Prominent differences in left ventricular performance and myocardial properties between right ventricular and left ventricular-based pacing modes in rats

Wesam Mulla,Sigal Elyagon,Noah Liel-Cohen,Roni Gillis,Ingra Mannhardt,Yoram Etzion,Thomas Eschenhagen,Sharon Etzion,Yuval Konstantino,Michael Murninkas

doi:10.1038/s41598-017-06197-w

Abstract

Biventricular pacing is an important modality to improve left ventricular (LV) synchronization and long-term function. However, the biological effects of this treatment are far from being elucidated and existing animal models are limited and demanding. Recently, we introduced an implanted device for double-site epicardial pacing in rats and echocardiographically demonstrated favorable effects of LV and biventricular (LV-based) pacing modes typically observed in humans. Here, this new animal model was further characterized. Electrodes were implanted either on the right atria (RA) and right ventricle (RV) or on the RV and LV. Following recovery, rats were either used for invasive hemodynamic measurements (pressure-volume analysis) or exposed to sustained RV vs. biventricular tachypacing for 3 days. RV pacing compromised, while LV-based pacing modes markedly enhanced cardiac performance. Changes in LV performance were associated with prominent compensatory changes in arterial resistance. Sustained RV tachypacing increased the electrocardiogram QTc interval by 7.9 ± 3.1 ms (n = 6, p < 0.05), dispersed refractoriness between the right and left pacing sites and induced important molecular changes mainly in the early-activated septal tissue. These effects were not observed during biventricular tachypacing (n = 6). Our results demonstrate that the rat is an attractive new model to study the biological consequences of LV dyssynchrony and resynchronization.

Highlights

The electromechanical and molecular consequences of various ventricular pacing modes have become a subject of intense interest in recent years due to profound clinical implications[1,2,3]
We found that right ventricle (RV) pacing induces marked left ventricular (LV) dyssynchrony compared to right atrial (RA) pacing or sinus rhythm
In the absence of technical means to induce left bundle branch block (LBBB), iatrogenic induction of electromechanical dyssynchrony relies on overdrive RV pacing in our rat model[25]

Summary

Introduction

The electromechanical and molecular consequences of various ventricular pacing modes have become a subject of intense interest in recent years due to profound clinical implications[1,2,3]. Using double site bipolar electrode implantation in combination with electrical recordings and speckle-tracking echocardiography, we managed to characterize for the first time the effects of various ventricular pacing modes on LV electromechanical synchrony in rats[25]. LV pacing and, to a greater extent BiV pacing, diminished LV dyssynchrony[25] These findings support the notion that rodent cardiac pacing mimics important electromechanical features seen in humans. In the present study we used pressure-volume (PV) loop recordings to characterize the effects of different ventricular pacing modes on cardiac performance. We found that sustained RV tachypacing induces prominent electrical and biochemical changes in myocardial properties compared to BiV pacing, including the activation of JNK in the early-activated myocardium, which was not previously identified in this setting. Our data mark this model as an attractive new tool to study the complex pathophysiology of ventricular dyssynchrony and resynchronization

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