Document Type
Article
Publication Date
7-1-2024
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.
Keywords
cardiac alternans, connexin 43, gap junction, resuscitation, sudden cardiac arrest, ventricular fibrillation/tachycardia
Publication Title
JACC: Clinical Electrophysiology
Rights
© 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
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, Spontaneous Repolarization Alternans Causes VT/VF Rearrest That Is Suppressed by Preserving Gap Junctions, JACC: Clinical Electrophysiology, Volume 10, Issue 7, Part 1, 2024, Pages 1271-1286, ISSN 2405-500X, https://doi.org/10.1016/j.jacep.2024.03.027..
Manuscript Version
Final Publisher Version