title: Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock.
abstract: BACKGROUND
  We investigated whether treatment with terlipressin during recovery from hypotension due to haemorrhagic shock (HS) is effective in restoring cerebral perfusion pressure (CPP) and brain tissue markers of water balance, oxidative stress and apoptosis.
  
  
  METHODS
  In this randomised controlled study, animals undergoing HS (target mean arterial pressure (MAP) 40 mmHg for 30 minutes) were randomised to receive lactated Ringer's solution (LR group; n =14; volume equal to three times the volume bled), terlipressin (TERLI group; n =14; 2-mg bolus), no treatment (HAEMO group; n =12) or sham (n =6). CPP, systemic haemodynamics (thermodilution technique) and blood gas analyses were registered at baseline, shock and 5, 30, 60 (T60), 90 and 120 minutes after treatment (T120). After the animals were killed, brain tissue samples were obtained to measure markers of water balance (aquaporin-4 (AQP4)), Na(+)-K(+)-2Cl(-) co-transporter (NKCC1)), oxidative stress (thiobarbituric acid reactive substances (TBARS) and manganese superoxide dismutase (MnSOD)) and apoptotic damage (Bcl-x and Bax).
  
  
  RESULTS
  Despite the HS-induced decrease in cardiac output (CO) and hyperlactataemia, resuscitation with terlipressin recovered MAP and resulted in restoration of CPP and in cerebral protection expressed by normalisation of AQP4, NKCC1, TBARS and MnSOD expression and Bcl-x/Bax ratio at T60 and T120 compared with sham animals. In the LR group, CO and blood lactate levels were recovered, but the CPP and MAP were significantly decreased and TBARS levels and AQP4, NKCC1 and MnSOD expression and Bcl-x/Bax ratio were significantly increased at T60 and T120 compared with the sham group.
  
  
  CONCLUSIONS
  During recovery from HS-induced hypotension, terlipressin was effective in normalising CPP and cerebral markers of water balance, oxidative damage and apoptosis. The role of this pressor agent on brain perfusion in HS requires further investigation.
authors.affiliation: Laboratório de Investigação Médica (LIM-08), Disciplina de Anestesiologia, Faculdade de Medicina, Universidade de São Paulo, Avenida Doutor Arnaldo, 455, 2° andar, sala 2120, Cerqueira César, São Paulo, SP, 01246-903, Brazil. keilaida@usp.br.|Department of Neuroinflammation, Institute of Neurology, University College London (UCL), 1 Wakefield Street, 2nd floor, WC1N 1PJ, London, UK. keilaida@usp.br.
authors.forename: Keila Kazue
authors.initials: KK
authors.lastname: Ida
authors.affiliation: Laboratório de Investigação Médica (LIM-08), Disciplina de Anestesiologia, Faculdade de Medicina, Universidade de São Paulo, Avenida Doutor Arnaldo, 455, 2° andar, sala 2120, Cerqueira César, São Paulo, SP, 01246-903, Brazil. lim08@usp.br.
authors.forename: Denise Aya
authors.initials: DA
authors.lastname: Otsuki
authors.affiliation: Laboratório de Investigação Médica (LIM-08), Disciplina de Anestesiologia, Faculdade de Medicina, Universidade de São Paulo, Avenida Doutor Arnaldo, 455, 2° andar, sala 2120, Cerqueira César, São Paulo, SP, 01246-903, Brazil. atcsasaki@gmail.com.
authors.forename: Adolfo Toshiro Cotarelli
authors.initials: AT
authors.lastname: Sasaki
authors.affiliation: Laboratório de Investigação Médica (LIM-08), Disciplina de Anestesiologia, Faculdade de Medicina, Universidade de São Paulo, Avenida Doutor Arnaldo, 455, 2° andar, sala 2120, Cerqueira César, São Paulo, SP, 01246-903, Brazil. emilynborges@gmail.com.
authors.forename: Emilyn Silva
authors.initials: ES
authors.lastname: Borges
authors.affiliation: Disciplina de Nefrologia, Faculdade de Medicina, Universidade de São Paulo (LIM-12 HC-FMUSP), Avenida Doutor Arnaldo, 455, 3rd floor, Cerqueira César, São Paulo, SP, 01246-903, Brazil. letiurbano@yahoo.com.br.
authors.forename: Letícia Urbano Cardoso
authors.initials: LU
authors.lastname: Castro
authors.affiliation: Disciplina de Nefrologia, Faculdade de Medicina, Universidade de São Paulo (LIM-12 HC-FMUSP), Avenida Doutor Arnaldo, 455, 3rd floor, Cerqueira César, São Paulo, SP, 01246-903, Brazil. tatarojas@gmail.com.
authors.forename: Talita Rojas
authors.initials: TR
authors.lastname: Sanches
authors.affiliation: Disciplina de Nefrologia, Faculdade de Medicina, Universidade de São Paulo (LIM-12 HC-FMUSP), Avenida Doutor Arnaldo, 455, 3rd floor, Cerqueira César, São Paulo, SP, 01246-903, Brazil. hmshimizu@gmail.com.
authors.forename: Maria-Heloisa Massola
authors.initials: MH
authors.lastname: Shimizu
authors.affiliation: Disciplina de Nefrologia, Faculdade de Medicina, Universidade de São Paulo (LIM-12 HC-FMUSP), Avenida Doutor Arnaldo, 455, 3rd floor, Cerqueira César, São Paulo, SP, 01246-903, Brazil. luciacan@usp.br.
authors.forename: Lúcia Conceição
authors.initials: LC
authors.lastname: Andrade
authors.affiliation: Laboratório de Investigação Médica (LIM-08), Disciplina de Anestesiologia, Faculdade de Medicina, Universidade de São Paulo, Avenida Doutor Arnaldo, 455, 2° andar, sala 2120, Cerqueira César, São Paulo, SP, 01246-903, Brazil. auler.junior@diretoria.fm.usp.br.
authors.forename: José-Otávio Costa
authors.initials: JO
authors.lastname: Auler
authors.affiliation: Division of Medicine, University College London (UCL), Gower Street, WC1E 6BT, London, UK. a.dyson@ucl.ac.uk.
authors.forename: Alex
authors.initials: A
authors.lastname: Dyson
authors.affiliation: Department of Neuroinflammation, Institute of Neurology, University College London (UCL), 1 Wakefield Street, 2nd floor, WC1N 1PJ, London, UK. k.smith@ucl.ac.uk.
authors.forename: Kenneth John
authors.initials: KJ
authors.lastname: Smith
authors.affiliation: Divisão de Anestesiologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Av. Dr. Enéas de Carvalho Aguiar,155, 8th floor, 05403-000, São Paulo, SP, Brazil. joelrocha@me.com.
authors.forename: Joel Avancini
authors.initials: JA
authors.lastname: Rocha Filho
authors.affiliation: Laboratório de Investigação Médica (LIM-08), Disciplina de Anestesiologia, Faculdade de Medicina, Universidade de São Paulo, Avenida Doutor Arnaldo, 455, 2° andar, sala 2120, Cerqueira César, São Paulo, SP, 01246-903, Brazil. luiz.malbouisson@hc.fm.usp.br.
authors.forename: Luiz-Marcelo Sá
authors.initials: LM
authors.lastname: Malbouisson
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D005440:Fluid Therapy; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000188:drug therapy* / Q000209:etiology; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy*; D013552:Swine; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin