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肾上腺素影响下健康人体骨骼肌中的乳酸动力学和线粒体呼吸

Lactate kinetics and mitochondrial respiration in skeletal muscle of healthy humans under influence of adrenaline.

作者信息

Grip Jonathan, Jakobsson Towe, Hebert Christina, Klaude Maria, Sandström Gustaf, Wernerman Jan, Rooyackers Olav

机构信息

*Clintec, Department of Anesthesiology and Intensive Care, Karolinska Institutet and Karolinska University Hospital, 141 86 Huddinge, Sweden.

出版信息

Clin Sci (Lond). 2015 Aug;129(4):375-84. doi: 10.1042/CS20140448.

Abstract

Plasma lactate is widely used as a biomarker in critical illness. The aims of the present study were to elucidate the usefulness of a three-compartment model for muscle lactate kinetics in humans and to characterize the response to an exogenous adrenaline challenge. Repeated blood samples from artery and femoral vein together with blood flow measurements and muscle biopsies were obtained from healthy male volunteers (n=8) at baseline and during an adrenaline infusion. Concentrations of lactate and enrichment of [13C]lactate were measured and kinetics calculated. Mitochondrial activity, glycogen concentration, oxygen uptake and CO2 release were assessed. The adrenaline challenge increased plasma lactate 4-fold as a result of a greater increase in the rate of appearance (R(a)) than the increase in the rate of disappearance (R(d)). Leg muscle net release of lactate increased 3.5-fold, whereas intramuscular production had a high variation but did not change. Mitochondrial state 3 respiration increased by 30%. Glycogen concentration, oxygen uptake and CO2 production remained unchanged. In conclusion a three-compartment model gives additional information to the two-compartment model but, due to its larger variation and invasive muscle biopsy, it is less likely to become a regularly used tool in clinical research. Hyperlactataemia in response to adrenergic stimuli was driven by an elevated lactate release from skeletal muscle most probably due to a redirection of a high intramuscular turnover rather than an increased production.

摘要

血浆乳酸在危重病中被广泛用作生物标志物。本研究的目的是阐明三室模型对人体肌肉乳酸动力学的实用性,并描述对外源性肾上腺素刺激的反应特征。在基线期和肾上腺素输注期间,从健康男性志愿者(n = 8)获取动脉和股静脉的重复血样,同时进行血流测量和肌肉活检。测量乳酸浓度和[13C]乳酸的富集情况,并计算动力学。评估线粒体活性、糖原浓度、氧摄取和二氧化碳释放。肾上腺素刺激使血浆乳酸增加了4倍,这是由于乳酸生成速率(R(a))的增加幅度大于消失速率(R(d))的增加幅度。腿部肌肉乳酸净释放增加了3.5倍,而肌肉内生成变化较大但未改变。线粒体状态3呼吸增加了30%。糖原浓度、氧摄取和二氧化碳生成保持不变。总之,三室模型比两室模型能提供更多信息,但由于其变化较大且需要进行侵入性肌肉活检,不太可能成为临床研究中常用的工具。对肾上腺素刺激的高乳酸血症主要是由于骨骼肌乳酸释放增加所致,这很可能是由于肌肉内高周转率的重新定向,而非生成增加。

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