Myocardial hypoxia is a major cause of cardiac dysfunction due to its triggering cell injury and apoptosis. Recently we developed a rabbit model of tracheal stenosis (TS) induced by endotracheal intubation using a segmented tracheal tube, which is based on the physiologic condition of prolonged endotracheal intubation. We aimed to evaluate the impact of sub-acute hypoxic status on the cardiac remodeling and mitochondrial oxygen consumption using TS rabbit model.Design and method:
TS was induced by inserting a segmented endotracheal tube of 1.5 cm length which was wrapped with a commercialized absorbable hemostat in 6 rabbits, while sham surgery controls (n = 3) underwent tracheotomy and direct closure of tracheal exposure. The tube was removed transorally, 1 week after tube insertion. Hearts and isolated mitochondria from TS rabbits and controls were morphologically and functionally analyzed at 3 weeks after endoscopic confirmation of TS.Results:
TS model showed significantly reduced interventricular septal wall thickness (2.3 ± 0.1 vs. 2.7 ± 0.2 mm, p = 0.08) and enlarged left ventricular (LV) end-diastolic volume (5.86 ± 0.58 vs. 5.39 ± 0.18 mL, p = 0.46) with reduced LV ejection fraction (54.5 ± 5.29 vs. 66.9 ± 3.98%, p = 0.005) and fractional shortening compared with controls. In addition, TS model showed significantly reduced mitochondrial O2 consumption at the stage 3 with reduced respiratory control ratio. On the caspase activity assay, TS model showed increased hypoxia-induced apoptosis via caspase-9 and caspase-3 apoptotic pathway.Conclusions:
Taken together, our data demonstrated that mitochondrial dependent apoptotic pathways and cardiac remodeling might be induced by hypoxia in the condition of prolonged endotracheal intubation and implicate the preventive treatment for the cardiac dysfunctions.