Data from: Effects of the selective stretch-activated channel blocker GsMtx4 on stretch-induced changes in refractoriness in isolated rat hearts and on ventricular premature beats and arrhythmias after coronary occlusion in swine

Mechanical factors may contribute to ischemic ventricular arrhythmias. GsMtx4 peptide, a selective stretch-activated channel blocker, inhibits stretch-induced atrial arrhythmias. We aimed to assess whether GsMtx4 protects against ventricular ectopy and arrhythmias following coronary occlusion in swine. First, the effects of 170-nM GsMtx4 on the changes in the effective refractory period (ERP) induced by left ventricular (LV) dilatation were assessed in 8 isolated rat hearts. Then, 44 anesthetized, open-chest pigs subjected to 50-min left anterior descending artery occlusion and 2-h reperfusion were blindly allocated to GsMtx4 (57 μg/kg iv. bolus and 3.8 μg/kg/min infusion, calculated to attain the above concentration in plasma) or saline, starting 5-min before occlusion and continuing until after reflow. In rat hearts, LV distension induced progressive reductions in ERP (35±2, 32±2, and 29±2 ms at 0, 20, and 40 mmHg of LV end-diastolic pressure, respectively, P<0.001) that were prevented by GsMTx4 (33±2, 33±2, and 32±2 ms, respectively, P=0.002 for the interaction with LV end-diastolic pressure). Pigs receiving GsMtx4 had similar number of ventricular premature beats during the ischemic period as control pigs (110±28 vs. 103±21, respectively, P=0.842). There were not significant differences among treated and untreated animals in the incidence of ventricular fibrillation (13.6 vs. 22.7%, respectively, P=0.696) or tachycardia (36.4 vs. 50.0%, P=0.361) or in the number of ventricular tachycardia episodes during the occlusion period (1.8±0.7 vs. 5.5±2.6, P=0.323). Thus, GsMtx4 administered under these conditions does not suppress ventricular ectopy following coronary occlusion in swine. Whether it might protect against malignant arrhythmias should be tested in studies powered for these outcomes.

机械因素可能参与缺血性室性心律失常的发生。GsMtx4肽是一种选择性牵张激活通道阻滞剂（stretch-activated channel blocker），可抑制牵张诱导的房性心律失常。本研究旨在评估GsMtx4是否能保护猪免受冠状动脉闭塞后出现的室性异位搏动与心律失常。首先，我们在8个离体大鼠心脏标本中，评估了170nM的GsMtx4对左心室（left ventricular, LV）扩张诱导的有效不应期（effective refractory period, ERP）变化的影响。随后，将44只麻醉开胸猪采用双盲随机分组，分别于左前降支冠状动脉闭塞前5分钟开始给药并持续至再灌注结束后：一组给予GsMtx4治疗（静脉推注57μg/kg，随后以3.8μg/kg/min的速率持续输注，经药代动力学计算可使血浆药物浓度达到前述170nM水平），另一组给予生理盐水对照；所有实验猪均接受50分钟左前降支闭塞及2小时再灌注处理。在离体大鼠心脏实验中，左心室扩张可导致有效不应期进行性缩短（当左心室舒张末期压分别为0、20、40mmHg时，有效不应期依次为35±2、32±2及29±2ms，P<0.001），而GsMtx4可阻断这一效应（给药后依次为33±2、33±2及32±2ms，与左心室舒张末期压的交互效应P=0.002）。缺血期间，GsMtx4给药组与对照组猪的室性早搏数量无显著统计学差异（分别为110±28与103±21，P=0.842）。两组间心室颤动发生率（分别为13.6%与22.7%，P=0.696）、室性心动过速发生率（分别为36.4%与50.0%，P=0.361），以及闭塞期室性心动过速发作次数（分别为1.8±0.7与5.5±2.6，P=0.323）均无统计学差异。综上，在本实验条件下给予GsMtx4，无法抑制猪冠状动脉闭塞后的室性异位搏动。针对其是否可防护恶性心律失常，仍需通过效力充足的相关研究进一步验证。