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

Keila Kazue Ida, Denise Aya Otsuki, Adolfo Toshiro Cotarelli Sasaki, Emilyn Silva Borges, Letícia Urbano Cardoso Castro, Talita Rojas Sanches, Maria-Heloisa Massola Shimizu, Lúcia Conceição Andrade, José-Otávio Costa Auler, Alex Dyson, Kenneth John Smith, Joel Avancini Rocha Filho, Luiz-Marcelo Sá Malbouisson

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. 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). 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. 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.