Mosher M, Hurst T S, Mayers I, Johnson D H
Department of Surgery, University of Saskatchewan, Saskatoon, Canada.
J Burn Care Rehabil. 1996 Jul-Aug;17(4):294-301. doi: 10.1097/00004630-199607000-00003.
Our objective was to study the effects of a lipid peroxidation inhibitor (U74389G) and nitric oxide synthetase inhibitor (NG-methyl-L-arginine) on hemodynamic stability in burn shock. The design was a prospective, placebo control, randomized, and masked multigroup study in a research laboratory of a university hospital. We used 24 guinea pigs (N = 24), and induced burn shock by a scalding thermal injury (75 degrees C) to 35% of their body surface area. Hemodynamics and gas exchange were observed for 90 minutes after the burn injury in the four groups: no burn, burn-control, burn-U74 (10 mg/kg U74389G), and burn-LNMA (20 mg/Kg NG-methyl-L-arginine). The percentage of mean arterial pressure, normalized for the initial value at 30 minutes after the burn injury, decreased in all groups over time but was not significantly different in any group. The normalized percentage of flow also decreased over time in all groups with the slope of the linear regression significantly less in the burn-U74 group (-0.32 95% CI, -0.05, -0.15) and the no burn group (-0.37 95% CI, -0.48, -0.26), compared with the burn-control group (-0.66 95% CI, -0.77, -0.56) and the burn-LNMA group (-0.66 95% CI, -0.77, -0.56). The slope of the linear regression for the normalized percentage of systemic vascular resistance was significantly more marked in the burn-control group (2.45 95% CI, 1.35, 3.54) and the burn-LNMA group (1.22 95% CI, 0.89, 1.55) compared with the no burn group (0.16 95% CI, 0.11, 0.44) or the burn-U74 group (0.34 95% CI, 0.06, 0.74). The burn shock resulted in hemodynamic instability as measured with increased systemic vascular resistance, decreased cardiac output, and mean arterial pressure. Use of a lazaroid (U74389G), not a nitric oxide synthetase inhibitor (NG-methyl-L-arginine), altered the clinical course after thermal injury. These data suggest the importance of lipid peroxidation and free radicals as secondary mediators in the evolution of burn shock.
我们的目的是研究脂质过氧化抑制剂（U74389G）和一氧化氮合酶抑制剂（NG-甲基-L-精氨酸）对烧伤休克血流动力学稳定性的影响。本研究为前瞻性、安慰剂对照、随机、双盲多组研究，在一所大学医院的研究实验室进行。我们使用了24只豚鼠（N = 24），通过75摄氏度的烫伤热损伤使其35%的体表面积烧伤，从而诱导烧伤休克。在烧伤损伤后的90分钟内，对四组进行血流动力学和气体交换观察：未烧伤组、烧伤对照组、烧伤-U74组（10mg/kg U74389G）和烧伤-LNMA组（20mg/kg NG-甲基-L-精氨酸）。烧伤损伤后30分钟时，以初始值为标准进行标准化的平均动脉压百分比，在所有组中均随时间下降，但各组间无显著差异。所有组中，标准化血流百分比也随时间下降，与烧伤对照组（-0.66 95%可信区间，-0.77，-0.56）和烧伤-LNMA组（-0.66 95%可信区间，-0.77，-0.56）相比，烧伤-U74组（-0.32 95%可信区间，-0.05，-0.15）和未烧伤组（-0.37 95%可信区间，-0.48，-0.26）线性回归斜率明显较小。与未烧伤组（0.16 95%可信区间，0.11，0.44）或烧伤-U74组（0.34 95%可信区间，0.06，0.74）相比，烧伤对照组（2.45 95%可信区间，1.35，3.54）和烧伤-LNMA组（1.22 95%可信区间，0.89，1.55）中，标准化全身血管阻力百分比的线性回归斜率明显更显著。烧伤休克导致血流动力学不稳定，表现为全身血管阻力增加、心输出量减少和平均动脉压降低。使用拉扎罗类药物（U74389G）而非一氧化氮合酶抑制剂（NG-甲基-L-精氨酸）改变了热损伤后的临床病程。这些数据表明脂质过氧化和自由基作为烧伤休克进展中的继发性介质的重要性。
