Distinct right ventricle remodeling in response to pressure overload in the rat
Distinct right ventricle remodeling in response to pressure overload in the rat
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DOI：
10.1152/ajpheart.00089.2016
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发表时间：
2016-07-01
影响因子：
4.8
通讯作者：
Bras-Silva, C.
中科院分区：
文献类型：
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作者：
Mendes-Ferreira, P.;Santos-Ribeiro, D.;Bras-Silva, C.
肺动脉高压（PAH）是最严重的慢性肺循环疾病，其特征是肺血管收缩和重塑，导致右心室（RV）后负荷增加。事实上，RV 功能是 PAH 预后的主要决定因素。最常用的 PAH 实验模型包括野百合碱和慢性缺氧诱导的 PAH，其主要影响肺循环。或者，可以进行肺动脉束带 (PAB) 以实现 RV 超载而不影响肺血管系统，从而使研究人员能够确定其药物/干预措施对 RV 的特异性影响。在这项工作中，我们使用两种不同程度的肺动脉收缩，详细描述了 PAB 手术后 3 周 PAB 诱导的 RV 适应性和适应不良重塑。我们的结果表明，应用轻度收缩会导致右心室适应性肥大，并保留收缩和舒张功能，而应用严重收缩会导致适应不良性肥大，导致心室扩张以及收缩和舒张功能障碍，直至分离的心肌细胞水平。通过应用两种不同程度的收缩，我们首次描述了一种可靠且持续时间短的 PAB 模型，其中可以在术后 3 周区分 RV 适应。我们详细描述了 RV 在对中度和重度收缩反应中的结构和功能变化，使研究人员能够更好地研究 RV 生理学以及向功能障碍和衰竭的转变，并确定新疗法的效果。
Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline-and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies.