Schaller Georg, Pleiner Johannes, Mittermayer Friedrich, Posch Martin, Kapiotis Stylianos, Wolzt Michael
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Crit Care Med. 2007 Aug;35(8):1869-75. doi: 10.1097/01.CCM.0000275385.45557.25.
Systemic inflammation causes vasodilation and impairs the vascular response to catecholamines. There is evidence that altered vasoreactivity is associated with increased production of free radicals. We studied the influence of systemic doses of the antioxidant N-acetylcysteine on inflammatory cytokines and renal plasma flow and on the systemic pressor response to norepinephrine during experimental endotoxemia.
A double-blind, placebo-controlled crossover study.
Medical University of Vienna, Clinical Pharmacology, Vienna General Hospital, AKH.
Eight healthy, male humans.
Intravenous administration of Escherichia coli endotoxin (lipopolysaccharide, 20 IU/kg) on two separate study days with concomitant intravenous infusion of placebo or N-acetylcysteine (150 mg/kg loading dose; 15 mg/kg/hr continuous infusion), respectively.
Measurements of inflammatory cytokines, of renal plasma flow by the para-aminohippurate-clearance method, and of the systemic pressor response to norepinephrine were taken at baseline and after endotoxin. Lipopolysaccharide increased body temperature and plasma concentrations of tumor necrosis factor-alpha, which was mitigated during N-acetylcysteine infusions. Likewise, the lipopolysaccharide-induced increases in renal plasma flow and decreases in blood pressure were attenuated, and the hyporeactivity of pulse rate to norepinephrine 4 hrs after lipopolysaccharide was improved by N-acetylcysteine.
High doses of N-acetylcysteine might exert protective effects on systemic hemodynamics and on the reactivity to catecholamines in humans challenged by lipopolysaccharide. This action of the antioxidant N-acetylcysteine is paralleled by humoral anti-inflammatory mechanisms and may be useful in patients with systemic inflammation.
全身炎症可导致血管舒张，并损害血管对儿茶酚胺的反应。有证据表明血管反应性改变与自由基生成增加有关。我们研究了全身给予抗氧化剂N-乙酰半胱氨酸对内毒素血症实验期间炎症细胞因子、肾血浆流量以及对去甲肾上腺素的全身升压反应的影响。
双盲、安慰剂对照交叉研究。
维也纳医科大学临床药理学系，维也纳总医院，AKH。
八名健康男性。
在两个不同的研究日静脉注射大肠杆菌内毒素（脂多糖，20 IU/kg），同时分别静脉输注安慰剂或N-乙酰半胱氨酸（150 mg/kg负荷剂量；15 mg/kg/小时持续输注）。
在基线和注射内毒素后测量炎症细胞因子、用对氨基马尿酸清除法测量肾血浆流量以及对去甲肾上腺素的全身升压反应。脂多糖使体温和肿瘤坏死因子-α血浆浓度升高，在输注N-乙酰半胱氨酸期间这种升高得到缓解。同样，脂多糖诱导的肾血浆流量增加和血压降低也得到减轻，N-乙酰半胱氨酸改善了脂多糖注射4小时后脉搏率对去甲肾上腺素的反应性降低。
高剂量的N-乙酰半胱氨酸可能对脂多糖攻击的人体的全身血流动力学和对儿茶酚胺的反应性发挥保护作用。抗氧化剂N-乙酰半胱氨酸的这种作用与体液抗炎机制并行，可能对全身炎症患者有用。
