Isoflurane pretreatment lowers portal venous resistance by increasing hepatic heme oxygenase activity in the rat liver in vivo.
OBJECTIVE
The heme oxygenase (HO) system contributes to the maintenance of hepatic perfusion and integrity. It was the objective of this study to determine the influence of isoflurane (ISO) on hepatic HO-1 induction and its impact on hepatic hemodynamics.


METHODS
Rats were pretreated with or without ISO for 5h. After hemodynamic measurements by pressure-, laser doppler-, and ultrasound based techniques, the liver was harvested. HO-1 was analyzed by an HO activity assay, Northern- and Western blotting.


RESULTS
ISO pretreatment induced hepatic HO-1 mRNA and protein resulting in an increase of HO activity. No effect on hsp-27, hsp-70 and hsp-90 mRNA could be observed. ISO lowered portal resistance. HO inhibition by tin protoporphyrine IX increased portal resistance in ISO pretreated animals up to control levels. This was associated with an increase in portal pressure and a reduction of portal flow. Microvascular flux was also impaired after HO blockade and ISO. However, hepatic arterial and systemic hemodynamics remained unchanged, indicating a specific effect within the portal vascular bed.


CONCLUSIONS
ISO pretreatment induces hepatic HO-1 mRNA and protein followed by an increase in HO activity, thereby reducing portal resistance. These findings indicate a beneficial effect of ISO on hepatic hemodynamics in vivo.
Schmidt
Rene
R
Department of Anesthesiology and Critical Care Medicine, University Hospital Freiburg, Hugstetterstrasse 55, D-79106 Freiburg, Germany.
Hoetzel
Alexander
A
Baechle
Tilo
T
Loop
Torsten
T
Humar
Matjaz
M
Bauer
Michael
M
Pahl
Heike L
HL
Geiger
Klaus K
KK
Pannen
Benedikt H J
BH
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing); D007530:Isoflurane / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply / Q000201:enzymology; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009363:Neoplasm Proteins / Q000235:genetics; D010105:Oxygenases / Q000235:genetics* / Q000378:metabolism; D011169:Portal Vein / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D007530:Isoflurane; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat