Holloway P A, Knox K, Bajaj N, Chapman D, White N J, O'Brien R, Stacpoole P W, Krishna S
Nuffield Departments of Clinical Biochemistry, John Radcliffe Hospital, Oxford, United Kingdom.
Exp Parasitol. 1995 Jun;80(4):624-32. doi: 10.1006/expr.1995.1078.
The kinetics of Plasmodium berghei infection and the development of lactic acidosis, hypoglycemia, and anemia were defined in young Wistar rats. This model of metabolic dysfunction, which is similar to that of severe human malaria, was used to test the hypothesis that dichloroacetate, a treatment for lactic acidosis, prolonged survival in rats receiving a single antimalarial dose of quinine (20 mg/kg). Rats with hyperlactatemia (lactate > 5 mmol/liter, N = 183) were randomized to receive either dichloroacetate (100 mg/kg, N = 99) or saline (N = 84) and were monitored for outcome (survival or death) for 50 hr. Logistic regression modeling adjusting for baseline venous lactate concentration demonstrated that dichloroacetate increases survival rates in rats with venous lactate concentrations between 5 and 8.9 mmol/liter (odds ratio > 2.2, P < 0.021). This is the first demonstration that specific intervention to treat lactic acidosis can prolong survival and suggests that dichloroacetate may be useful as adjunctive therapy in the management of lactic acidosis complicating severe falciparum malaria.
在幼年Wistar大鼠中确定了伯氏疟原虫感染的动力学以及乳酸酸中毒、低血糖和贫血的发展情况。这种代谢功能障碍模型与严重人类疟疾的模型相似，被用于检验以下假设：乳酸酸中毒的治疗药物二氯乙酸可延长接受单剂量抗疟药奎宁（20 mg/kg）的大鼠的存活时间。将高乳酸血症大鼠（乳酸>5 mmol/升，N = 183）随机分为两组，分别接受二氯乙酸（100 mg/kg，N = 99）或生理盐水（N = 84）治疗，并监测50小时的结果（存活或死亡）。对基线静脉乳酸浓度进行校正的逻辑回归模型表明，二氯乙酸可提高静脉乳酸浓度在5至8.9 mmol/升之间的大鼠的存活率（优势比>2.2，P<0.021）。这是首次证明治疗乳酸酸中毒的特异性干预措施可延长存活时间，并表明二氯乙酸可能作为辅助治疗用于伴有严重恶性疟乳酸酸中毒的管理。
