Oxidative stress and left ventricular function with chronic intermittent hypoxia in rats
Oxidative stress and left ventricular function with chronic intermittent hypoxia in rats
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DOI：
10.1164/rccm.200504-560oc
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发表时间：
2005-10-01
影响因子：
24.7
通讯作者：
Scharf, SM
中科院分区：
文献类型：
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作者：
Chen, L;Einbinder, E;Scharf, SM
理论基础和目的：阻塞性睡眠呼吸暂停(OSA)与氧化应激和心肌功能障碍有关。我们假设OSA的慢性间歇性低氧(CIH)成分足以导致这些不良反应。方法和结果：大鼠暴露于CIH(低氧，4-5%)中，每天8小时，每周5天，共5周。将结果与处理相似的对照组(HC)进行比较。结果包括血压(尾袖体积描记器)、超声心动图和左心室(LV)功能的有创测量，以及氧化应激指数(包括心肌过氧化脂质和铜/锌超氧化物歧化酶水平)。暴露2周后，CIH组(n=22)的血压高于对照组(n=22)(136+/-12vs.128+/-8 mm Hg；p<；0.05)。然而，这种差异在5周后消失(127+/-13对127 13 mm Hg)。脑出血组的左/心重量大于对照组(P<0.005)。超声心动图显示左室扩大，左室短轴缩短率降低(CIH，29.7+/-9.8%；HC，37.4+/-7.1%；P<；0.001)。心肌梗死后左室舒张末压升高(CIH13.7±-5.5；Hc8.0+/-2.9 mm Hg；p<；0.001)，LV dp/dt(Max)降低(CIH5072+/-2191；Hc6596+/-720 mm Hg/s；p<；0.039)，心输出量减少(CIH，48.22+/-10.5；Hc64.1+/-10.9ml/min；p<；0.001)。心肌超氧化物歧化酶水平较低(CIH，10.3+/-4.9；HC，18.6+/-8.2U/mg蛋白；P<；0.05)。
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 mu m/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.