International Heart Journal
Online ISSN : 1349-3299
Print ISSN : 1349-2365
ISSN-L : 1349-2365
Experimental Studies
Exendin-4 Reduces Ventricular Arrhythmia Activity and Calcium Sparks-Mediated Sarcoplasmic Reticulum Ca Leak in Rats with Heart Failure
Jingjing ChenShunen XuWei ZhouLirong WuLong WangWei Li
Author information
JOURNAL FREE ACCESS

2020 Volume 61 Issue 1 Pages 145-152

Details
Abstract

The aim of this study was to investigate the effect of exendin-4 (Ex-4) on ventricular arrhythmias and calcium sparks-mediated calcium leak in a myocardial infarction-heart failure model.

We studied the influence of exendin-4 on ventricular arrhythmogenesis in a rat myocardial infarction-heart failure model. In vivo arrhythmia studies (electrocardiogram [ECG] telemetry studies), ex vivo arrhythmia studies calcium sparks tests, and analysis of total and phosphorylated ryanodine receptor (RyR) 2 and CaMK-II were carried out in sham group, myocardial infarction (MI) group, MI + Ex-4 and MI + Ex-4 + Exendin9-39 (Ex9-39) groups.

ECG telemetry studies showed an antiarrhythmic effect of exendin-4 with reduction of spontaneous ventricular arrhythmias. Exendin-4 abbreviated the APD90, which was longer in the heart failure model, and increase the APD alternans thresholds. Exendin-4 also reduced the susceptibility to burst pacing-induced arrhythmia ex vivo. Subcellular sarcoplasmic reticulum (SR) calcium leak characteristics were tested in four groups of rat cardiomyocytes. Exendin-4 reduced calcium spark mass, spark frequency, and calcium leak, which may be due to reduced S2814-RyR2 and CaMK-II phosphorylation. Co-administration of exendin 9-39 with exendin-4 partly abolished the above-mentioned effect of exendin-4.

These findings suggest that exendin-4 exerts an antiarrhythmic effect through decreasing SR calcium leak in spontaneous and burst pacing-induced ventricular arrhythmias, which may be due to reduced RyR2 phosphorylation and suppressed CaMK-II activity. Exendin-4 may act as a novel antiarrhythmic strategy in heart failure.

Content from these authors
© 2020 by the International Heart Journal Association
Previous article Next article
feedback
Top