Cardiovascular Effects of Chronic Intermittent Hypoxia in Mice

Abstract

Obstructive sleep apnea syndrome (OSA), resulting from repetitive episodes of upper airway occlusion during sleep, increases cardiovascular mortality and morbidity. To determine suitability of mouse model for OSA, we examine the cardiovascular response to chronic intermittent hypoxia (CIH), one of major physiological changes in OSA. Methods Adult C57BL/6 mice were daily exposed to either CIH (cycles of 1-min hypoxia with nadir FIO2 5%, followed by 1-min normoxia, 10 daytime hours/day for 2 months, n=22) or similarly handled normoxic control (C, n=17). Measurements performed include body weight (BW); cardiac catheterization under 2% isoflurane anesthesia after 12 hours following the end of the last exposure; and heart wet weight after euthanasia. Results There is no significant difference between CIH and C in BW, heart rate, rate of left ventricular (LV) pressure rise (+dP/dtmax), rate of LV pressure fall (−dP/dtmax), and weight ratio of right ventricular free wall to BW. CIH increased mean arterial pressure (CIH: 92.8±11.7 vs C: 84.5±11.5 mm Hg, p=0.03), LV end-diastolic pressure (12.5±6.8 vs 5.5±5.4 mm Hg, p<0.01), heart weight to BW ratio (4.1±0.6 vs 3.6±0.3 mg/g, p<0.05), and LV free wall weight to BW ratio (2.07±0.27 vs 1.71±0.18 mg/g, p<0.01). Conclusions Mice with CIH develop higher blood pressure, LV dysfunction, and LV hypertrophy. These changes mimic cardiovascular changes in patients with OSA. We speculate that future use of genetically modified mice with CIH may be useful for investigation of the molecular mechanisms of cardiovascular change in OSA. Supported by NHLBI.