Cargando…

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

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 control...

Descripción completa

Detalles Bibliográficos
Autores principales: Ida, Keila Kazue, Otsuki, Denise Aya, Sasaki, Adolfo Toshiro Cotarelli, Borges, Emilyn Silva, Castro, Letícia Urbano Cardoso, Sanches, Talita Rojas, Shimizu, Maria-Heloisa Massola, Andrade, Lúcia Conceição, Auler, José-Otávio Costa, Dyson, Alex, Smith, Kenneth John, Filho, Joel Avancini Rocha, Malbouisson, Luiz-Marcelo Sá
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373118/
https://www.ncbi.nlm.nih.gov/pubmed/25888229
http://dx.doi.org/10.1186/s13054-015-0825-9
_version_ 1782363295300190208
author Ida, Keila Kazue
Otsuki, Denise Aya
Sasaki, Adolfo Toshiro Cotarelli
Borges, Emilyn Silva
Castro, Letícia Urbano Cardoso
Sanches, Talita Rojas
Shimizu, Maria-Heloisa Massola
Andrade, Lúcia Conceição
Auler, José-Otávio Costa
Dyson, Alex
Smith, Kenneth John
Filho, Joel Avancini Rocha
Malbouisson, Luiz-Marcelo Sá
author_facet Ida, Keila Kazue
Otsuki, Denise Aya
Sasaki, Adolfo Toshiro Cotarelli
Borges, Emilyn Silva
Castro, Letícia Urbano Cardoso
Sanches, Talita Rojas
Shimizu, Maria-Heloisa Massola
Andrade, Lúcia Conceição
Auler, José-Otávio Costa
Dyson, Alex
Smith, Kenneth John
Filho, Joel Avancini Rocha
Malbouisson, Luiz-Marcelo Sá
author_sort Ida, Keila Kazue
collection PubMed
description 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 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.
format Online
Article
Text
id pubmed-4373118
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-43731182015-03-26 Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock Ida, Keila Kazue Otsuki, Denise Aya Sasaki, Adolfo Toshiro Cotarelli Borges, Emilyn Silva Castro, Letícia Urbano Cardoso Sanches, Talita Rojas Shimizu, Maria-Heloisa Massola Andrade, Lúcia Conceição Auler, José-Otávio Costa Dyson, Alex Smith, Kenneth John Filho, Joel Avancini Rocha Malbouisson, Luiz-Marcelo Sá Crit Care Research 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 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. BioMed Central 2015-03-13 2015 /pmc/articles/PMC4373118/ /pubmed/25888229 http://dx.doi.org/10.1186/s13054-015-0825-9 Text en © Ida et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ida, Keila Kazue
Otsuki, Denise Aya
Sasaki, Adolfo Toshiro Cotarelli
Borges, Emilyn Silva
Castro, Letícia Urbano Cardoso
Sanches, Talita Rojas
Shimizu, Maria-Heloisa Massola
Andrade, Lúcia Conceição
Auler, José-Otávio Costa
Dyson, Alex
Smith, Kenneth John
Filho, Joel Avancini Rocha
Malbouisson, Luiz-Marcelo Sá
Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock
title Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock
title_full Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock
title_fullStr Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock
title_full_unstemmed Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock
title_short Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock
title_sort effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373118/
https://www.ncbi.nlm.nih.gov/pubmed/25888229
http://dx.doi.org/10.1186/s13054-015-0825-9
work_keys_str_mv AT idakeilakazue effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT otsukideniseaya effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT sasakiadolfotoshirocotarelli effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT borgesemilynsilva effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT castroleticiaurbanocardoso effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT sanchestalitarojas effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT shimizumariaheloisamassola effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT andradeluciaconceicao effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT aulerjoseotaviocosta effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT dysonalex effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT smithkennethjohn effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT filhojoelavancinirocha effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock
AT malbouissonluizmarcelosa effectsofterlipressinasearlytreatmentforprotectionofbraininamodelofhaemorrhagicshock