Subacute Hypoxia Induces Cardiac Remodeling and Mitochondrial Dysfunction via Apoptotic Pathways in a Rabbit Model of Tracheal Stenosis

Myocardial hypoxia is a major cause of cardiac dysfunction, triggering cellular injury and apoptosis. This study aims to investigate the effects of subacute hypoxia on cardiac remodeling and mitochondrial oxygen consumption. This study is based on a rabbit experimental model. Hypoxia was induced using a rabbit tracheal stenosis model. Endotracheal intubation with a 1.5 cm segmented tube wrapped with an absorbable hemostat was used to generate tracheal stenosis in six rabbits. Sham controls (<i>n</i> = 3) underwent tracheotomy, with the tracheal exposure site being sutured immediately. After 1 week, the tube was removed. Echocardiography and mitochondrial function from both groups were morphologically and functionally analyzed at 2 weeks after endoscopic confirmation of tracheal stenosis. Compared to sham group, tracheal stenosis group showed significantly reduced interventricular septal wall thickness (2.3 ± 0.1 mm vs. 2.7 ± 0.2 mm, <i>p</i> = 0.08) and enlarged left ventricular end-diastolic volume (5.86 ± 0.58 mL vs. 5.39 ± 0.18 mL, <i>p</i> = 0.46) with reduced left ventricular ejection fraction (54.5 ± 5.3% vs. 66.9 ± 4.0%, <i>p</i> = 0.005). The tracheal stenosis group showed significantly reduced mitochondrial oxygen consumption at state 3 with reduced respiratory control ratio. Caspase activities (caspase-9 and caspase-3) were increased in the tracheal stenosis group than in the sham group. Subacute hypoxia induced by the tracheal stenosis model causes cardiac remodeling and mitochondrial dysfunction through apoptotic pathways. This study suggests that management of hypoxia could prevent cellular apoptosis and cardiac dysfunction.