Gillespie M N, Frederick W B, Altiere R J, Olson J W, Kimmel E C
Exp Lung Res. 1985;8(2-3):191-9. doi: 10.3109/01902148509057521.
Recent clinical studies have suggested that peripheral airways dysfunction contributes to the pathogenesis of idiopathic pulmonary hypertension. To determine whether similar peripheral airways defects occur in a common animal model of pulmonary hypertension, pulmonary function tests were performed in adult male rats rendered pulmonary hypertensive with a single subcutaneous injection of monocrotaline. At 20 days post treatment, animals exhibited well-developed right ventricular hypertrophy coincident with significant changes in lung volumes, pulmonary mechanics, and gas exchange function indicative of a severe combined restrictive and obstructive airways disorder. Morphologic changes in alveolar integrity compatible with such a pulmonary defect also were observed in monocrotaline-treated animals. The specific changes in pulmonary function observed in monocrotaline-treated rats were qualitatively similar to abnormalities reported in patients with idiopathic pulmonary hypertension. These results demonstrate that significant pulmonary mechanical, ventilatory, and gas exchange dysfunction is present in rats with monocrotaline-induced pulmonary hypertension and highlight the suitability of this model for investigating a potential contributory role of pulmonary function abnormalities in the pathogenesis of this disorder.
近期的临床研究表明，外周气道功能障碍在特发性肺动脉高压的发病机制中起作用。为确定在常见的肺动脉高压动物模型中是否会出现类似的外周气道缺陷，对成年雄性大鼠进行单次皮下注射野百合碱使其形成肺动脉高压，然后进行肺功能测试。治疗后20天，动物出现明显的右心室肥大，同时肺容量、肺力学和气体交换功能发生显著变化，提示存在严重的限制性和阻塞性气道联合疾病。在接受野百合碱治疗的动物中也观察到与这种肺部缺陷相符的肺泡完整性形态学变化。在接受野百合碱治疗的大鼠中观察到的肺功能特定变化在性质上与特发性肺动脉高压患者报告的异常相似。这些结果表明，野百合碱诱导的肺动脉高压大鼠存在明显的肺力学、通气和气体交换功能障碍，并突出了该模型在研究肺功能异常在该疾病发病机制中潜在作用的适用性。
