Left Ventricular Dysfunction and Associated Cellular Injury in Rats exposed to Chronic Intermittent Hypoxia Running Head: Cardiac Injury in Intermittent Hypoxia

ABSTRACT Background: Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality. We have reported that chronic intermittent hypoxia (CIH), a direct consequence during OSA, leads to left ventricular (LV) remodeling and dysfunction in rats. The present study is to determine LV myocardial cellular injury that is possibly associated with LV global dysfunction. Methods: Fifty-six rats were exposed either to CIH (nadir O 2 4-5%) or sham (handled normoxic controls, HC), 8 hours per day for 6 weeks. At the end of the exposure, we studied LV global function by cardiac catheterization, and LV myocardial cellular injury by in vitro analyses. Results: Compared to HC, CIH animals demonstrated elevations in mean arterial pressure and LV end-diastolic pressure, but reductions in cardiac output (CIH: 141.3±33.1 vs. HC 184.4±21.2 ml/min/kg, p<0.01), LV maximal positive d P /dt, and maximal negative d P /dt. CIH led to significant cell injury in the left myocardium, including elevated LV myocyte size, measured by cell surface area (CIH 3564±354