title: Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in pigs: effects on intestinal oxygen exchange and energy balance.
abstract: OBJECTIVE
  To compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), on intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock.
  
  
  METHODS
  Prospective, randomized, experimental study with repeated measures.
  
  
  METHODS
  Investigational animal laboratory.
  
  
  METHODS
  Twenty-seven pigs were divided into three groups: seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA.
  
  
  METHODS
  Pigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels.
  
  
  RESULTS
  ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal PCO2 gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response.
  
  
  CONCLUSIONS
  Neither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Vefahrensentwicklung, Universitätsklinik für Anästhesiologie, Universität Ulm, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Träger
authors.forename: P
authors.initials: P
authors.lastname: Radermacher
authors.forename: K M
authors.initials: KM
authors.lastname: Rieger
authors.forename: R
authors.initials: R
authors.lastname: Grover
authors.forename: A
authors.initials: A
authors.lastname: Vlatten
authors.forename: T
authors.initials: T
authors.lastname: Iber
authors.forename: J
authors.initials: J
authors.lastname: Adler
authors.forename: M
authors.initials: M
authors.lastname: Georgieff
authors.forename: B
authors.initials: B
authors.lastname: Santak
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D010100:Oxygen; D009638:Norepinephrine