Sarver Heart Center, University of Arizona, Tucson, Arizona.
MD-PhD Program, College of Medicine, University of Arizona, Tucson, Arizona.
Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H108-H116. doi: 10.1152/ajpheart.00639.2020. Epub 2020 Nov 8.
Heart failure (HF) post-myocardial infarction (MI) presents with increased vulnerability to monomorphic ventricular tachycardia (mmVT). 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 6 or 10 wk. At end point, 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 6-wk HF rats ( = 20), left ventricular (LV) ejection fraction (EF) decreased ( < 0.05) and LV end-diastolic pressure (EDP) increased ( < 0.05) compared with SHAM ( = 10). Ten-week HF ( = 12) revealed maintenance of LVEF and LVEDP ( > 0.05), ( > 0.05). Electrophysiology studies revealed an increase in incidence of mmVT between SHAM and 6-wk HF ( = 0.0016) and ERP prolongation ( = 0.0186). The incidence of mmVT and ventricular ERP did not differ between 6- and 10-wk HF ( = 1.0000), ( = 0.9831). Findings from this rodent model of HF suggest that once the ischemia-mediated infarct stabilizes, proarrhythmic deterioration ceases. Within the 6- and 10-wk period post-MI, no echocardiographic, invasive hemodynamic, or electrophysiologic changes were observed, suggesting stable HF. This is the necessary context for the evaluation of experimental therapies in rodent HF. Rodent model of ischemic cardiomyopathy exhibits a plateau of inducible monomorphic ventricular tachycardia incidence between 6 and 10 wk postinfarction.
心肌梗死后心力衰竭（HF）易发生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，对临床前动物模型病理生理学的时间特征进行严格评估至关重要。本研究旨在评估 HF 啮齿动物模型中 mmVT 发生率的严格性和可重复性。我们假设随着 HF 持续时间的增加，mmVT 的发生率会逐渐增加。成年雄性 Sprague-Dawley 大鼠接受永久性左冠状动脉结扎或 SHAM 手术，并维持 6 或 10 周。在终点，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，大鼠进行电生理（EP）评估以评估对 mmVT 的易感性并定义心室有效不应期（ERP）。在 6 周 HF 大鼠（n=20）中，左心室（LV）射血分数（EF）降低（<0.05），LV 舒张末期压力（EDP）升高（<0.05）与 SHAM（n=10）相比。10 周 HF（n=12）显示 LVEF 和 LVEDP 维持（>0.05），（>0.05）。电生理研究显示 SHAM 和 6 周 HF 之间 mmVT 发生率增加（=0.0016）和 ERP 延长（=0.0186）。6-和 10 周 HF 之间的 mmVT 发生率和心室 ERP 无差异（=1.0000），（=0.9831）。该 HF 啮齿动物模型的研究结果表明，一旦缺血介导的梗死稳定下来，心律失常恶化就会停止。在 MI 后 6-10 周期间，未观察到超声心动图、侵入性血流动力学或电生理变化，提示稳定的 HF。这是在 HF 啮齿动物中评估实验性治疗的必要背景。缺血性心肌病的啮齿动物模型在梗死后 6-10 周之间表现出可诱导单形性室性心动过速发生率的平台。
