Progression of Infarct-mediated Arrhythmogenesis in a Rodent Model of Heart Failure.

Heart failure (HF) post-myocardial infarction (MI) presents with increased vulnerability to monomorphic ventricular tachycardia (mmVT). In order to appropriately evaluate new therapies for infarct-mediated reentrant arrhythmia in the preclinical setting, chronologic characterization of the preclinical animal model pathophysiology is critical. This study aimed to evaluate the rigor and reproducibility of mmVT incidence in a rodent model of HF. We hypothesize a progressive increase in the incidence of mmVT as the duration of HF increases. Adult male Sprague Dawley rats underwent permanent left coronary artery ligation or SHAM surgery and were maintained for either six or ten weeks. At endpoint, SHAM and HF rats underwent echocardiographic and invasive hemodynamic evaluation. Finally, rats underwent electrophysiologic (EP) assessment to assess susceptibility to mmVT and define ventricular effective refractory period (ERP). In six-week HF rats (n=20), left ventricular (LV) ejection fraction (EF) decreased (p0.05), (p>0.05). Electrophysiology studies revealed an increase in incidence of mmVT between SHAM and six-week HF (p=0.0016) and ERP prolongation (p=0.0186). The incidence of mmVT and ventricular ERP did not differ between six- and ten-week HF (p=1.0000), (p=0.9831). Findings from this rodent model of HF suggest that once the ischemia-mediated infarct stabilizes, proarrhythmic deterioration ceases. Within the six- and ten-week period post-MI, no echocardiographic, invasive hemodynamic, nor electrophysiologic changes were observed, suggesting stable HF. This is the necessary context for the evaluation of experimental therapies in rodent HF.