"Immunonutrition" Has Failed To Improve Peritonitis-Induced Septic Shock In Rodents

BackgroundImmunonutrition 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.DesignRats were fed with enteral Peptamen (R) HN (HN group), Peptamen (R) AF containing n-3 PUFAs (AF group) or Peptamen (R) 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.ResultsCompared 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-kappa B (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, beta-actin ratio, p<0.05) and pI kappa B 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, beta-actin ratio, p<0.05), nitric oxide and prostacyclin production in septic rats.ConclusionsAlthough 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.