Laughlin M H, Smyk-Randall E M, Novotny M J, Brown O R, Adams H R
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, Columbia, MO.
Circ Shock. 1988 Jul;25(3):173-85.
The purposes of this study were to determine the effects of E. coli endotoxin shock on coronary blood flow (CBF) and myocardial adenine nucleotides and to determine if reactive oxygen species are major causal factors in these effects of endotoxin. Twenty-three pentobarbital-anesthetized Beagle dogs were instrumented for recording cardiorespiratory parameters, injected i.v. with saline (time-matched controls; n = 6) or endotoxin (1.5 mg/kg; n = 17), and studied for 4 h. Endotoxin dogs also received either i.v. saline (shock controls; n = 6) or i.v. treatment with either deferoxamine (30 mg/kg; n = 5) or triple therapy (n = 6) with a combination of allopurinol (150 mg/kg), superoxide dismutase (SOD) (5 mg/kg), and catalase (CAT) (5 mg/kg). Cardiorespiratory and tissue blood flow variables were constant in sham-shock controls during the study, whereas endotoxin dogs developed typical canine endotoxemia with decreased left ventricular (LV) function. CBF was decreased by approximately 40% (P less than or equal to 0.5) in all endotoxin groups throughout the 4 h study period. However, based on hemodynamic estimates of myocardial O2 demand and endocardial/epicardial blood flow ratios, it seemed that coronary flow was matched to metabolic rate in all endotoxin groups. Endotoxin significantly lowered LV myocardial concentrations of ADP, AMP, NADH, and NADPH (range = 37 to 54%, P less than or equal to 0.05), but ATP, NAD, and NADP concentrations were not changed. The adenylate charge of the myocardium was between 0.91 and 0.95 in all endotoxin groups, suggesting that adequate energy was available in the myocardium during endotoxin shock. The lack of influence of deferoxamine, allopurinol, SOD, and CAT is indirect evidence that oxygen radicals are not primary pathophysiologic mediators in the cardiac response to gram-negative endotoxemia in this endotoxin model.
本研究的目的是确定大肠杆菌内毒素休克对冠状动脉血流量（CBF）和心肌腺嘌呤核苷酸的影响，并确定活性氧是否是内毒素这些作用的主要因果因素。23只戊巴比妥麻醉的比格犬被安装仪器记录心肺参数，静脉注射生理盐水（时间匹配对照组；n = 6）或内毒素（1.5 mg/kg；n = 17），并研究4小时。内毒素组犬还静脉注射生理盐水（休克对照组；n = 6）或静脉注射去铁胺（30 mg/kg；n = 5）或三联疗法（n = 6），三联疗法使用别嘌呤醇（150 mg/kg）、超氧化物歧化酶（SOD）（5 mg/kg）和过氧化氢酶（CAT）（5 mg/kg）的组合。在研究期间，假休克对照组的心肺和组织血流变量保持恒定，而内毒素组犬出现典型的犬内毒素血症，左心室（LV）功能下降。在整个4小时的研究期间，所有内毒素组的CBF均降低了约40%（P≤0.5）。然而，根据心肌氧需求的血流动力学估计和心内膜/心外膜血流比值，似乎所有内毒素组的冠状动脉血流与代谢率相匹配。内毒素显著降低LV心肌中ADP、AMP、NADH和NADPH的浓度（范围为37%至54%，P≤0.05），但ATP、NAD和NADP的浓度未改变。所有内毒素组心肌的腺苷酸电荷在0.91至0.95之间，表明在内毒素休克期间心肌中有足够的能量可用。去铁胺、别嘌呤醇、SOD和CAT缺乏影响是间接证据，表明在该内毒素模型中，氧自由基不是心脏对革兰氏阴性内毒素血症反应的主要病理生理介质。
