Abstract
BackgroundRight ventricular (RV) pacing generates regional disparities in electrical activation and mechanical function (ventricular dyssynchrony). In contrast, left ventricular (LV) or biventricular (BIV) pacing can improve cardiac efficiency in the setting of ventricular dyssynchrony, constituting the rationale for cardiac resynchronization therapy (CRT). Animal models of ventricular dyssynchrony and CRT currently relay on large mammals which are expensive and not readily available to most researchers. We developed a methodology for double-site epicardial pacing in conscious rats. Here, following post-operative recovery, we compared the effects of various pacing modes on LV dyssynchrony in normal rats and in rats with ischemic cardiomyopathy.MethodsTwo bipolar electrodes were implanted in rats as follows: Group A (n = 6) right atrial (RA) and RV sites; Group B (n = 7) RV and LV sites; Group C (n = 8) as in group B in combination with left coronary artery ligation. Electrodes were exteriorized through the back. Following post-operative recovery, two-dimensional transthoracic echocardiography was performed during pacing through the different electrodes. Segmental systolic circumferential strain (Ecc) was used to evaluate LV dyssynchrony.ResultsIn normal rats, RV pacing induced marked LV dyssynchrony compared to RA pacing or sinus rhythm, as measured by the standard deviation (SD) of segmental time to peak Ecc, SD of peak Ecc, and the average delay between opposing ventricular segments. LV pacing and, to a greater extend BIV pacing diminished the LV dyssynchrony compared to RV pacing. In rats with extensive MI, the effects of LV and BIV pacing were markedly attenuated, and the response of individual animals was variable.ConclusionsRodent cardiac pacing mimics important features seen in humans. This model may be developed as a simple new tool to study the pathophysiology of ventricular dyssynchrony and CRT.
Highlights
Dyssynchronous contraction of the left ventricle (LV) can markedly worsen the outcome of heart failure (HF) independently of traditional risk factors [1,2]
As a first step we aimed to compare the effect of Right ventricular (RV) pacing to both no pacing and right atrial (RA) pacing modes
This analysis was done in order to confirm that the override pacing itself does not induce rate-dependent LV dyssynchrony compared to the no pacing mode
Summary
Dyssynchronous contraction of the left ventricle (LV) can markedly worsen the outcome of heart failure (HF) independently of traditional risk factors [1,2]. Dyssynchronous heart failure (DHF) has been extensively studied in mechanical terms and the clinical effectiveness of CRT is remarkable, there are multiple issues that remain ill-defined at present It is, for example, estimated that around 30% of patients do not benefit from CRT, and the clinical criteria to identify CRT non-responders remain obscure and controversial. Animal studies have shown that DHF is associated with regional molecular changes (collectively termed ‘molecular polarization’), including downregulation of Ca2+ handling proteins and connexin 43, activation of stress response kinases and increased expression of tumor necrosis factor in the lateral LV wall. Most of these changes can be reversed by CRT [11]. Following postoperative recovery, we compared the effects of various pacing modes on LV dyssynchrony in normal rats and in rats with ischemic cardiomyopathy
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