title: Modulation of systemic hemodynamics by exogenous L-arginine in normal and bacteremic sheep.
abstract: OBJECTIVE
  To investigate whether exogenous L-arginine, the substrate for nitric oxide synthase, modulates systemic hemodynamics in sepsis.
  
  
  METHODS
  Prospective, controlled study in a sheep model of sepsis.
  
  
  METHODS
  Animal research facility in a university hospital.
  
  
  METHODS
  Adult sheep weighing between 35 and 55 kg.
  
  
  METHODS
  Adult sheep sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with L-arginine, and septic treated with L-arginine. Sepsis was induced by the intravenous administration of Escherichia coli (1.5x10(8) colony-forming units/kg for 30 mins). L-arginine was administered as an intravenous bolus (200 mg/kg for 10 mins) before the septic challenge followed by 200 mg/kg/hr for 300 mins.
  
  
  RESULTS
  Sepsis induced a state of acidosis, hyperlactatemia, hypoxemia, and gastric intramucosal acidosis. During the first 30 mins after the septic challenge, there was a decrease in cardiac index and blood pressure, and an increase in systemic vascular resistance. Thereafter, blood pressure returned to baseline values, and systemic vascular resistance fell. Treatment with L-arginine in nonseptic sheep did not induce any biochemical or hemodynamic effect. In septic sheep, treatment with L-arginine was associated with a greater increase in systemic vascular resistance during the first 30 mins, and a more marked decrease in blood pressure and systemic vascular resistance after 180 mins.
  
  
  CONCLUSIONS
  Exogenous administration of L-arginine does not induce hemodynamic effects in normal animals, exacerbates the acute vasoconstriction associated with the intravenous infusion of E. coli and potentiates the sepsis-induced vasodilation. Our results suggest that a) nitric oxide production is not constitutively modulated by exogenous L-arginine, b) L-arginine probably enhances the sepsis-induced sympathetic discharge, and c) L-arginine becomes rate-limiting for the formation of nitric oxide at approximately 3 hrs after the initiation of the septic challenge.
authors.affiliation: Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Lorente
authors.forename: M A
authors.initials: MA
authors.lastname: Delgado
authors.forename: C
authors.initials: C
authors.lastname: Tejedor
authors.forename: E
authors.initials: E
authors.lastname: Mon
authors.forename: M
authors.initials: M
authors.lastname: Hervás
authors.forename: T
authors.initials: T
authors.lastname: Pascual
authors.forename: P
authors.initials: P
authors.lastname: Fernández-Segoviano
authors.forename: G
authors.initials: G
authors.lastname: Rieppi
authors.forename: A
authors.initials: A
authors.lastname: Soler
authors.forename: D
authors.initials: D
authors.lastname: Ayuso
authors.forename: A
authors.initials: A
authors.lastname: Esteban
mesh_terms: D000138:Acidosis / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D016470:Bacteremia / Q000097:blood / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D006863:Hydrogen-Ion Concentration; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000097:blood; D007970:Leukopenia / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012121:Respiration, Artificial; D012756:Sheep; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D019344:Lactic Acid; D001120:Arginine