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Original Research: Sleep Disorders |

Intermittent Hypoxia-Induced Cardiovascular Remodeling Is Reversed by Normoxia in a Mouse Model of Sleep Apnea

Anabel L. Castro-Grattoni, MS; Roger Alvarez-Buvé, MS; Marta Torres, PhD; Ramon Farré, PhD; Josep M. Montserrat, MD, PhD; Mireia Dalmases, MD; Isaac Almendros, PhD; Ferran Barbé, MD, PhD; Manuel Sánchez-de-la-Torre, PhD
Author and Funding Information

FUNDING/SUPPORT: This work was supported by the Spanish Respiratory Society (SEPAR), the Associació Lleidatana de Respiratori (ALLER), and the Spanish Fondo de Investigaciones Sanitarias PI14/00004, Instituto de Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”.

CORRESPONDENCE TO: Manuel Sánchez-de-la-Torre, PhD, Hospital Arnau de Vilanova-Santa María, IRB Lleida, CIBERES, Avda Rovira Roure 80, 25198, Lleida, Spain


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(6):1400-1408. doi:10.1016/j.chest.2015.11.010
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Background  Intermittent hypoxia (IH) is the principal injurious factor involved in the cardiovascular morbidity and mortality associated with OSA. The gold standard for treatment is CPAP, which eliminates IH and appears to reduce cardiovascular risk. There is no experimental evidence on the reversibility of cardiovascular remodeling after IH withdrawal. The objective of the present study is to assess the reversibility of early cardiovascular structural remodeling induced by IH after resumption of normoxic breathing in a novel recovery animal model mimicking OSA treatment.

Methods  We investigated cardiovascular remodeling in C57BL/6 mice exposed to IH for 6 weeks vs the normoxia group and its spontaneous recovery after 6 subsequent weeks under normoxia.

Results  Aortic expansive remodeling was induced by IH, with intima-media thickening and without lumen perimeter changes. Elastic fiber network disorganization, fragmentation, and estrangement between the end points of disrupted fibers were increased by IH. Extracellular matrix turnover was altered, as visualized by collagen and mucoid interlaminar accumulation. Furthermore, left ventricular perivascular fibrosis was increased by IH, whereas cardiomyocytes size was unaffected. These cardiovascular remodeling events induced by IH were normalized after recovery in normoxia, mimicking CPAP treatment.

Conclusions  The early structural cardiovascular remodeling induced by IH was normalized after IH removal, revealing a novel recovery model for studying the effects of OSA treatment. Our findings suggest the clinical relevance of early detection and effective treatment of OSA in patients to prevent the natural course of cardiovascular diseases.

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