title: Hemoglobin-glutamer 200 reduces reperfusion injury of the cold preserved rat liver by induction of heme oxygenase-1.
abstract: Microcirculatory failure after cold liver preservation and reperfusion impairs tissue oxygenation and causes additional organ damage. Hemoglobin-glutamer (HbG) 200 is a hemoglobin-based oxygen carrying solution capable to improve organ oxygenation. The aim of this study was to evaluate its potential to decrease reperfusion injury after cold liver preservation. Therefore, Wistar rat livers were stored at 4 degrees C for 24 h and reperfused in the isolated perfused rat liver model with a sanguineous perfusate for 180 min. The perfusate consisted of rat blood and Krebs-Henseleit solution (Group A), supplemented by either HES 6% (Group B), or HbG (Groups C and D). In Group D heme oxygenase (HO) activity was blocked by intraperitoneal tin protoporphyrin-IX application before organ harvest. HbG supplementation increased the perfusate hemoglobin by 3,3 g/dL. After 180 min reperfusion perfusate alanine aminotransferase levels (72 +/- 27 micro/L) were significantly reduced in Group C, compared with Groups A and B (140 +/- 28 micro/L and 203 +/- 62 micro/L, respectively). These results correlated with a significant increase of HO-1 expression and activity during reperfusion. These effects could be abolished by tin protoporphyrin-IX application. HbG has been proven to be effective to reduce cold liver preservation-reperfusion injury. The positive effect on reperfusion injury depends on the induction of HO-1, which increases the bilirubin production, an important antioxidant acting as intracellular radical scavenger.
authors.affiliation: Department of General, Visceral, and Pediatric Surgery, University Hospital Düsseldorf, Düsseldorf, Germany. stefan.topp@uni-duesseldorf.de
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Topp
authors.forename: Andreas
authors.initials: A
authors.lastname: Krieg
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.forename: Carina M
authors.initials: CM
authors.lastname: Tidden
authors.forename: Uwe
authors.initials: U
authors.lastname: Ramp
authors.forename: Thomas
authors.initials: T
authors.lastname: Hohlfeld
authors.forename: Arne
authors.initials: A
authors.lastname: Macher
authors.forename: Jan
authors.initials: J
authors.lastname: Schulte am Esch
authors.forename: Claus F
authors.initials: CF
authors.lastname: Eisenberger
authors.forename: Nikolas H
authors.initials: NH
authors.lastname: Stoecklein
authors.forename: Wolfram T
authors.initials: WT
authors.lastname: Knoefel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050377:Cold Ischemia; D004790:Enzyme Induction / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006454:Hemoglobins / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008102:Liver Circulation / Q000187:drug effects; D008111:Liver Function Tests; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion / Q000009:adverse effects; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D006454:Hemoglobins; C402601:hemoglobin glutamer-200; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat