Novotny M J, Laughlin M H, Adams H R
Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia 65211.
Am J Physiol. 1988 May;254(5 Pt 2):H954-62. doi: 10.1152/ajpheart.1988.254.5.H954.
Reactive oxygen species have been proposed as pathophysiological factors responsible for the hypodynamic circulatory response to gram-negative endotoxin. To test this hypothesis, we examined the cardiorespiratory effects of mechanistically different oxygen free radical scavenging agents during Escherichia coli endotoxemia in beagle dogs. Pentobarbital-anesthetized dogs were instrumented for repeated sampling of cardiorespiratory, hematologic, and tissue blood flow (radiolabeled 15-micron microspheres) indexes. Four groups were studied: 1) time-matched control dogs (n = 6); 2) dogs receiving only endotoxin (1.5 mg/kg; n = 6); 3) dogs receiving endotoxin and combination therapy with allopurinol (150 mg/kg) plus superoxide dismutase (5 mg/kg) and catalase (5 mg/kg; n = 6); and 4) dogs receiving endotoxin and deferoxamine (30 mg/kg; n = 5). Measured variables in control dogs were constant during the 4-h study, whereas endotoxin-injected dogs consistently demonstrated the following: 1) maintained reductions in blood pressure (greater than 45%), left ventricular systolic pressure (greater than 43%), left ventricular maximum rate of pressure development (+/- dP/dtmax) (greater than 41%), cardiac index (greater than 33%), and blood flow in all sampled tissues except liver and skeletal muscle; 2) transient tachypnea, bradycardia, and arterial acidosis; and 3) persistent neutropenia and hemoconcentration. Neither of the free radical scavenging protocols significantly improved measured variables during endotoxemia (P greater than 0.05). This lack of efficacy suggests that superoxide anion, hydrogen peroxide, and hydroxyl radical may lack primary pathophysiological importance during the development of E. coli endotoxicosis in intact dogs.
活性氧已被认为是导致革兰氏阴性内毒素引起的循环动力不足反应的病理生理因素。为了验证这一假设，我们在比格犬的大肠杆菌内毒素血症期间，研究了机制不同的氧自由基清除剂对心肺的影响。用戊巴比妥麻醉的犬被安装了用于重复采集心肺、血液学和组织血流（放射性标记的15微米微球）指标的仪器。研究了四组：1）时间匹配的对照犬（n = 6）；2）仅接受内毒素的犬（1.5 mg/kg；n = 6）；3）接受内毒素并联合使用别嘌呤醇（150 mg/kg）加超氧化物歧化酶（5 mg/kg）和过氧化氢酶（5 mg/kg；n = 6）的犬；4）接受内毒素和去铁胺（30 mg/kg；n = 5）的犬。在4小时的研究中，对照犬的测量变量保持恒定，而注射内毒素的犬始终表现出以下情况：1）血压持续降低（大于45%）、左心室收缩压（大于43%）、左心室最大压力上升速率（+/- dP/dtmax）（大于41%）、心脏指数（大于33%），以及除肝脏和骨骼肌外所有采样组织的血流减少；2）短暂的呼吸急促、心动过缓和动脉酸中毒；3）持续的中性粒细胞减少和血液浓缩。在内毒素血症期间，两种自由基清除方案均未显著改善测量变量（P大于0.05）。这种缺乏疗效表明，在完整犬的大肠杆菌内毒素中毒发展过程中，超氧阴离子、过氧化氢和羟基自由基可能缺乏主要的病理生理重要性。
