Study Objective: No studies have investigated sequential changes in the heart on magnetic resonance imaging (MRI), along with observation of functional lung phenotypes and genetics, over the duration of chronic intermittent hypoxia (CIH). We investigated chronological changes in heart and lung phenotypes after CIH using a mouse model to provide new insights into the pathophysiology of sleep apnea-induced cardiovascular disease. Methods: C57BL/6J adult male mice were randomized to 4 or 8 weeks of CIH. Cardiac cine-MRI images were analyzed to assess functional parameters of right ventricle (RV). Histopathological features of myocytes and pulmonary vessels, as well as genes involved in the endothelin (ET) system, were investigated. Results: Function of the RV reduced significantly at 4 weeks and continuously decreased following another 4 weeks of CIH, although the rate of decrease was attenuated. Notably, persistence of reduced ejection fraction and end-systole RV wall thickness (WT) and increases in the ET system of the lungs and blood strongly implied the development of pulmonary hypertension after 8 weeks of CIH. Conclusions: RV dysfunction with reduced end-systole RV WT could be a late phenotype in long-standing CIH and possibly also in obstructive sleep apnea.
Bibliographical noteFunding Information:
This research was supported by grants 2015R1D1A1A02062228 to C. H. Kim, NRF-2013R1A1A 1010151 and 2015R1D1A1A02062156 to H. J. Cho, NRF-2011–002945 to J. Y. Kim, and 2013R1A3A2042197 to M. G. Lee from the National Research Foundation of Korea (NRF), funded by the Ministry of Education and the Ministry of Science, ICT & Future Planning through, Korea. This research was also supported (in part) by the Yonsei University Future-leading Research Initiative of 2014 (2014-22-0131) to C. H. Kim and a faculty research grant from Yonsei University College of Medicine (6-2015-0048) to J. Y. Kim and (6-2016-0061) to H. J. Cho.
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All Science Journal Classification (ASJC) codes
- Clinical Neurology
- Physiology (medical)