title: A comparison of hepatic ischemia/hypoxia-reperfusion injury models.
abstract: BACKGROUND
  A number of hepatic ischemia/hypoxia-reperfusion models have been described. This study characterised the functional and structural changes induced by the most commonly used in vivo and in situ models for hypoxia/ischemia-reperfusion in the rat liver.
  
  
  METHODS
  A range of no-flow, slow-flow and lobar ischemia and reperfusion models were established in the rat liver. Changes following reperfusion were monitored using physiological, biochemical, histological and pharmacological assessments, including bile production, oxygen consumption, lignocaine extraction, enzyme release, and disposition of exogenous markers.
  
  
  RESULTS
  Short periods of hepatic ischemia/hypoxia-reperfusion led to minimal changes in liver function whereas long periods of ischemia-reperfusion led to substantial liver injury. The most severe injury was found with the slow flow, reflow model. The formation of cell vacuoles, blebs and focal hepatitis were the most important liver morphological changes observed as a consequence of ischemia/hypoxia. The major liver histological findings after reperfusion were dispersed apoptosis and local necrosis. Hepatic ischemia/hypoxia-reperfusion was also associated with significant changes in the hepatic extracellular and intracellular spaces.
  
  
  CONCLUSIONS
  The morphology and function of the liver associated with a range of hepatic ischemia/hypoxia-reperfusion models varies with the duration of the insult and between models. The choice of model is therefore an important consideration in seeking to resolve any particular hypothesis associated with hepatic ischemia/hypoxia-reperfusion.
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Iran. Electronic address: harab@ut.ac.ir.
authors.forename: Hossein-Ali
authors.initials: HA
authors.lastname: Arab
authors.forename: Kee
authors.initials: K
authors.lastname: Cheung
authors.forename: Peter E
authors.initials: PE
authors.lastname: Hickman
authors.forename: Julia M
authors.initials: JM
authors.lastname: Potter
authors.forename: Neal I
authors.initials: NI
authors.lastname: Walker
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D000818:Animals; D017209:Apoptosis; D001646:Bile / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008107:Liver Diseases / Q000503:physiopathology*; D008111:Liver Function Tests; D009336:Necrosis; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D012720:Severity of Illness Index; D013997:Time Factors
keywords: Apoptosis; Liver function; Liver ischemia; Reperfusion injury; Slow flow; Solute disposition