Fahey T J, Yoshioka T, Shires G T, Fantini G A
Department of Surgery, New York Hospital-Cornell Medical Center, New York, USA.
Ann Surg. 1996 Jan;223(1):63-9. doi: 10.1097/00000658-199601000-00009.
This study was designed to examine the differential effects of tumor necrosis factor (TNF) and nitric oxide on the acute cardiovascular changes that occur in response to endotoxemia.
Recent studies have suggested that some, if not all, of the cardiovascular effects of TNF are mediated through release of nitric oxide. However, the mechanisms through which TNF and nitric oxide induce hypotension and shock in vivo in response to systemic endotoxemia remain poorly characterized, despite current interest in the use of nitric oxide antagonists to ameliorate septic shock.
A reproducible model of endotoxemia was established in adult Sprague-Dawley rats. The acute cardiovascular changes that occur after bolus infusion of endotoxin was then determined in rats treated with either TNF antibody, N-methyl arginine, or both.
Inhibition of either TNF or nitric oxide restores mean arterial blood pressure to normal after endotoxemia (p < 0.05). However, nitric oxide exerts its effects principally on the peripheral vasculature, whereas TNF appears to act on the myocardium. A combination of TNF antiserum pretreatment and N-methyl arginine administration is necessary to return mean arterial blood pressure to normal 60 minutes after endotoxin infusion.
Tumor necrosis factor and nitric oxide mediate the acute cardiovascular effects of endotoxemia through distinct mechanisms. Nitric oxide is released as a result of both TNF-dependent and TNF-independent mechanisms, whereas the cardiovascular effects of TNF are only partially mediated through nitric oxide.
本研究旨在探讨肿瘤坏死因子（TNF）和一氧化氮对内毒素血症时发生的急性心血管变化的不同影响。
最近的研究表明，TNF的某些（如果不是全部）心血管作用是通过一氧化氮的释放介导的。然而，尽管目前对使用一氧化氮拮抗剂改善脓毒性休克感兴趣，但TNF和一氧化氮在体内因全身内毒素血症诱导低血压和休克的机制仍未得到充分描述。
在成年Sprague-Dawley大鼠中建立可重复的内毒素血症模型。然后在接受TNF抗体、N-甲基精氨酸或两者治疗的大鼠中确定内毒素推注后发生的急性心血管变化。
在内毒素血症后，抑制TNF或一氧化氮均可使平均动脉血压恢复正常（p<0.05）。然而，一氧化氮主要对外周血管系统起作用，而TNF似乎作用于心肌。在内毒素输注60分钟后，需要联合使用TNF抗血清预处理和N-甲基精氨酸给药才能使平均动脉血压恢复正常。
肿瘤坏死因子和一氧化氮通过不同机制介导内毒素血症的急性心血管作用。一氧化氮通过TNF依赖性和TNF非依赖性机制释放，而TNF的心血管作用仅部分通过一氧化氮介导。
