Chronic hypoxia induces nonreversible right ventricle dysfunction and dysplasia in rats

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Abstract
The purpose of this study was to evaluate the reversibility of right ventricular (RV) remodelling after pulmonary artery hypertension (PAHT) secondary to 3 wk of hypobaric hypoxia. A group of 10 adult male Wistar rats were studied and were the following: control normoxic (C), after 3 wk of chronic hypoxia (CH), and after 3 wk of exposure to hypoxia followed by 3 wk of normoxia recovery (N-RE). Mean pulmonary artery pressure was 11 ± 2 mmHg in the C group, 35 ± 2 mmHg in the CH group, and 14 ± 3 mmHg in the N-RE group. RV function was assessed by echocardiography. In the CH group, the pulmonary flow measured in Doppler mode depicted a midsystolic notch and a decrease of the pulmonary acceleration time compared with control [17 ± 1 vs. 34 ± 1 ms ( n = 10), respectively; P < 0.05]. RV thickening measured in M-mode was apparent in the CH group compared with the control group [2.84 ± 0.40 vs. 1.73 ± 0.26 mm ( n = 10), P < 0.05]. In the N-RE group, the RV wall was significantly thinner compared with the CH group [1.56 ± 0.08 vs. 1.73 ± 0.26 mm ( n = 10), P < 0.05]. The calculated RV diameter shortness fraction was not different between the CH group and C group (34 ± 4.2% vs. 36 ± 2.8%) but decreased in the N-RE group [20 ± 2.4% ( n = 10), P < 0.01]. The E-to-A wave ratio on the tricuspid Doppler inflow was significantly lower in the CH group and N-RE group compared with the C group [0.70 ± 0.8 and 0.72 ± 0.1 vs. 0.88 ± 0.2 ( n = 10), respectively; P < 0.05]. In the isolated perfused heart using the Langendorff method, RV compliance was increased in the CH group and decreased in the N-RE group. In the N-RE group, fibrous bands with metaplasia were observed on histological sections of the RV free wall. We conclude that PAHT induces nonreversible RV dysfunction with dysplasia.

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