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

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131453_2_merged_1457902754.pdfAccepted version2.94 MBAdobe PDFView/Open
131453_2_supp_8_63zv9t_convrt.pdfSupporting information18.82 MBAdobe PDFView/Open
1-s2.0-S2405500X16300718-main.pdfPublished version1.96 MBAdobe PDFView/Open
Title: Enhancement of Gap Junction Function During Acute Myocardial Infarction Modifies Healing and Reduces Late Ventricular Arrhythmia Susceptibility
Authors: Ng, FS
Kalindjian, JM
Cooper, SA
Chowdhury, RA
Patel, PM
Dupont, E
Lyon, AR
Peters, NS
Item Type: Journal Article
Abstract: Objectives: 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 characterisation of the rat 4-week post-MI model (n=24), a further 27 Sprague-Dawley rats were randomised to receive rotigaptide to enhance GJ coupling (n=13) or saline control (n=14) by osmotic minipump immediately prior to, and for the first 7 days following surgical 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 difference in infarct size at 4 weeks post-MI, rotigaptide-treated hearts had reduced arrhythmia susceptibility during PES (Inducibility score: rotigaptide 2.40.8, control 5.00.6, p=0.02) and less heterogeneous IBZ scarring (standard deviation of IBZ Complexity Score: rotigaptide 1.10.1, control 1.40.1, p=0.04), associated with an improvement in IBZ conduction velocity (rotigaptide 43.13.4 cm/s, control 34.82.0 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.
Issue Date: 25-May-2016
Date of Acceptance: 17-Mar-2016
URI: http://hdl.handle.net/10044/1/30422
DOI: http://dx.doi.org/10.1016/j.jacep.2016.03.007
ISSN: 2405-5018
Publisher: Elsevier
Start Page: 574
End Page: 582
Journal / Book Title: JACC. Clinical electrophysiology
Volume: 2
Issue: 5
Copyright Statement: THIS IS AN OPEN ACCESS ARTICLE UNDER THE CC BY LICENSE
Sponsor/Funder: British Heart Foundation
Medical Research Council (MRC)
British Heart Foundation
British Heart Foundation
Funder's Grant Number: RE/08/002
G0900396
FS/11/67/28954
RG/10/11/28457
Keywords: CV, conduction velocity
Cx43, connexin43
GJ, gap junction
IBZ, infarct border zone
MI, myocardial infarction
PBS, phosphate-buffered saline
PES, programmed electrical stimulation
VT, ventricular tachycardia
electrophysiology
fibrosis
gap junctions
myocardial infarction
ventricular arrhythmia
Publication Status: Published
Appears in Collections:National Heart and Lung Institute