Adenosine triphosphate-magnesium dichloride during hyperdynamic porcine endotoxemia: effects on hepatosplanchnic oxygen exchange and metabolism.
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.
Asfar
Pierre
P
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
Nalos
Marek
M
Pittner
Antje
A
Theisen
Marc
M
Ichai
Carole
C
Ploner
Franz
F
Georgieff
Michael
M
Ince
Can
C
Brückner
Uwe Bernd
UB
Leverve
Xavier Maurice
XM
Radermacher
Peter
P
Froeba
Gebhard
G
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
D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000255:Adenosine Triphosphate; D010100:Oxygen