Bone H G, Waurick R, Van Aken H, Booke M, Prien T, Meyer J
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Münster, Germany.
Intensive Care Med. 1998 Jan;24(1):48-54. doi: 10.1007/s001340050514.
The present study compared the effects of nitric oxide (NO) synthase inhibition and NO scavenging with haemoglobin in endotoxaemic sheep.
12 sheep were instrumented for chronic study. Six sheep received LG-nitro-arginine-methylester (L-NAME, 2.5 mg/kg bolus followed by a continuous infusion of 0.5 mg/kg per h), the other 6 sheep received pyridoxalated haemoglobin polyoxyethylene conjugate (PHP, 100 mg/kg bolus followed by a continuous infusion of 20 mg/kg per h).
Haemodynamic and oxygenation parameters were measured in healthy sheep, after infusion of Salmonella typhosa endotoxin (10 ng/kg per min) for 24 h and after infusion of L-NAME or PHP. The infusion of endotoxin resulted in a hypotensive, hyperdynamic circulation. Infusion of L-NAME increased mean arterial pressure (MAP) from 76.1 +/- 4.2 mmHg to normal values of 95.8 +/- 5.7 mmHg (p < 0.05). PHP increased MAP from 73.0 +/- 3.0 to 88.6 +/- 4.7 mmHg (p < 0.05). This increase in MAP was associated in the L-NAME group with a more prominent drop in cardiac index (from 10.2 +/- 0.4 to 7.0 +/- 0.51.min-1.m-2; p < 0.05) than in the PHP group (from 10.7 +/- 0.2 to 9.3 +/- 0.61.min-1.m-2). During the first 90 min of infusion, cardiac index remained lower in the L-NAME group than in the PHP group. The increase in pulmonary vascular resistance was also higher in the L-NAME group.
These results suggest, that at the doses used in the experiment, NO scavenging with PHP has smaller effects on cardiac index and pulmonary vascular resistance than NO synthase inhibition with L-NAME. Therefore, the concept of NO scavenging in hyperdynamic sepsis should be further evaluated.
本研究比较了一氧化氮（NO）合酶抑制和用血红蛋白清除内毒素血症绵羊体内NO的效果。
12只绵羊安装仪器用于长期研究。6只绵羊接受左旋硝基精氨酸甲酯（L-NAME，2.5mg/kg静脉推注，随后以0.5mg/kg每小时持续输注），另外6只绵羊接受吡哆醛化血红蛋白聚氧乙烯共轭物（PHP，100mg/kg静脉推注，随后以20mg/kg每小时持续输注）。
在健康绵羊中、输注鼠伤寒沙门氏菌内毒素（10ng/kg每分钟）24小时后以及输注L-NAME或PHP后测量血流动力学和氧合参数。输注内毒素导致低血压、高动力循环。输注L-NAME使平均动脉压（MAP）从76.1±4.2mmHg升高至正常水平95.8±5.7mmHg（p<0.05）。PHP使MAP从73.0±3.0升高至88.6±4.7mmHg（p<0.05）。L-NAME组MAP的这种升高与心脏指数更显著下降（从10.2±0.4降至7.0±0.51.min-1.m-2；p<0.05）相关，比PHP组（从10.7±0.2降至9.3±0.61.min-1.m-2）更明显。在输注的前90分钟内，L-NAME组的心脏指数仍低于PHP组。L-NAME组肺血管阻力的增加也更高。
这些结果表明，在实验所用剂量下，与用L-NAME抑制NO合酶相比，用PHP清除NO对心脏指数和肺血管阻力的影响较小。因此，在高动力性脓毒症中清除NO的概念应进一步评估。
