Metabolic profiling of arginine and nitric oxide pathways predicts hemodynamic abnormalities and mortality in patients with cardiogenic shock after acute myocardial infarction
Metabolic profiling of arginine and nitric oxide pathways predicts hemodynamic abnormalities and mortality in patients with cardiogenic shock after acute myocardial infarction
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DOI：
10.1161/circulationaha.107.693986
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发表时间：
2007-11-13
期刊：
影响因子：
37.8
通讯作者：
Hazen, Stanley L.
中科院分区：
文献类型：
--
作者：
Nicholls, Stephen J.;Wang, Zeneng;Hazen, Stanley L.
背景-精氨酸和一氧化氮代谢异常是否与急性心肌梗死后心源性休克(CS)患者的血流动力学功能障碍和死亡率有关尚不清楚。方法和结果：对79例心源性休克(CS)患者和79例年龄和性别匹配的冠心病和左心功能正常的患者进行了反映精氨酸生物利用度、一氧化氮代谢和蛋白质氧化的质谱分析。CS患者血浆不对称性二甲基精氨酸(ADMA；P<；0.0001)、对称性二甲基精氨酸(P<；0.0001)、单甲基精氨酸(P=0.0003)、硝基酪氨酸(P<；0.0001)和溴酪氨酸(P<；0.0001)水平较高，精氨酸(P<；0.0001)、精氨酸/鸟氨酸和瓜氨酸(P<；0.0001)比值较低(P=0.0003)。ADMA水平升高的CS患者30天内死亡的可能性是ADMA水平低的患者的3.5倍(95%可信区间，1.4至11.3；P=0.02)。在多因素Logistic回归分析中，ADMA仍然是死亡率的唯一独立预测因素。在肾功能正常的患者中，对称性二甲基精氨酸水平与平均动脉压和全身血管阻力呈负相关，而ADMA水平与肺毛细血管楔压、肺动脉收缩压和舒张压呈正相关。尽管蛋白质氧化产物水平显著升高，但并不能预测CS患者的血流动力学功能障碍或死亡率。结论CS患者的特点是精氨酸缺乏，具有高度特异性的促氧化状态，甲基化的精氨酸衍生物水平升高，包括内源性一氧化氮合酶抑制物。甲基化精氨酸衍生物水平与血流动力学功能障碍密切相关。在所有监测的临床和实验室参数中，ADMA水平是30天死亡率的最强独立预测因子。
Background-It is unclear whether abnormalities of arginine and nitric oxide metabolism are related to hemodynamic dysfunction and mortality in patients with cardiogenic shock (CS) after acute myocardial infarction.Methods and Results-Plasma metabolites reflecting arginine bioavailability, nitric oxide metabolism, and protein oxidation were analyzed by mass spectrometry in patients with CS (n = 79) and age- and gender- matched patients with coronary artery disease and normal left ventricular function (n = 79). CS patients had higher levels of asymmetric dimethylarginine (ADMA; P < 0.0001), symmetric dimethylarginine (P < 0.0001), monomethylarginine (P = 0.0003), nitrotyrosine (P < 0.0001), and bromotyrosine (P < 0.0001) and lower levels of arginine (P < 0.0001), ratio of arginine to ornithine (P = 0.03), and ratio of arginine to ornithine plus citrulline) (P = 0.0003). CS patients with elevated ADMA levels were 3.5- fold (95% confidence interval, 1.4 to 11.3; P = 0.02) more likely to die in 30 days than patients with low ADMA levels. ADMA remained the only independent predictor of mortality on multiple logistic regression analysis. In patients with normal renal function, symmetric dimethylarginine levels inversely correlated with mean arterial pressure and systemic vascular resistance, whereas levels of ADMA correlated with pulmonary capillary wedge pressure and both systolic and diastolic pulmonary artery pressures. Despite dramatic elevations, levels of protein oxidation products did not predict hemodynamic dysfunction or mortality in CS patients.Conclusions-CS is characterized by an arginine- deficient and highly specific pro- oxidant state, with elevated levels of methylated arginine derivatives, including endogenous nitric oxide synthase inhibitors. Levels of methylated arginine derivatives strongly correlate with hemodynamic dysfunction. Among all clinical and laboratory parameters monitored, ADMA levels were the strongest independent predictor of 30- day mortality.