Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock

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• 作者：Keila Kazue Ida (1) (2)
  Denise Aya Otsuki (1)
  Adolfo Toshiro Cotarelli Sasaki (1)
  Emilyn Silva Borges (1)
  Let铆cia Urbano Cardoso Castro (3)
  Talita Rojas Sanches (3)
  Maria-Heloisa Massola Shimizu (3)
  L煤cia Concei莽茫o Andrade (3)
  Jos茅-Ot谩vio Costa Auler Jr (1)
  Alex Dyson (4)
  Kenneth John Smith (2)
  Joel Avancini Rocha Filho (5)
  Luiz-Marcelo S谩 Malbouisson (1)
  
  1. Laborat贸rio de Investiga莽茫o M茅dica (LIM-08) ; Disciplina de Anestesiologia ; Faculdade de Medicina ; Universidade de S茫o Paulo ; Avenida Doutor Arnaldo ; 455 ; 2掳 andar ; sala 2120 ; Cerqueira C茅sar ; S茫o Paulo ; SP ; 01246-903 ; Brazil
  2. Department of Neuroinflammation ; Institute of Neurology ; University College London (UCL) ; 1 Wakefield Street ; 2nd floor ; WC1N 1PJ ; London ; UK
  3. Disciplina de Nefrologia ; Faculdade de Medicina ; Universidade de S茫o Paulo (LIM-12 HC-FMUSP) ; Avenida Doutor Arnaldo ; 455 ; 3rd floor ; Cerqueira C茅sar ; S茫o Paulo ; SP ; 01246-903 ; Brazil
  4. Division of Medicine ; University College London (UCL) ; Gower Street ; WC1E 6BT ; London ; UK
  5. Divis茫o de Anestesiologia ; Hospital das Cl铆nicas da Faculdade de Medicina da Universidade de S茫o Paulo (HCFMUSP) ; Av. Dr. En茅as de Carvalho Aguiar ; 155 ; 8th floor ; 05403-000 ; S茫o Paulo ; SP ; Brazil
  
• 刊名：Critical Care
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：19
• 期：1
• 全文大小：1,567 KB
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• 刊物主题：Intensive / Critical Care Medicine; Emergency Medicine;
• 出版者：BioMed Central
• ISSN：1364-8535

文摘

Introduction 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聽mmHg for 30聽minutes) were randomised to receive lactated Ringer鈥檚 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聽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鈭?/sup> 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.