Excitation-contraction coupling from the integration of action potential duration (APD) and muscle contractility plays an important role in arrhythmogenesis. We aimed to determine whether distinctive excitation-contraction coupling contributes to the genesis of ventricular tachycardias (VTs). Action potential (AP) and mechanical activity were simultaneously recorded under electrical pacing (cycle lengths from 1000 to 100 ms) in the tissue model created from isolated rabbit right ventricular outflow tracts treated with NS 5806 (10 μM, transient outward potassium current enhancer), pinacidil (2 μM, ATP-sensitive potassium channel opener), and pilsicainide (5 μM, sodium channel blocker). There were 15 (9.9%) inducible VT episodes (group 1) and 136 (90.1%) non-inducible VT episodes (group 2) in our tissue model. Group 1 had greater post-pacing increases of the first occurrence of AP at 90% repolarization (ΔAPD₉₀, p < 0.001) and contractility (ΔContractility, p = 0.003) compared with group 2. Triggered VT episodes were common (72.7%) in cases with a ΔAPD₉₀ > 15% and a ΔContractility > 270%, but were undetectable in those with a ΔAPD₉₀ < 15% and a ΔContractility < 270%. In those with pacing-induced VTs, KB-R7943 (10 μM, a Na⁺–Ca²⁺ exchanger inhibitor, NCX inhibitor) significantly reduced the occurrence of VTs from 100.0 to 20.0% (15/15 to 3/15 episodes, p < 0.001). Concurrent increases in both post-pacing APD and contractility resulted in the occurrence of ventricular arrhythmias. NCX inhibition may be a potential therapeutic strategy for ventricular arrhythmias.

来自动作电位持续时间 (APD) 和肌肉收缩力整合的兴奋-收缩耦合在心律失常中起着重要作用。我们旨在确定独特的兴奋-收缩耦合是否有助于室性心动过速 (VT) 的发生。在用 NS 5806（10 μM，瞬时外向钾电流增强剂）处理的离体兔右心室流出道创建的组织模型中，在电起搏（周期长度从 1000 到 100 ms）下同时记录动作电位 (AP) 和机械活动，匹那地尔（2 μM，ATP 敏感的钾通道开放剂）和 pilsicainide（5 μM，钠通道阻滞剂）。在我们的组织模型中，有 15 (9.9%) 次诱导性 VT 发作（第 1 组）和 136 (90.1%) 次非诱导性 VT 发作（第 2 组）。₉₀ , p < 0.001) 和收缩力 (ΔContractility, p = 0.003) 与第 2 组相比。触发 VT 发作在 ΔAPD ₉₀ > 15% 和 ΔContractility > 270% 的情况下很常见 (72.7%) ，但在那些情况下检测不到ΔAPD ₉₀ < 15% 和 ΔContractility < 270%。在起搏诱发的 VT 患者中，KB-R7943（10 μM，一种 Na ⁺ –Ca ²⁺交换剂抑制剂，NCX 抑制剂）显着降低了 VT 的发生率，从 100.0% 降至 20.0%（15/15 至 3/15 次发作，p< 0.001)。起搏后 APD 和收缩力同时增加导致室性心律失常的发生。NCX 抑制可能是室性心律失常的潜在治疗策略。