Dan Wang, Siqi Hu, Jingke Cao, Haoqin Fan, Ye Ma, Fan Yang, Changgen Liu, Shanghong Tang, Zhichun Feng, Yunbin Xiao, Qiuping Li
Affiliated Children’s Hospital of Xiangya School of Medicine and Central South University (Hunan Children’s Hospital). Seventh Medical Center of PLA General Hospital. Second School of Clinical Medicine and Southern Medical University. Shenzhen Baoan Women’s and Children’s Hospital.
China
Intensive Care Medicine Experimental
Int Care Med Exp 2025; 13:
DOI: 10.1186/s40635-025-00822-z
Abstract
Background: Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) seriously threatens the lives of preterm infants. The absence of animal models that can simulate its progression from early hyperoxic lung injury to late hypoxic vascular remodeling has hindered related research.
Objective: To establish a neonatal rat BPD-PH model by simulating exposure to sequential hyperoxic hypoxia experienced by human preterm infants.
Methods: Newborn SD rats were randomized into two control groups (C1 exposed to 21% O₂ for 2 weeks; C2 exposed to 21% O₂ for 3 weeks), and three exposure groups (H1 exposed to 75% O₂ for 2 weeks; H2 exposed to 75% O₂ for 2 weeks and then to 10% O₂ for a week; H3 exposed to 75% O₂ for 2 weeks and then to normoxia for a week). Cardiopulmonary parameters were evaluated by echocardiography, right ventricular systolic pressure measurement, histology, and α-SMA immunofluorescence.
Results: H1 and H2 groups exhibited distinct phenotypes, with those in the H2 group showing more severe phenotypes. The H2 group exhibited a 142% increase in RVSP relative to those in the C2 group. The right-heart index (RI) was 0.43 ± 0.01 in the H2 group, 0.36 ± 0.02 in the H3 group, and 0.22 ± 0.03 in the C2 group. Pulmonary vascular remodeling was significantly increased in the H2 group compared to the control and H3 groups. The H2 group uniquely replicated the disease process, with alveolar simplification preceding hypoxia-induced vascular thickening.
Conclusion: The sequential hyperoxic hypoxia model dynamically mimicked the clinical progression of BPD-PH, which may provide a powerful platform for stage-specific mechanism research and development of novel therapeutic strategies.
Category
Class III. Pulmonary Hypertension Associated with Lung Disease
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Animal Models of Pulmonary Vascular Disease and Therapy
Pulmonary Vascular Pathology
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes