Effects of endotoxin on lactate metabolism in humans.

Effects of endotoxin on lactate metabolism in humans.
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DOI:
10.1186/cc11444
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发表时间:
2012-07-27
期刊:
Critical care (London, England)
影响因子:
--
通讯作者:
Berger MM
Berger MM
中科院分区:
其他
文献类型:
--
作者:
Michaeli B;Martinez A;Revelly JP;Cayeux MC;Chioléro RL;Tappy L;Berger MM

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高乳酸血症是脓毒症代谢反应的一个重要组成部分。在重症患者中,高乳酸血症与基础疾病的严重程度有关。在这一过程中,可能既涉及到产量的增加,也涉及到利用和清除量的减少,但它们的相对作用仍不得而知。本研究的目的是评估全身和肌肉乳酸生产和全身乳酸清除健康志愿者,使用静脉内毒素(LPS)的挑战。14名健康男性志愿者入组2项连续研究(试验1中n = 6,试验2中n = 8)。每例受试者以随机顺序参加两个研究日之一(内毒素注射LPS日和生理盐水注射安慰剂日),间隔至少一周。在试验1中,使用微透析监测他们的肌肉乳酸代谢。在试验2中,通过持续输注外源性乳酸盐监测其全身乳酸盐代谢。通过间接量热法监测能量代谢,并用6,6-H2葡萄糖测量葡萄糖动力学。在两项试验中,LPS增加能量消耗(p = 0.011)、脂质氧化(p<0.0001)和血浆乳酸浓度(p = 0.016)。在试验1中,肌肉微透析液中的乳酸盐浓度高于血液中的乳酸盐浓度,表明肌肉产生乳酸盐。然而,这与有和没有LPS相似。在试验2中,LPS后计算的全身乳酸产生增加(p = 0.031),而乳酸清除率保持不变。LPS给药通过增加乳酸产生而不是通过降低乳酸清除来增加乳酸血症。然而,肌肉不太可能是乳酸产生增加的主要原因。ClinicalTrials.gov www.example.com
Hyperlactatemia represents one prominent component of the metabolic response to sepsis. In critically ill patients, hyperlactatemia is related to the severity of the underlying condition. Both an increased production and a decreased utilization and clearance might be involved in this process, but their relative contribution remains unknown. The present study aimed at assessing systemic and muscle lactate production and systemic lactate clearance in healthy human volunteers, using intravenous endotoxin (LPS) challenge. Fourteen healthy male volunteers were enrolled in 2 consecutive studies (n = 6 in trial 1 and n = 8 in trial 2). Each subject took part in one of two investigation days (LPS-day with endotoxin injection and placebo-day with saline injection) separated by one week at least and in a random order. In trial 1, their muscle lactate metabolism was monitored using microdialysis. In trial 2, their systemic lactate metabolism was monitored by means of a constant infusion of exogenous lactate. Energy metabolism was monitored by indirect calorimetry and glucose kinetics was measured with 6,6-H2 glucose. In both trials, LPS increased energy expenditure (p = 0.011), lipid oxidation (p<0.0001), and plasma lactate concentration (p = 0.016). In trial 1, lactate concentration in the muscle microdialysate was higher than in blood, indicating lactate production by muscles. This was, however, similar with and without LPS. In trial 2, calculated systemic lactate production increased after LPS (p = 0.031), while lactate clearance remained unchanged. LPS administration increases lactatemia by increasing lactate production rather than by decreasing lactate clearance. Muscle is, however, unlikely to be a major contributor to this increase in lactate production. ClinicalTrials.gov NCT01647997
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