Weingand K W, Fettman M J, Phillips R W, Hand M S
Circ Shock. 1986;19(1):55-67.
Lactic acidosis is significant in the pathophysiology of endotoxicosis. By increasing the activity of pyruvate dehydrogenase, sodium dichloroacetate (DCA) decreases lactate production and may be useful as a therapy for endotoxic shock. Five (n = 5) 50-80-kg Yucatan minipigs were fitted with jugular, portal, hepatic vein, and carotid artery catheters, and hepatic artery and portal vein flow cuffs to quantitate transhepatic kinetics of glucose, lactate, and insulin. Three days later, they were placed in slings, and a primed-continuous intravenous infusion of 3-tritiated glucose was initiated to monitor whole body glucose kinetics. Following a 3-hour control period, an intravenous infusion of E. coli endotoxin (LPS) was administered at 15 micrograms/kg/hr for 6 hours. After 1 hour of LPS infusion, DCA was administered as a primed (30 mg/kg)-continuous (30 mg/kg/hr) intravenous infusion for 5 hours. These DCA-treated endotoxemic minipigs (group DE) were compared statistically to a group (n = 8) of minipigs given endotoxin only (group E). Group DE arterial lactate concentrations eventually decreased (19.2 +/- 1.0 mg/dl) significantly (P less than or equal to 0.05) below group E (39.3 +/- 7.7 mg/dl) in the last hour of DCA infusion. The progressive hypoglycemia of group DE decreased below that of group E and became significantly (P less than or equal to 0.05) lower in the last hour of the experiment (33.6 +/- 11.5 vs 50.6 +/- 10.0 mg/dl, respectively) due to decreased hepatic gluconeogenesis as evidenced by a lower relative rate of appearance (%Ra) of glucose and decreased hepatic glucose output and lactate extraction. A large relative decrease in pancreatic output of insulin in group DE contributed to the lower serum insulin levels than group E throughout the treatment period. Lethality in group DE (60%) was unaltered from that of group E (67%). Despite its ability to decrease arterial lactate concentrations, DCA alone does not appear to be an effective treatment for endotoxicosis.
乳酸性酸中毒在内毒素血症的病理生理学中具有重要意义。通过增加丙酮酸脱氢酶的活性，二氯乙酸钠（DCA）可减少乳酸生成，可能作为内毒素休克的一种治疗方法。选用5头（n = 5）体重50 - 80千克的尤卡坦小型猪，安装颈静脉、门静脉、肝静脉和颈动脉导管，以及肝动脉和门静脉血流袖带，以定量葡萄糖、乳酸和胰岛素的肝内动力学。三天后，将它们置于吊床中，开始以初量 - 持续静脉输注3 - 氚标记葡萄糖来监测全身葡萄糖动力学。在3小时的对照期后，以15微克/千克/小时的速度静脉输注大肠杆菌内毒素（LPS），持续6小时。在LPS输注1小时后，以初量（30毫克/千克） - 持续（30毫克/千克/小时）静脉输注DCA，持续5小时。将这些接受DCA治疗的内毒素血症小型猪（DE组）与仅给予内毒素的一组小型猪（n = 8，E组）进行统计学比较。在DCA输注的最后一小时，DE组动脉血乳酸浓度最终显著降低（19.2±1.0毫克/分升）（P≤0.05），低于E组（39.3±7.7毫克/分升）。DE组逐渐出现的低血糖低于E组，并且在实验的最后一小时显著降低（P≤0.05）（分别为33.6±11.5与50.6±10.0毫克/分升），这是由于肝糖异生减少所致，表现为葡萄糖相对出现率（%Ra）降低、肝葡萄糖输出和乳酸摄取减少。在整个治疗期间，DE组胰腺胰岛素分泌的大幅相对减少导致其血清胰岛素水平低于E组。DE组的致死率（60%）与E组（67%）相比没有变化。尽管DCA能够降低动脉血乳酸浓度，但单独使用DCA似乎并不是内毒素血症的有效治疗方法。
