Phenotypic assessment of pulmonary hypertension using high-resolution echocardiography is feasible in neonatal mice with experimental bronchopulmonary dysplasia and pulmonary hypertension: a step toward preventing chronic obstructive pulmonary disease.
Phenotypic assessment of pulmonary hypertension using high-resolution echocardiography is feasible in neonatal mice with experimental bronchopulmonary dysplasia and pulmonary hypertension: a step toward preventing chronic obstructive pulmonary disease.
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DOI：
10.2147/copd.s109510
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发表时间：
2016
影响因子：
2.8
通讯作者：
Shivanna B
中科院分区：
文献类型：
--
作者：
Reynolds CL;Zhang S;Shrestha AK;Barrios R;Shivanna B
支气管肺发育不良（BPD）和慢性阻塞性肺疾病（COPD）分别是人类婴儿和成人的慢性肺部疾病，其特征是肺泡简化。三分之一的重度BPD患儿发展为肺动脉高压（PH）。更重要的是，PH增加了BPD患者的发病率和死亡率。此外，COPD是前BPD患者常见的呼吸系统疾病。缺乏适当的小动物模型，超声心动图（Echo）可以显示PH，这是了解该疾病分子机制的主要障碍之一，因此，开发合理的治疗方法来预防和/或治疗BPD患者的PH。因此，本研究的目的是建立实验性BPD和PH模型，探讨回声诊断新生小鼠PH的可行性。由于高氧诱导的氧化应激和炎症有助于BPD伴PH的发展，我们验证了新生C57BL/6J小鼠暴露于70% O2（高氧）环境14天导致肺部氧化应激、炎症、肺泡和肺血管简化、肺血管重塑、高氧暴露引起肺部氧化应激和炎症，分别通过丙二醛加合物和诱导型一氧化氮合酶的增加来证明。此外，高氧暴露导致生长受限、肺泡和肺血管简化以及肺血管重塑。在14日龄时，这些小鼠的Echo显示高氧暴露降低了肺加速时间（PAT）和PAT/射血时间比，增加了右心室自由壁厚度，这是显著PH的指标。因此，我们已经证明了Echo对实验性BPD伴PH新生小鼠PH表型的可行性，这有助于发现预防和/或治疗BPD伴PH及其后遗症如人类COPD的治疗方法。
Bronchopulmonary dysplasia (BPD) and chronic obstructive pulmonary disease (COPD) are chronic lung diseases of human infants and adults, respectively, that are characterized by alveolar simplification. One-third of the infants with severe BPD develop pulmonary hypertension (PH). More importantly, PH increases morbidity and mortality in BPD patients. Additionally, COPD is a common respiratory morbidity in former BPD patients. The lack of an appropriate small animal model wherein echocardiography (Echo) can demonstrate PH is one of the major barriers to understand the molecular mechanisms of the disease and, thereby, develop rational therapies to prevent and/or treat PH in BPD patients. Thus, the goal of this study was to establish a model of experimental BPD and PH and investigate the feasibility of Echo to diagnose PH in neonatal mice. Since hyperoxia-induced oxidative stress and inflammation contributes to the development of BPD with PH, we tested the hypothesis that exposure of newborn C57BL/6J mice to 70% O2 (hyperoxia) for 14 days leads to lung oxidative stress, inflammation, alveolar and pulmonary vascular simplification, pulmonary vascular remodeling, and Echo evidence of PH. Hyperoxia exposure caused lung oxidative stress and inflammation as evident by increased malondialdehyde adducts and inducible nitric oxide synthase, respectively. Additionally, hyperoxia exposure caused growth restriction, alveolar and pulmonary vascular simplification, and pulmonary vascular remodeling. At 14 days of age, Echo of these mice demonstrated that hyperoxia exposure decreased pulmonary acceleration time (PAT) and PAT/ejection time ratio and increased right ventricular free wall thickness, which are indicators of significant PH. Thus, we have demonstrated the feasibility of Echo to phenotype PH in neonatal mice with experimental BPD with PH, which can aid in discovery of therapies to prevent and/or treat BPD with PH and its sequelae such as COPD in humans.