title: Dihydralazine treatment limits liver injury after hemorrhagic shock in rats.
abstract: OBJECTIVE
  Impaired hepatic perfusion after hemorrhagic shock frequently results in hepatocellular dysfunction associated with increased mortality. This study characterizes the effect of the vasodilators dihydralazine and urapidil on hepatocellular perfusion and integrity after hemorrhagic shock and resuscitation.
  
  
  METHODS
  Prospective, randomized, controlled experimental study.
  
  
  METHODS
  University experimental laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  To register systemic and regional hepatic hemodynamics, rats (n=6 per group) were instrumented and randomly assigned to the following groups: shock+vehicle; shock+dihydralazine (1.5 mg/kg); or shock+urapidil (3 mg/kg). After 1 hr of hemorrhagic shock, animals were resuscitated for 5 hrs and mean arterial pressure was maintained at 70+/-5 mm Hg by administration of dihydralazine or urapidil. To evaluate hepatic heme oxygenase-1 expression and liver injury (determination of levels of alanine and aspartate aminotransferase [ALT, AST] and histology), an additional series of experiments with six animals per group was performed. At the end of each experiment, animals were killed and blood and liver tissue was obtained for subsequent analyses.
  
  
  RESULTS
  Dihydralazine increased cardiac output and portal and hepatic microvascular flow (p<.05) and reduced liver injury after shock (lower ALT and AST levels [p<.05]; improvement of histopathological changes). In contrast, urapidil had no effect on portal flow or liver injury. Hepatic heme oxygenase-1 mRNA expression was upregulated in animals subjected to hemorrhagic shock but did not differ among experimental groups.
  
  
  CONCLUSIONS
  Dihydralazine increases nutritive portal and hepatic microvascular flow and limits liver injury after hemorrhagic shock. This protective effect appears to be the result of increased cardiac output and increased portal flow. These findings may offer a new strategy for hepatic protection after hemorrhagic shock.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Freiburg, Germany.
authors.forename: Rene
authors.initials: R
authors.lastname: Schmidt
authors.forename: Tilo
authors.initials: T
authors.lastname: Baechle
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoetzel
authors.forename: Torsten
authors.initials: T
authors.lastname: Loop
authors.forename: Matjaz
authors.initials: M
authors.lastname: Humar
authors.forename: Martin
authors.initials: M
authors.lastname: Roesslein
authors.forename: Klaus K
authors.initials: KK
authors.lastname: Geiger
authors.forename: Benedikt H J
authors.initials: BH
authors.lastname: Pannen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004078:Dihydralazine / Q000494:pharmacology / Q000627:therapeutic use*; D051547:Heme Oxygenase-1 / Q000187:drug effects* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D008102:Liver Circulation / Q000187:drug effects; D017114:Liver Failure, Acute / Q000517:prevention & control*; D008297:Male; D008833:Microcirculation; D010879:Piperazines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy*
chemical_list: D000959:Antihypertensive Agents; D010879:Piperazines; C015568:urapidil; D051547:Heme Oxygenase-1; D004078:Dihydralazine