0185 : Characterization of IH-induced cardiac remodeling and contractile dysfunction in a rat model of heart failure

Background The prevalence of obstructive sleep apnea (OSA) in heart failure (HF) patients ranges from 12 to 53% and is associated with a poor prognosis. Chronic Intermittent hypoxia (IH) is described as the most detrimental factor leading to cardiovascular morbi-mortality in OSA patients. Thus, we hypothesized that IH plays a major role in the development of postinfarction HF, notably through an accelerated development of hypertrophy and contractile dysfunction. Objectives To determine the kinetic of cardiac remodeling and contractile dysfunction in HF rats exposed to 1 to 4 weeks IH. Methods Wistar male rats underwent myocardial infarction by permanent left coronary artery ligation. Then, they were exposed to IH (21-5% FiO2, 60s cycle, 8 h/day) or normoxia (N) during 1 to 4 weeks. Echocardiography was performed before and after each week of exposure to evaluate left ventricular (LV) parameters (i.e. ejection fraction (EF), shortening fraction (SF), LV wall thickness and cavity dimensions). Arterial and LV pressures were determined by carotid and cardiac catheterization at the end of the IH or N exposure and rat hearts were used for cardiac hypertrophy analysis. Results Preliminary results showed that one week exposure to IH tends to induce increase in arterial and LV pressures. This was associated with a deterioration of LV function, characterized by a decreased EF (39.3±1.9% vs 43.0±1.7%, Day 7 vs Day 0) and SF (20.1±1.1% vs 22.2±1.0%, Day 7 vs Day 0) in IH rats, whereas LV function remains stable in the normoxic group. Modifications of LV dimensions and heart weights were similar between N and IH. On-going experiments are characterizing cardiac hypertrophy (immunohistology and mRNA analysis). Discussion Only one week exposure to IH seems to induce deterioration of LV function, which was not associated, at this time point, with cardiac remodeling. Further experiments are needed to characterize the effects of longer IH exposure (up to 4 weeks) on HF development. The author hereby declares no conflict of interest