背景:成功复苏后的室性心动过速(VT)/室颤(VF)再次停止很常见,生存是贫穷的。VT/VF的机制,如体外研究所示,当复极化交替变得空间不一致(DISALT)时,可以通过受损的间隙连接(GJs)来增强。然而,体内自发性DISALT诱导的VT/VF从未被证实,GJ对DISALT和VT/VF再停滞的影响尚不清楚。
目的:本研究旨在确定DISALT诱导的自发性室性心动过速/VF再停滞是否在体内发生,以及是否可以通过保留Cx43介导的GJ偶联和/或连接来抑制。
方法:我们在猪左心室楔形制剂中使用了缺血诱发的心脏骤停复苏的体内猪模型结合离体光学标测。
结果:体内,DISALT常先于VT/VF,且在正常(37°C,n=9)和亚低温(33°C,n=8)温度。用rotigaptide(n=10)维持体内GJs可降低DISALT和VT/VF发生率,尤其是在亚低温期间,90%和60%,分别(P<0.001;P<0.013)。离体,rotigaptide(n=5)和αCT11(n=7),一种促进GJ连接的Cx43模拟肽,显著降低DISALT60%和100%,分别为(P<0.05;P<0.005),这种减少与动作电位持续时间的内在异质性减少有关,而不是传导速度恢复的变化。
结论:这些结果提供了迄今为止最强的体内证据,表明在临床现实的情况下,自发性DISALT和VT/VF之间存在因果关系。此外,我们的结果表明,在复苏期间保留GJs可以抑制VT/VF再停滞.
BACKGROUND: Ventricular tachycardia (VT)/ventricular fibrillation (VF) rearrest after successful resuscitation is common, and survival is poor. A mechanism of VT/VF, as demonstrated in ex vivo studies, is when repolarization alternans becomes spatially discordant (DIS ALT), which can be enhanced by impaired gap junctions (GJs). However, in vivo spontaneous DIS ALT-induced VT/VF has never been demonstrated, and the effects of GJ on DIS ALT and VT/VF rearrest are unknown.
OBJECTIVE: This study aimed to determine whether spontaneous VT/VF rearrest induced by DIS ALT occurs in vivo, and if it can be suppressed by preserving Cx43-mediated GJ coupling and/or connectivity.
METHODS: We used an in vivo porcine model of resuscitation from ischemia-induced cardiac arrest combined with ex vivo optical mapping in porcine left ventricular wedge preparations.
RESULTS: In vivo, DIS ALT frequently preceded VT/VF and paralleled its incidence at normal (37°C, n = 9) and mild hypothermia (33°C, n = 8) temperatures. Maintaining GJs in vivo with rotigaptide (n = 10) reduced DIS ALT and VT/VF incidence, especially during mild hypothermia, by 90% and 60%, respectively (P < 0.001; P < 0.013). Ex vivo, both rotigaptide (n = 5) and αCT11 (n = 7), a Cx43 mimetic peptide that promotes GJ connectivity, significantly reduced DIS ALT by 60% and 100%, respectively (P < 0.05; P < 0.005), and this reduction was associated with reduced intrinsic heterogeneities of action potential duration rather than changes in conduction velocity restitution.
CONCLUSIONS: These results provide the strongest in vivo evidence to date suggesting a causal relationship between spontaneous DIS ALT and VT/VF in a clinically realistic scenario. Furthermore, our results suggest that preserving GJs during resuscitation can suppress VT/VF rearrest.