title: Adenosine triphosphate-magnesium dichloride during hyperdynamic porcine endotoxemia: effects on hepatosplanchnic oxygen exchange and metabolism.
abstract: OBJECTIVE
  To assess the effects of adenosine triphosphate-magnesium dichloride (ATP-MgCl2) on systemic and hepatosplanchnic hemodynamics, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic normotensive porcine endotoxemia.
  
  
  METHODS
  Prospective, randomized, controlled experimental study with repeated measures.
  
  
  METHODS
  Investigational animal laboratory.
  
  
  METHODS
  Seventeen pigs were divided into two groups: eight animals receiving endotoxin served as a control group and nine animals received endotoxin (lipopolysaccharide) and ATP-MgCl2.
  
  
  METHODS
  Pigs were anesthetized, mechanically ventilated, and instrumented. Endotoxemia was achieved by continuous intravenous infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch targeted to maintain mean arterial pressure of >75 mm Hg. Twelve hours after the start of the endotoxin infusion, ATP-MgCl2, or its vehicle, were administered for 12 hrs.
  
  
  RESULTS
  Mean arterial pressure was maintained in the control group because of a sustained increase in cardiac output achieved by fluid resuscitation, whereas ATP-MgCl2 significantly decreased mean arterial pressure because of further systemic vasodilatation. ATP-MgCl2 markedly increased portal venous flow. In contrast to the controls, hepatic arterial flow remained unchanged until the end of the experiment, despite the further increase in cardiac output. The ileal mucosal-arterial PCO2 gap (Delta PCO2) progressively increased (p <.05) in control animals, whereas it was restored to prelipopolysaccharide levels during ATP-MgCl2 infusion. Changes in Delta PCO2 correlated with those of portal vein blood flow in these animals (r = -.68, p <.05). Moreover, ATP-MgCl2 blunted the lipopolysaccharide-induced decrease in hepatic lactate balance but did not affect portal venous pH, hepatosplanchnic oxygen exchange, splanchnic lactate/pyruvate ratios, isoprostane, NO2- + NO3-, cytokine concentrations, or tissue nucleotide content.
  
  
  CONCLUSIONS
  During long-term hyperdynamic porcine endotoxemia, ATP-MgCl2 normalized the otherwise progressive rise of the ileal mucosal-arterial Delta PCO2. Furthermore, it allowed blunting of the continuous decrease in hepatic lactate clearance, thus preserving the metabolic coupling between lactate release from the intestine and lactate utilization by the liver.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.forename: Marek
authors.initials: M
authors.lastname: Nalos
authors.forename: Antje
authors.initials: A
authors.lastname: Pittner
authors.forename: Marc
authors.initials: M
authors.lastname: Theisen
authors.forename: Carole
authors.initials: C
authors.lastname: Ichai
authors.forename: Franz
authors.initials: F
authors.lastname: Ploner
authors.forename: Michael
authors.initials: M
authors.lastname: Georgieff
authors.forename: Can
authors.initials: C
authors.lastname: Ince
authors.forename: Uwe Bernd
authors.initials: UB
authors.lastname: Brückner
authors.forename: Xavier Maurice
authors.initials: XM
authors.lastname: Leverve
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Gebhard
authors.initials: G
authors.lastname: Froeba
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology*; D016753:Interleukin-10 / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008102:Liver Circulation / Q000502:physiology*; D023421:Models, Animal; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011446:Prospective Studies; D013152:Splanchnic Circulation / Q000502:physiology*; D013223:Statistics as Topic; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000255:Adenosine Triphosphate; D010100:Oxygen