Hepatic O2 exchange and liver energy metabolism in hyperdynamic porcine endotoxemia: effects of iloprost.
OBJECTIVE
To compare the effects of a 12 h continuous infusion of iloprost, a stable prostacyclin analogue, on hepatic blood flow (Qliv), O2 exchange, and energy metabolism during a 24 h hyperdynamic, porcine endotoxemia with volume resuscitation alone.


METHODS
Prospective, randomized, experimental study with repeated measures.


METHODS
Investigational animal laboratory.


METHODS
Twenty-eight domestic pigs: 16 animals during endotoxemia with volume resuscitation alone (ETX), 12 with endotoxemia, volume resuscitation, and treatment with iloprost (ILO).


METHODS
Endotoxemia was initiated by continuous infusion of E. coli lipopolysaccharide. Animals were resuscitated with hetastarch, aimed at maintaining a MAP of > 60 mmHg. After 12 h of endotoxemia, iloprost was administered for 12 h in the treatment group, titrated to avoid pharmacologically induced hypotension (MAP < 60 mmHg).


RESULTS
Iloprost significantly increased Qliv, with no effect on hepatic O2 delivery. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface, as well as HbScO2 frequency distributions--a measure of microcirculatory O2 availability--remained unchanged. Treatment with iloprost, however, 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 endogenous glucose production (EGP) rate, iloprost restored EGP to normal at the end of the experiment.


CONCLUSIONS
Thus, in a clinically relevant model of human sepsis, iloprost did not produce potential adverse effects but rather ameliorated hepatic metabolic disturbances and, thereby, hepatic energy balance.
Träger
K
K
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik für Anästhesiologie, Universiät Ulm, Germany. karl.traeger@medizin.uni-ulm.de
Matejovic
M
M
Zülke
C
C
Vlatten
A
A
Vogt
J
J
Wachter
U
U
Altherr
J
J
Brinkmann
A
A
Jauch
K W
KW
Georgieff
M
M
Radermacher
P
P
D000818:Animals; D001784:Blood Gas Analysis; 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*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D016285:Iloprost / Q000494:pharmacology / Q000627:therapeutic use*; D019344:Lactic Acid / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D011446:Prospective Studies; D019289:Pyruvic Acid / Q000378:metabolism; D011897:Random Allocation; D012151:Resuscitation / Q000379:methods; D013552:Swine; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D006454:Hemoglobins; D008070:Lipopolysaccharides; D014665:Vasodilator Agents; D019344:Lactic Acid; D019289:Pyruvic Acid; D016285:Iloprost