Ethyl pyruvate improves systemic and hepatosplanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia.
OBJECTIVE
To investigate the systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of delayed treatment with ethyl pyruvate in a long-term porcine model of hyperdynamic endotoxemia.


METHODS
Prospective, randomized, controlled experimental study with repeated measures.


METHODS
Investigational animal laboratory.


METHODS
Anesthetized, mechanically ventilated, and instrumented pigs.


METHODS
After 12 hrs of continuous infusion of lipopolysaccharide and hydroxyethyl starch to keep mean arterial pressure >60 mm Hg, swine randomly received placebo (Ringer's solution; control group, n = 11) or ethyl pyruvate in lactated Ringer's solution (n = 8; 0.03 g.kg(-1) loading dose over 10 mins, thereafter 0.03 g.kg(-1)hr(-1) for 12 hrs).


RESULTS
Whereas mean arterial pressure significantly decreased in control animals, mean arterial pressure was maintained at the baseline level in pigs treated with ethyl pyruvate. Global oxygen uptake was comparable, so that the trend toward a higher oxygen transport and the significantly higher mixed venous hemoglobin oxygen saturation resulted in a significantly lower oxygen extraction in the ethyl pyruvate group. Ethyl pyruvate reduced intrapulmonary venous admixture and resulted in significantly greater Pa(O2)/F(IO2) ratios. Despite comparable urine production in the two groups during the first 18 hrs of endotoxemia, ethyl pyruvate significantly increased diuresis during the last 6 hrs of the study. Lipopolysaccharide-induced systemic and regional venous metabolic acidosis was significantly ameliorated by ethyl pyruvate. Endotoxemia increased both blood nitrate + nitrite and isoprostane concentrations, and ethyl pyruvate attenuated the response of these markers of nitric oxide production and lipid peroxidation.


CONCLUSIONS
Ethyl pyruvate infusion resulted in improved hemodynamic stability and ameliorated acid-base derangements induced by chronic endotoxemia in pigs. Reduced oxidative stress and an decreased nitric oxide release probably contributed to these effects.
Hauser
Balázs
B
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
Kick
Jochen
J
Asfar
Pierre
P
Ehrmann
Ulrich
U
Albicini
Maura
M
Vogt
Josef
J
Wachter
Ulrich
U
Brückner
Uwe Bernd
UB
Fink
Mitchell P
MP
Radermacher
Peter
P
Bracht
Hendrik
H
D000138:Acidosis / Q000188:drug therapy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008102:Liver Circulation / Q000187:drug effects*; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects; D011773:Pyruvates / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D012121:Respiration, Artificial; D012151:Resuscitation; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine
D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D011773:Pyruvates; C046522:ethyl pyruvate; D010100:Oxygen