested whether the combination of these two drugs had a synergistic effect on initiation, maintenance, and termination of VF.
Six open-chest pigs received intravenous sotalol (1.5 mg/kg) followed by verapamil (0.136 mg/kg). VF threshold (VFT) was determined by a burst pacing protocol. Two 20 seconds episodes of VF were recorded from a 21 × 24 unipolar electrode plaque on the lateral posterior left ventricular epicardium before and after each drug. VF activation patterns were quantified. The duration of long duration VF (LDVF) maintenance was compared to our previously published data.
Sotalol alone and combined with verapamil significantly increased the VFT from 12.3 ± 4.1 to 20.3 ± 7.1 and 26.7 ± 8.6 mA compared with baseline (P < .05). Sotalol decreased the number of wavefronts by 20%, VF activation rate by 17% and conduction velocity 11%, while the addition of verapamil neutralized these effects. Addition of verapamil to sotalol further decreased the fractionation incidence from 14% to 29% and multiplicity from 24% to 31% compared with baseline. The combination of the two drugs increased the VF cycle length, decreased synchronicity, increased regularity index and shortened the duration of LDVF maintenance compared with our previous data of verapamil alone or no drug. Synchronicity index was lower and regularity index was higher in animals in which VF spontaneously terminated earlier than 10 minutes than in animals in which VF terminated longer than 10 minutes.
The combination of sotalol and verapamil increased VFT but accelerated LDVF termination.
索他洛尔和维拉帕米单独使用均可减少心室颤动（VF）时折返的发生率。我们测试了这两种药物联合使用是否对 VF 的起始、维持和终止有协同作用。
六只开胸猪静脉注射索他洛尔（1.5mg/kg），然后静脉注射维拉帕米（0.136mg/kg）。通过爆发起搏方案确定心室颤动阈值（VFT）。在左心室外侧后表面的 21×24 个单极电极斑块上记录两次 20 秒的 VF 发作，每次药物治疗前后各记录一次。量化 VF 激活模式。比较长持续时间 VF（LDVF）维持的持续时间与我们之前发表的数据。
与基线相比，索他洛尔单独使用和联合使用维拉帕米后，VFT 分别显著增加了 20.3±7.1 和 26.7±8.6mA（P<0.05）。索他洛尔使波阵面减少 20%，VF 激活率减少 17%，传导速度减少 11%，而维拉帕米的加入则使这些作用中和。与基线相比，维拉帕米联合索他洛尔进一步使碎裂发生率从 14%降至 29%，多发性从 24%降至 31%。与单独使用维拉帕米或无药物治疗相比，两药联合使用增加了 VF 周期长度，降低了同步性，增加了规则指数，并缩短了 LDVF 维持时间。与 VF 自动终止时间早于 10 分钟的动物相比，同步性指数较低，规则指数较高的动物，VF 终止时间较长。
索他洛尔和维拉帕米联合使用增加了 VFT，但加速了 LDVF 的终止。
