Research on rat models of hypobaric hypoxia-induced pulmonary hypertension

T.-T. Ma, Y. Wang, X.-L. Zhou, H. Jiang, R. Guo, L.-N. Jia, H. Chang, Y. Gao, X.-Y. Yao, Z.-M. Gao, L. Pan

Department of Geriatric Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China. leipan61@aliyun.com

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• Cardiology

OBJECTIVE: Rat models of hypobaric hypoxia-induced pulmonary hypertension are commonly used in studies of chronic mountain sickness, while there are few researches specially focusing on these rats model. This study aims to exploring possible pathogenesis of hypobaric hypoxia-induced pulmonary hypertension by experimenting on hypobaric hypoxia-induced PH rat models at different simulate-altitudes.

MATERIALS AND METHODS: 32 healthy male SD rats were randomly divided into six groups of different degree and time period of hypobaric hypoxia. The mean pulmonary arterial pressure (m PAP), right ventricular pressure (RVSP), the right ventricle (RV), left ventricular (LV), ventricular septal (S), the right ventricular hypertrophy index (RVHI) [calculated under the formula of RV / (LV + S)], hematoxylin-eosin staining, elastic fibers staining, the ratio of the thickness of vascular wall to its outer diameter (MT%), the ratio of the cross-sectional area of the middle vascular wall to the total vascular cross-sectional area (MA%); the α-SMA, and the Ki6 expressions were detected to evaluated the pulmonary hypertension.

RESULTS: There were significant differences of the mPAP, RVSP and RVHI value between the hypobaric hypoxia groups and the control group (p < 0.05). The mPAP, RVSP, RVHI, MT%, MA%, α-SMA, and Ki6 of rats in model groups at an altitude of 3KM were higher than those of the control group, which raised gradually with the number of weeks increasing. The mPAP, RVSP, RV / (LV + S) value, MT%, MA%, α-SMA, and Ki67 of the 5KM-4W group were significantly higher than those of the control group (p < 0.05).

CONCLUSIONS: Rat models with pulmonary hypertension at different altitudes have been successfully established by automatic adjusting hypobaric hypoxia chamber. Exposure to a low oxygen environment at a simulate-altitude of 3 km for 8 weeks have caused the pathological remodeling of pulmonary vascular walls and pulmonary hypertension, and further led to a series of pathological changes, including right ventricular hypertrophy. This model is easy to be replicated with good reproducibility and provides evidence for clinical trial of drugs.

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