Arginine deficiency in sepsis may impair nitric oxide (NO) production for local perfusion and add to the catabolic state. In contrast, excessive NO production has been related to global haemodynamic instability. Therefore, the aim of the present study was to investigate the dose–response effect of intravenous arginine supplementation in post-absorptive patients with septic shock on arginine-NO and protein metabolism and on global and regional haemodynamics. Eight critically ill patients with a diagnosis of septic shock participated in this short-term (8 h) dose–response study. L-Arginine-HCl was continuously infused [intravenously (IV)] in three stepwise-increasing doses (33, 66 and 99 μmol·kg−1·h−1). Whole-body arginine-NO and protein metabolism were measured using stable isotope techniques, and baseline values were compared with healthy controls. Global and regional haemodynamic parameters were continuously recorded during the study. Upon infusion, plasma arginine increased from 48±7 to 189±23 μmol·l−1 (means±S.D.; P<0.0001). This coincided with increased de novo arginine (P<0.0001) and increased NO production (P<0.05). Sepsis patients demonstrated elevated protein breakdown at baseline (P<0.001 compared with healthy controls), whereas protein breakdown and synthesis both decreased during arginine infusion (P<0.0001). Mean arterial and pulmonary pressure and gastric mucosal-arterial partial pressure of carbon dioxide difference (Pr-aCO2) gap did not alter during arginine infusion (P>0.05), whereas stroke volume (SV) increased (P<0.05) and arterial lactate decreased (P<0.05). In conclusion, a 4-fold increase in plasma arginine with intravenous arginine infusion in sepsis stimulates de novo arginine and NO production and reduces whole-body protein breakdown. These potential beneficial metabolic effects occurred without negative alterations in haemodynamic parameters, although improvement in regional perfusion could not be demonstrated in the eight patients with septic shock who were studied.
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January 2015
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Research Article|
August 29 2014
Arginine infusion in patients with septic shock increases nitric oxide production without haemodynamic instability
Yvette C. Luiking;
*Center for Translational Research in Aging & Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, TX, U.S.A.
Correspondence: Dr Yvette C. Luiking (email [email protected]).
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Martijn Poeze;
Martijn Poeze
†Maastricht University Medical Center+, Department of Surgery and Intensive Care Medicine, Maastricht, The Netherlands
‡NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht, The Netherlands
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Nicolaas E. Deutz
Nicolaas E. Deutz
*Center for Translational Research in Aging & Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, TX, U.S.A.
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Publisher: Portland Press Ltd
Received:
June 02 2014
Revision Received:
July 14 2014
Accepted:
July 18 2014
Accepted Manuscript online:
July 18 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 128 (1): 57–67.
Article history
Received:
June 02 2014
Revision Received:
July 14 2014
Accepted:
July 18 2014
Accepted Manuscript online:
July 18 2014
Citation
Yvette C. Luiking, Martijn Poeze, Nicolaas E. Deutz; Arginine infusion in patients with septic shock increases nitric oxide production without haemodynamic instability. Clin Sci (Lond) 1 January 2015; 128 (1): 57–67. doi: https://doi.org/10.1042/CS20140343
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