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 (p<0.05) and LV end-diastolic pressure (EDP) increased (p<0.05) compared to SHAM (n=10). Ten-week HF (n=12) revealed maintenance of LVEF and LVEDP (p>0.05), (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.

中文翻译：

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啮齿类心力衰竭模型中梗死介导的心律失常发生的进展


心肌梗死（MI）后心力衰竭（HF）更容易出现单形性室性心动过速（mmVT）。为了在临床前环境中适当评估梗死介导的折返性心律失常的新疗法，临床前动物模型病理生理学的时间特征至关重要。本研究旨在评估 HF 啮齿动物模型中 mmVT 发生率的严谨性和重现性。我们假设随着心力衰竭持续时间的增加，mmVT 的发生率逐渐增加。成年雄性斯普拉道利大鼠接受了永久性左冠状动脉结扎或 SHAM 手术，并维持六周或十周。在终点时，SHAM 和 HF 大鼠接受超声心动图和侵入性血流动力学评估。最后，对大鼠进行电生理（EP）评估，以评估对 mmVT 的敏感性并确定心室有效不应期（ERP）。在六周的 HF 大鼠 (n=20) 中，左心室 (LV) 射血分数 (EF) 降低 (p<0 id=63>0.05)，(p>0.05)。电生理学研究显示，SHAM 与六周心力衰竭之间，mmVT 发生率增加 (p=0.0016)，ERP 延长 (p=0.0186)。心力衰竭六周和十周之间，mmVT 和心室 ERP 的发生率没有差异 (p=1.0000)、(p=0.9831)。这种心力衰竭啮齿动物模型的研究结果表明，一旦缺血介导的梗塞稳定下来，致心律失常的恶化就会停止。心肌梗死后六周和十周内，未观察到超声心动图、侵入性血流动力学或电生理变化，表明心力衰竭稳定。这是评估啮齿类心力衰竭实验疗法的必要背景。