Oxidative stress and left ventricular function with chronic intermittent hypoxia in rats

Rationale and Objectives: Obstructive sleep apnea (OSA) is associated with oxidative stress and myocardial dysfunction. We hypothesized that the chronic intermittent hypoxia (CIH) component of OSA is sufficient to lead to these adverse effects. Methods and Results: Rats were exposed to CIH (nadir O ₂, 4-5%) for 8 hours/day, 5 days/week, for 5 weeks. Results were compared with similarly handled controls (HC). Outcomes included blood pressure (tail cuff plethysmograph), echocardiographic and invasive measures of left-ventricular (LV) function, and indices of oxidative stress that included levels of myocardial lipid peroxides and Cu/Zn superoxide dismutase. Blood pressure was greater in CIH (n = 22) than in HC (n = 22) after 2 weeks of exposure (136 ± 12 vs. 128 ± 8 mm Hg; p < 0.05). However, the difference disappeared by 5 weeks (127 ± 13 vs. 127 ± 13 mm Hg). LV weight/heart weight was greater with CIH (CIH, 0.52 ± 0.05; HC, 0.47 ± 0.06; p < 0.005). Echocardiograms revealed LV dilation, as well as decreased LV fractional shortening (CIH, 29.7 ± 9.8%; HC, 37.4 ± 7.1%; p < 0.001). LV end-diastolic pressure was increased with CIH (CIH, 13.7 ± 5.5; HC, 8.0 ± 2.9 mm Hg; p < 0.001), decreased LV dp/dt_max, (CIH, 5072 ± 2191; HC, 6596 ± 720 mm Hg/second; p < 0.039), and decreased cardiac output (CIH, 48.2 ± 10.5; HC, 64.1 ± 10.9 ml/minute; p < 0.001). LV myocardial lipid peroxides were greater (CIH, 1,258 ± 703; HC 715 ± 240 μm/mg protein; p < 0.05) and LV myocardial superoxide dismutase levels were lower (CIH, 10.3 ± 4.9; HC, 18.6 ± 8.2 U/mg protein; p < 0.05) with CIH. Conclusions: CIH leads to oxidative stress and LV myocardial dysfunction.