"Immunonutrition" Has Failed to Improve Peritonitis-Induced Septic Shock in Rodents

PLoS One. 2016 Jan 25;11(1):e0147644. doi: 10.1371/journal.pone.0147644. eCollection 2016.

Abstract

Background: Immunonutrition in sepsis, including n-3 poly-unsaturated fatty acids (PUFAs) or L-arginine supplementation, is a controversial issue that has yielded a great number of studies for the last thirty-five years, and the conclusions regarding the quantity and quality of this support in patients are deceiving. The aim of the present experimental study is to investigate the effects of a pretreatment with enteral nutrition enriched with n-3 PUFAs or L-arginine on vascular dysfunctions, inflammation and oxidative stress during septic shock in rats.

Design: Rats were fed with enteral Peptamen® HN (HN group), Peptamen® AF containing n-3 PUFAs (AF group) or Peptamen® AF enriched with L-arginine (AFA group). On day 4, peritonitis by cecal ligation and puncture (CLP) was performed. Rats were resuscitated (H18) once septic shock was established. After a 4-hour resuscitation, vessels and organs were harvested to assess inflammation, superoxide anion, nitric oxide and prostacyclin levels. Ex-vivo vascular reactivity was also performed.

Results: Compared to CLP-AF or CLP-HN groups, 47.6% of CLP-AFA rats died before the beginning of hemodynamic measurements (vs. 8.0% and 20.0% respectively, p<0.05). AF and AFA rats required significantly increased norepinephrine infusion rates to reach the mean arterial pressure objective, compared to CLP-HN rats. Both CLP-AF and CLP-AFA reduced mesenteric resistance arterial contractility, decreased vascular oxidative stress, but increased NF-κB (0.40±0.15 in CLP-AF and 0.69±0.06 in CLP-AFA vs. 0.09±0.03 in SHAM rats and 0.30±0.06 in CLP-HN, ß-actin ratio, p<0.05) and pIκB expression (0.60±0.03 in CLP-AF and 0.94±0.15 in CLP-AFA vs. 0.04±0.01 in SHAM rats and 0.56±0.07 in CLP-HN, ß-actin ratio, p<0.05), nitric oxide and prostacyclin production in septic rats.

Conclusions: Although n-3 PUFAs or L-arginine supplementation exhibited an antioxidant effect, it worsened the septic shock-induced vascular dysfunction. Furthermore, mortality was higher after L-arginine supplementation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / therapeutic use
  • Fatty Acids, Omega-3 / therapeutic use
  • Male
  • Peritonitis / drug therapy*
  • Peritonitis / mortality
  • Rats
  • Rats, Wistar
  • Sepsis / drug therapy
  • Sepsis / mortality
  • Shock, Septic / drug therapy*
  • Shock, Septic / mortality

Substances

  • Fatty Acids, Omega-3
  • Arginine

Grants and funding

Funding source: this work has been in part supported by the Association for Research Development in Intensive Care (Association pour le Développement de la Recherche En Réanimation, ADRER) and grant from Nestlé. The authors also thank the Alsacian Association for Respiratory Failure Help at Home (Association Des Insuffisants Respiratoires Alsace Lorraine, ADIRAL) for its financial and material support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.