Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago.
CorDynamics, Inc.;
J Vis Exp. 2023 Jan 20(191). doi: 10.3791/63775.
Pulmonary arterial hypertension (PAH) is a progressive disease caused by vasoconstriction and remodeling of the small arteries in the lungs. This remodeling leads to increased pulmonary vascular resistance, worsened right ventricular function, and premature death. Currently approved therapies for PAH largely target pulmonary vasodilator pathways; however, recent emerging therapeutic modalities are focused on other novel pathways involved in the pathogenesis of the disease, including right ventricle (RV) remodeling. Imaging techniques that allow longitudinal assessment of novel therapeutics are very useful for determining the efficacy of new drugs in preclinical studies. Noninvasive trans-thoracic echocardiography remains the standard approach to evaluating heart function and is widely used in rodent models. However, echocardiographic evaluation of the RV can be challenging due to its anatomical position and structure. In addition, standardized guidelines are lacking for echocardiography in preclinical rodent models, making it difficult to carry out a uniform assessment of RV function across studies in different laboratories. In preclinical studies, the monocrotaline (MCT) injury model in rats is widely used to evaluate drug efficacy for treating PAH. This protocol describes the echocardiographic evaluation of the RV in naïve and MCT-induced PAH rats.
肺动脉高压(PAH)是一种由肺部小动脉收缩和重塑引起的进行性疾病。这种重塑导致肺血管阻力增加,右心室功能恶化,以及过早死亡。目前批准的 PAH 治疗方法主要针对肺血管扩张途径;然而,最近出现的治疗方法侧重于疾病发病机制中涉及的其他新途径,包括右心室(RV)重塑。允许对新型治疗药物进行纵向评估的成像技术对于确定新药在临床前研究中的疗效非常有用。非侵入性经胸超声心动图仍然是评估心脏功能的标准方法,在啮齿动物模型中广泛使用。然而,由于 RV 的解剖位置和结构,超声心动图评估 RV 具有挑战性。此外,临床前啮齿动物模型中缺乏超声心动图的标准化指南,使得难以在不同实验室的研究中对 RV 功能进行统一评估。在临床前研究中,大鼠的单克隆旋毛虫毒素(MCT)损伤模型被广泛用于评估治疗 PAH 的药物疗效。本方案描述了对 naive 和 MCT 诱导的 PAH 大鼠 RV 的超声心动图评估。