title: The effects of antioxidants on a porcine model of liver hemorrhage.
abstract: The aim of this study is to assess the efficacy of the combination of N-acetylcysteine (NAC) and deferoxamine (DFO) in the resuscitation from hemorrhagic shock in a porcine model of bleeding during hepatectomy.
  
  
  
  Twenty-one pigs were divided randomly to three groups: Sham (S) group, n = 5; fluid (F) resuscitation group, n = 8; and fluid plus NAC plus DFO (NAC&DFO) resuscitation group, n = 8. The animals of groups F and NAC&DFO were subjected to left hepatectomy and controlled hemorrhage from the traumatic liver surface. Shock was established within 10 minutes and maintained for 30 minutes at mean arterial pressure (MAP) of 30 to 40 mm Hg. Resuscitation followed the shock period with crystalloids and colloids. Group NAC&DFO received additionally NAC and DFO in doses of 200 mg/kg and 65 mg/kg, respectively. The total time of the experiment was 6 hours.
  
  
  
  Animal weight, blood loss, excised liver mass, and MAP at the end of the shock period were comparable between experimental groups. Group NAC&DFO received significantly lower volume of both crystalloids and colloids (35% and 42% less, respectively) compared to group F. Hepatocellular proliferation (proliferating cell nuclear antigen) was higher in the antioxidant group. Apoptosis, measured by caspase-3, was restored to sham group levels when NAC and DFO were administered.
  
  
  
  Our experimental study showed that coadministration of NAC and DFO during liver hemorrhage can decrease the amounts of fluids needed for resuscitation. Moreover, the antioxidant combination restores the energy dependent apoptosis and proliferation of the hepatocytes.
authors.affiliation: From the 4th Department of Surgery (N.F.O., A.I.M., E.D.L., V.E.S., N.F.A.), "Attikon" University Hospital of Athens, Haidari, Greece ; Department of Anesthesia (I.I.K.), Pentelis Children's Hospital, Penteli, Greece; Department of Clinical Biochemistry (I.P.S., C.D.), "Attikon" University Hospital of Athens, Haidari, Greece; Experimental-Research Center, ELPEN Pharmaceuticals (A.E.P.), Pikermi, Greece; Department of Pathology (A.I.K.P.), "Areteion", University Hospital of Athens, Haidari, Greece.
authors.forename: Nikolaos F
authors.initials: NF
authors.lastname: Orfanos
authors.forename: Anastasios I
authors.initials: AI
authors.lastname: Mylonas
authors.forename: Iosifina I
authors.initials: II
authors.lastname: Karmaniolou
authors.forename: Irene P
authors.initials: IP
authors.lastname: Stergiou
authors.forename: Evangelos D
authors.initials: ED
authors.lastname: Lolis
authors.forename: Cleanthi
authors.initials: C
authors.lastname: Dimas
authors.forename: Apostolos E
authors.initials: AE
authors.lastname: Papalois
authors.forename: Agathi I
authors.initials: AI
authors.lastname: Kondi-Pafiti
authors.forename: Vasileios E
authors.initials: VE
authors.lastname: Smyrniotis
authors.forename: Nikolaos F
authors.initials: NF
authors.lastname: Arkadopoulos
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D000077324:Crystalloid Solutions; D003676:Deferoxamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006498:Hepatectomy; D007150:Immunohistochemistry; D007552:Isotonic Solutions / Q000494:pharmacology; D008099:Liver / Q000098:blood supply*; D008297:Male; D011897:Random Allocation; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D013552:Swine
chemical_list: D000975:Antioxidants; D000077324:Crystalloid Solutions; D007552:Isotonic Solutions; D003676:Deferoxamine; D000111:Acetylcysteine