From the Department of Biochemistry and Molecular Genetics (J.A.R., M.J.W., K.C.H., A.D.), University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado; Denver Health Hospital - (E.E.M., A.G., J.C.), Denver, Colorado; Department of Surgery (A.L.S., H.B.M., M.F., G.N., A.B.), University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado; Naval Medical Research Unit San Antonio (L.J.S., F.R.S.), JBSA-Ft. Sam Houston, Texas; Department of Paediatrics (C.C.S.), University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado; and Bonfils Blood Center (C.C.S.), Denver, Colorado.
J Trauma Acute Care Surg. 2018 Mar;84(3):537-541. doi: 10.1097/TA.0000000000001721.
Plasma levels of lactate and succinate are predictors of mortality in critically injured patients in military and civilian settings. In relative terms, these metabolic derangements have been recapitulated in rodent, swine, and nonhuman primate models of severe hemorrhage. However, no direct absolute quantitative comparison has been evaluated across these species.
Ultra-high pressure liquid chromatography-mass spectrometry with stable isotope standards was used to determine absolute concentrations of baseline and postshock levels of lactate and succinate in rats, pigs, macaques, and injured patients.
Baseline levels of lactate and succinate were most comparable to humans in macaques, followed by pigs and rats. Baseline levels of lactate in pigs and baseline and postshock levels of lactate and succinate in rats were significantly higher than those measured in macaques and humans. Postshock levels of lactate and succinate in pigs and macaques, respectively, were directly comparable to measurements in critically injured patients.
Acknowledging the caveats associated with the variable degrees of shock in the clinical cohort, our data indicate that larger mammals represent a better model than rodents when investigating metabolic derangements secondary to severe hemorrhage.
在军事和民用环境中,创伤患者的血浆乳酸和琥珀酸水平是预测死亡率的指标。在相对意义上,这些代谢紊乱在严重出血的啮齿动物、猪和非人灵长类动物模型中得到了重现。然而,这些物种之间并没有进行直接的绝对定量比较。
采用超高压液相色谱-质谱联用技术和稳定同位素标准,测定大鼠、猪、猕猴和创伤患者的基础和休克后乳酸和琥珀酸的绝对浓度。
在猕猴中,乳酸和琥珀酸的基础水平与人类最为相似,其次是猪和大鼠。猪的乳酸基础水平和大鼠的乳酸基础和休克后水平均明显高于猕猴和人类。猪和猕猴的休克后乳酸和琥珀酸水平分别与重症创伤患者的测量值直接可比。
考虑到临床队列中休克程度的差异,我们的数据表明,在研究严重出血引起的代谢紊乱时,较大的哺乳动物比啮齿动物更能代表一种更好的模型。