Chronic hypoxia induces nonreversible right ventricle dysfunction and dysplasia in rats

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.