Enhancement of Gap Junction Function During Acute Myocardial Infarction Modifies Healing and Reduces Late Ventricular Arrhythmia Susceptibility

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• 作者：Fu Siong Ng ; MBBS ; PhD ; ^{f.ng@imperial.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Jeremy M. Kalindjian ; MBBS ; Simon A. Cooper ; MBBS ; Rasheda A. Chowdhury ; PhD ; Pravina M. Patel ; BSc ; Emmanuel Dupont ; PhD ; Alexander R. Lyon ; BMBCh ; PhD ; Nicholas S. Peters ; MBBS ; MD
• 关键词：electrophysiology ; fibrosis ; gap junctions ; myocardial infarction ; ventricular arrhythmia
• 刊名：JACC: Clinical Electrophysiology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：2
• 期：5
• 页码：574-582
• 全文大小：1907 K

文摘

The purpose of this study was to investigate the effects of enhancing gap junction (GJ) coupling during acute myocardial infarction (MI) on the healed infarct scar morphology and late post-MI arrhythmia susceptibility.

Background

Increased heterogeneity of myocardial scarring after MI is associated with greater arrhythmia susceptibility. We hypothesized that short-term enhancement of GJ coupling during acute MI can produce more homogeneous infarct scars, reducing late susceptibility to post-MI arrhythmias.

Methods

Following arrhythmic characterization of a rat 4-week post-MI model (n = 24), another 27 Sprague-Dawley rats were randomized to receive rotigaptide to enhance GJ coupling (n = 13) or to saline control (n = 14) by osmotic minipump immediately prior to and for the first 7 days following surgically induced MI. At 4 weeks post-MI, hearts were explanted for ex vivo programmed electrical stimulation (PES) and optical mapping. Heterogeneity of infarct border zone (IBZ) scarring was quantified by histomorphometry.

Results

Despite no detectable differences in infarct size at 4 weeks post-MI, rotigaptide-treated hearts had reduced arrhythmia susceptibility during PES (inducibility score for rotigaptide: 2.4 ± 0.8; for control: 5.0 ± 0.6; p = 0.02) and less heterogeneous IBZ scarring (dispersion of IBZ complexity score: rotigaptide: 1.1 ± 0.1; control: 1.4 ± 0.1; p = 0.04), associated with an improvement in IBZ conduction velocity (rotigaptide: 43.1 ± 3.4 cm/s; control: 34.8 ± 2.0 cm/s; p = 0.04).

Conclusions

Enhancement of GJ coupling for only 7 days at the time of acute MI produced more homogeneous IBZ scarring and reduced arrhythmia susceptibility at 4 weeks post-MI. Short-term GJ modulation at the time of MI may represent a novel treatment strategy to modify the healed infarct scar morphology and reduce late post-MI arrhythmic risk.