Xu Hongzhi, Watson Davin, Yu Yong-Ming, Traber Daniel L, Fischer Stefani, Nichols Joan, Deyo Donald, Traber Lillian L, Cortiella Joaquin
Shriners Hospital for Children and Massachusetts General Hospital Boston 02114, USA.
Int J Burns Trauma. 2013 Nov 1;3(4):201-8. eCollection 2013.
The objective of the study is to investigate how L-Arginine pulmonary metabolism is altered in response Pseudomonas aeruginosa (P. aeruginosa) induced septic conditions using an ovine model.
Seven female sheep were infused with a primed-constant infusion of L-[(15)N2-guanidino, 5, 5, (2)H2] L-Arginine for 28 hs. After the initial 4 hs of the L-Arginine infusion, a continuous infusion of live Pseudomonas aeruginosa bacteria started for 24 hs. A NO synthase (NOS) inhibitor, N(G)-Methyl-L-arginine (L-NMA), infusion was added during the last 4 hs of the bacterial infusion. Blood samples were taken at specific time points for isotopic enrichment during control, septic and NOS blocking phases of the study.
We observed that the level of total delivery of L-Arginine to the lungs was significantly decreased in septic phase after 24 hours of pseudomonas infusion. In contrast, the fractional uptake and metabolism of L-Arginine by the lungs was doubled during septic phase relative to the control phase (MARG-basal = 100% vs. MARG-septic = 220 ± 56%, P < 0.05). NO production in the lungs was also significantly increased. Infusion of L-NMA markedly blunted this elevated NO production and attenuated the total arginine metabolized in the septic lungs (Mnitrate-septic = 43.6 ± 5.7 vs. Mnitrate-septic + L-NMA = 13.4 ± 5.1 umol/kg/min; p < 0.05). We demonstrated sepsis induced by P. aeruginosa infusion caused an increase in the fractional uptake and metabolic rate of arginine in the lungs. Furthermore, our data suggests that arginine was mainly consumed via arginine - NO pathway, which might be responsible for this enhanced arginine metabolic activity in the septic lungs.
本研究的目的是使用绵羊模型研究铜绿假单胞菌诱导的脓毒症条件下L-精氨酸肺代谢如何改变。
7只雌性绵羊接受L-[(15)N2-胍基，5,5，(2)H2]L-精氨酸的首剂-持续输注28小时。在L-精氨酸输注的最初4小时后，开始持续输注活的铜绿假单胞菌24小时。在细菌输注的最后4小时加入一氧化氮合酶（NOS）抑制剂N(G)-甲基-L-精氨酸（L-NMA）输注。在研究的对照、脓毒症和NOS阻断阶段的特定时间点采集血样进行同位素富集。
我们观察到，在输注铜绿假单胞菌24小时后的脓毒症阶段，肺中L-精氨酸的总输送水平显著降低。相比之下，脓毒症阶段肺对L-精氨酸的摄取分数和代谢相对于对照阶段增加了一倍（基础MARG = 100% vs. 脓毒症MARG = 220 ± 56%，P < 0.05）。肺中一氧化氮的产生也显著增加。输注L-NMA显著减弱了这种升高的一氧化氮产生，并减弱了脓毒症肺中代谢的总精氨酸（脓毒症硝酸盐M = 43.6 ± 5.7 vs. 脓毒症 + L-NMA硝酸盐M = 13.4 ± 5.1 μmol/kg/min；p < 0.05）。我们证明，铜绿假单胞菌输注诱导的脓毒症导致肺中精氨酸的摄取分数和代谢率增加。此外，我们的数据表明，精氨酸主要通过精氨酸-一氧化氮途径消耗，这可能是脓毒症肺中精氨酸代谢活性增强的原因。
