Hepatic oxygen exchange and energy metabolism in hyperdynamic porcine endotoxemia: effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX30.
OBJECTIVE
We compared the effects of thromboxane receptor antagonist and synthase inhibitor DTTX30 on systemic and liver blood flow, oxygen (O2) exchange and energy metabolism during 24 h of hyperdynamic endotoxemia with untreated endotoxemia.


METHODS
Prospective, randomized, experimental study with repeated measures.


METHODS
Investigational animal laboratory.


METHODS
Twenty-seven domestic pigs: 16 during endotoxemia with volume resuscitation alone; 11 with endotoxemia, volume resuscitation and treatment with DTTX30.


METHODS
Continuous infusion of Escherichia coli lipopolysaccharide (LPS) for 24 h together with volume resuscitation. After 12 h of endotoxemia, DTTX30 was administered as a bolus of 0.12 mg kg-1 followed by 12 h continuous infusion of 0.29 mg kg-1 per h.


RESULTS
DTTX30 effectively counteracted the endotoxin-associated increase in TXB2 levels and increased 6-keto-PGF1 alpha with a significant shift of the thromboxane/prostacyclin ratio towards predominance of prostacyclin. DTTX30 prevented the significant progressive endotoxin-induced decrease of mean arterial pressure (MAP) below baseline while maintaining cardiac output (CO), and increased the fractional contribution of liver blood flow to CO without an effect on either hepatic O2 delivery or O2 uptake. The mean capillary hemoglobin O2 saturation (HbO2) on the liver surface and HbO2 frequency distributions remained unchanged as well.


CONCLUSIONS
DTTX30 significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased the endogenous glucose production (EGP) rate, EGP returned towards baseline levels in the DTTX30-treated group. Thus, in our model DTTX30 resulted in hemodynamic stabilization concomitant with improved hepatic metabolic performance.
Träger
K
K
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik für Anästhesiologie, Universität Ulm, Parkstrasse 11, 89073 Ulm, Germany. karl.traeger@medizin.uni-ulm.de
Matejovic
M
M
Vogt
J
J
Zülke
C
C
Vlatten
A
A
Wachter
U
U
Altherr
J
J
Brinkmann
A
A
Brückner
U B
UB
Jauch
K W
KW
Georgieff
M
M
Radermacher
P
P
D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000032:analysis; D002722:Chlorobenzenes / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D005440:Fluid Therapy; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D007773:Lactates / Q000097:blood; D008102:Liver Circulation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects*; D011446:Prospective Studies; D011725:Pyridines / Q000494:pharmacology*; D019289:Pyruvic Acid / Q000097:blood; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013552:Swine
D001786:Blood Glucose; D002722:Chlorobenzenes; C107837:DTTX30; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D007773:Lactates; D011725:Pyridines; D019289:Pyruvic Acid