Recovery in ERG gene expression with biventricular pacing in a rabbit model of myocardial infarction

Abstract

Samir Saba,* Haider Mehdi,* William Barrington, Fardeen Mehdi, Zahid Islam, Barry LondonCardiovascular Institute of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA*These authors contributed equally to this workBackground: Improved clinical and echocardiographic parameters have been documented with biventricular (BIV) pacing in patients after myocardial infarction (MI). We investigated the changes in gene expression in cardiac tissue with BIV pacing, using a rabbit model of MI.Method: New Zealand White rabbits were divided into four groups: sham-operated controls, MI with no pacing, MI with right ventricle (RV) pacing (MI + RV), and MI with BIV pacing (MI + BIV). Pacing was initiated 1–2 weeks after the coronary ligation. At 5 weeks, the hearts were excised. The tissue extracted from the left ventricle (LV) and RV underwent analysis for protein and messenger ribonucleic acid (mRNA) levels.Results: The ether-a-go-go-related gene (ERG) protein levels recovered from the base of the LV away from the MI area were two- to threefold lower in the MI and the MI + RV compared with the MI + BIV groups (P = 0.07). The ERG protein levels were similar between the MI + BIV and the control groups. However, the RNA levels were comparable between the four study groups, suggesting that a posttranscriptional mechanism accounted for the difference in protein levels.Conclusion: In this rabbit model of MI, we demonstrated a recovery in ERG protein levels with BIV pacing, after MI. This recovery may underlie some of the benefits seen with BIV pacing in ischemic cardiomyopathy.Keywords: heart failure, biventricular pacing, cardiac reverse remodeling, ether-a-go-go-related gene