title: Lethality of standard total parenteral nutrition following major liver resection in rats is prevented by high arginine and high branched chain amino acids but not by glutamine.
abstract: Standard total parenteral nutrition (TPN), with or without fat, in amounts approximating the ad libitum intake of normal rats is highly lethal for rats following 70% hepatectomy. Because of significant metabolic changes including alterations of branched chain amino acids (BCAA), arginine (ARG), and glutamine (GLN) associated with serious injury, sepsis, and liver dysfunction, we hypothesized that (1) increasing concentrations of BCAA and ARG in TPN and (2) including glutamine in the TPN may diminish the lethality. Male Sprague-Dawley rats with 70% hepatectomy and jugular vein catheterization were divided into groups. Two sets of experiments were conducted. In Experiment 1, the effects of varying concentrations of BCAA and ARG in the TPN infusate, singly and together, were assessed: Group 1, Standard TPN (19% BCAA, 4.8 g ARG/L); Group II, High BCAA TPN (35% BCAA, 4.8 g ARG/L); Group III, High ARG TPN (19% BCAA, 9.6 g ARG/L); Group IV, High ARG, High BCAA TPN (35% BCAA, 9.6 g ARG/L; Group V, chow and tap water ad libitum. In experiment 2, the effect of 2% GLN in TPN was evaluated: Group A, Standard TPN and Group B, 2% GLN TPN. All infusates were isocaloric (216 Kcal/Kg/d) and isonitrogenous (1.94 g N/Kg/d) delivered at half concentration on postoperative day 1, 3/4 concentration on postoperative day 2, and at full concentration thereafter. Experiment 1: Thirty-three to 36% of rats in Groups I (Standard TPN) (4/11), II (High BCAA TPN) (4/11) and III (High ARG TPN) (4/12) died within 6 days. In sharp contrast, none died in Groups IV (High BCAA, High ARG TPN) and V (rat chow and tap water) (P < 0.05 in each comparison). Among rats in the 4 TPN groups surviving 7 days, there were no significant differences in body weight change (minus 3-4%), spleen or lung weight, extent of liver regeneration (61-66%). Serum total protein and albumin were significantly higher in Group V (chow-fed) (similar to values in normal rats) than in Groups I-IV, P < 0.05 in each case. Serum total bilirubin was significantly higher in Group I than in normals and in Groups II, III, and V. Serum lactate dehydrogenase levels were similar in normals and all 5 groups. Serum aspartate amino transferase level was higher in Group I than in normals but not significantly different from those groups II-V; the latter were similar to normals. Experiment 2: Thirty percent of rats in Groups A (Standard TPN) (3/10) and B (GLN TPN) (3/10) died within 6 days. Among rats surviving for 7 days, body weight change (minus 3-5%), liver regeneration (67-70%), and liver tests were similar in both groups. TPN modified to contain high concentrations of both BCAA and ARG (but not of either alone) prevented the high frequency of lethality induced by standard TPN in rats with 70% hepatectomy. No such salutary effect was shown by modifying the TPN to contain 2% GLN. The striking benefit observed when TPN containing high BCAA and high ARG was infused may be due to the high BCAA leading toward normalization of serum amino acid levels, reducing proteolysis, increasing protein synthesis, and accelerating early liver regeneration, combined with the high ARG likely reducing serum ammonia and leading to increased host defense, and perhaps, thereby, preventing bacterial translocation and bacteremia.
authors.affiliation: Department of Surgery, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Qiu
authors.forename: H M
authors.initials: HM
authors.lastname: Delany
authors.forename: E L
authors.initials: EL
authors.lastname: Teh
authors.forename: M L
authors.initials: ML
authors.lastname: Gliedman
authors.forename: C J
authors.initials: CJ
authors.lastname: Chang
authors.forename: S M
authors.initials: SM
authors.lastname: Levenson
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D005973:Glutamine / Q000008:administration & dosage* / Q000494:pharmacology; D006498:Hepatectomy / Q000401:mortality; D008099:Liver / Q000187:drug effects; D008111:Liver Function Tests; D008115:Liver Regeneration; D008297:Male; D010289:Parenteral Nutrition, Total; D051381:Rats; D012984:Software; D013997:Time Factors
chemical_list: D000597:Amino Acids, Branched-Chain; D005973:Glutamine; D001120:Arginine