Spontaneous Repolarization Alternans Causes VT/VF Rearrest That Is Suppressed by Preserving Gap Junctions.

Abstract

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.

OBJECTIVES:

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.

• Authors: Kenneth R Laurita, Joseph S Piktel, Laken Irish, Michelle Nassal, Aurelia Cheng, Matthew McCauley, Gary Pawlowski, Adrienne T Dennis, Yi Suen, Soufian Almahameed, Ohad Ziv, Robert G Gourdie, Lance D Wilson
• Journal: JACC. Clinical electrophysiology (JACC Clin Electrophysiol) (May 01 2024) ISSN: 2405-5018 [Electronic] United States
• PMID: 38752959 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.