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


RESULTS
Rats were exposed to CIH (nadir O2, 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/dtmax (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 microm/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.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland, 685 West Baltimore Street, MSTF 800, Baltimore, MD, USA.
Ling
L
Chen
Elliot
E
Einbinder
Qi
Q
Zhang
Jeffrey
J
Hasday
C William
CW
Balke
Steven M
SM
Scharf
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D006439:Hemodynamics; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008054:Lipid Peroxides / Q000032:analysis; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D013482:Superoxide Dismutase / Q000097:blood; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology*
D008054:Lipid Peroxides; D013482:Superoxide Dismutase