Ten Have Gabriella A M, Engelen Mariëlle P K J, Wolfe Robert R, Deutz Nicolaas E P
Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, Texas; and.
Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Am J Physiol Endocrinol Metab. 2017 Jun 1;312(6):E519-E529. doi: 10.1152/ajpendo.00351.2016. Epub 2017 Mar 14.
The primed-continuous (PC) phenylalanine (Phe) stable isotope infusion methodology is often used as a proxy for measuring whole body protein breakdown (WbPB) in sepsis. It is unclear if WbPB data obtained by an easy-to-use single IV Phe isotope pulse administration (PULSE) are comparable to those by PC. Compartmental modeling with PULSE could provide us more insight in WbPB in sepsis. Therefore, in the present study, we compared PULSE with PC as proxy for WbPB in an instrumented pig model with induced severe sepsis (Healthy: = 9; Sepsis: = 13). Seventeen hours after sepsis induction, we compared the Wb rate of appearance (WbR) of Phe obtained by PC (L-[-C]Phe) and PULSE (L-[N]Phe) in arterial plasma using LC-MS/MS and (non)compartmntal modeling. PULSE-WbR was highly correlated with PC-WbR ( = 0.732, < 0.0001) and WbPB ( = 0.897, < 0.0001) independent of the septic state. PULSE-WbR was 1.6 times higher than PC-WbR ( < 0.001). Compartmental and noncompartmental PULSE modeling provide comparable WbR values, although compartmental modeling was more sensitive. WbPB was elevated in sepsis (Healthy: 3,378 ± 103; Sepsis: 4,333 ± 160 nmol·kg BW·min, = 0.0002). With PULSE, sepsis was characterized by an increase of the metabolic shunting (Healthy: 3,021 ± 347; Sepsis: 4,233 ± 344 nmol·kg BW·min, = 0.026). Membrane transport capacity was the same. Both PC and PULSE methods are able to assess changes in WbR of plasma Phe reflecting WbPB changes with high sensitivity, independent of the (patho)physiological state. The easy-to-use (non)compartmental PULSE reflects better the real WbPB than PC. With PULSE compartmental analysis, we conclude that the membrane transport capacity for amino acids is not compromised in severe sepsis.
预充连续（PC）苯丙氨酸（Phe）稳定同位素输注方法常用于替代测量脓毒症患者的全身蛋白质分解代谢（WbPB）。目前尚不清楚通过易于使用的单次静脉注射Phe同位素脉冲给药（PULSE）获得的WbPB数据是否与PC方法获得的数据具有可比性。使用PULSE进行房室模型分析可以让我们更深入地了解脓毒症患者的WbPB情况。因此，在本研究中，我们在诱导严重脓毒症的仪器化猪模型中（健康组：n = 9；脓毒症组：n = 13），比较了PULSE和PC作为WbPB替代指标的差异。在诱导脓毒症17小时后，我们使用液相色谱 - 串联质谱法（LC-MS/MS）和（非）房室模型分析，比较了通过PC（L-[-C]Phe）和PULSE（L-[N]Phe）在动脉血浆中获得的Phe的Wb出现率（WbR）。PULSE-WbR与PC-WbR高度相关（r = 0.732，P < 0.0001），与WbPB也高度相关（r = 0.897，P < 0.0001），且与脓毒症状态无关。PULSE-WbR比PC-WbR高1.6倍（P < 0.001）。房室模型和非房室模型的PULSE分析提供了可比的WbR值，尽管房室模型更敏感。脓毒症患者的WbPB升高（健康组：3,378 ± 103；脓毒症组：4,333 ± 160 nmol·kg BW·min，P = 0.0002）。使用PULSE方法时，脓毒症的特征是代谢分流增加（健康组：3,021 ± 347；脓毒症组：4,233 ± 344 nmol·kg BW·min，P = 0.026）。膜转运能力相同。PC和PULSE方法都能够高度敏感地评估血浆Phe的WbR变化，反映WbPB的变化，且与（病理）生理状态无关。易于使用的（非）房室PULSE比PC能更好地反映真实的WbPB。通过PULSE房室分析，我们得出结论，严重脓毒症患者氨基酸的膜转运能力未受损。
