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

Ida KK, Otsuki DA, Sasaki AT, Borges ES, Castro LU, Sanches TR, Shimizu MH, Andrade LC, Auler JO, Dyson A, Smith KJ, Rocha Filho JA, Malbouisson LM - Crit Care (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

ABSTRACT

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.

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Related in: MedlinePlus

Effects of terlipressin and lactated Ringer’s solution in a porcine model of haemorrhagic shock. LR, Rats treated with lactated Ringer’s solution after haemorrhagic shock; TERLI, Rats treated with terlipressin after haemorrhagic shock; HAEMO, Non-treated rats; Sham, Rats not subjected to bleeding; PbtO2, Brain tissue oxygen tension; CPP, Cerebral perfusion pressure; ICP, Intracranial pressure; MAP, Mean arterial pressure; HR, Heart rate; CI, Cardiac index; SRVI, Systemic resistance vascular index; Hb, Arterial haemoglobin level; O2ER, Oxygen extraction ratio; SvO2, Mixed venous oxygen saturation; BE, Base excess. Data are expressed as mean ± standard error. *P <0.05 versus sham group. †P <0.05 versus HAEMO group. ‡P <0.05 versus LR group.
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Fig2: Effects of terlipressin and lactated Ringer’s solution in a porcine model of haemorrhagic shock. LR, Rats treated with lactated Ringer’s solution after haemorrhagic shock; TERLI, Rats treated with terlipressin after haemorrhagic shock; HAEMO, Non-treated rats; Sham, Rats not subjected to bleeding; PbtO2, Brain tissue oxygen tension; CPP, Cerebral perfusion pressure; ICP, Intracranial pressure; MAP, Mean arterial pressure; HR, Heart rate; CI, Cardiac index; SRVI, Systemic resistance vascular index; Hb, Arterial haemoglobin level; O2ER, Oxygen extraction ratio; SvO2, Mixed venous oxygen saturation; BE, Base excess. Data are expressed as mean ± standard error. *P <0.05 versus sham group. †P <0.05 versus HAEMO group. ‡P <0.05 versus LR group.

Mentions: HR was significantly increased in the HAEMO, LR and TERLI groups from the time of shock to T120 compared with the sham group (P <0.001). From T30 to T120, HR was significantly lower in the LR group than in the HAEMO group (P <0.05) (Figure 2). MAP was significantly decreased at shock in all study groups compared with the sham group (P <0.001). In the HAEMO group, the MAP was significantly decreased from T5 to T120 compared with the other groups (P <0.001). Compared with sham animals, MAP was significantly decreased at T60, T90 and T120 in the LR group (P <0.001) and at T5 in the TERLI group (P <0.001). No significant differences in this variable were observed from T30 to T120 between the LR and TERLI groups (Figure 2). The CI was significantly decreased from T5 to T120 in the HAEMO and TERLI groups compared with the sham group (P <0.01). At the corresponding time points, the CI was significantly higher in the TERLI group than in the HAEMO group (P <0.05). In the LR group, CI was higher than in the HAEMO and TERLI groups (P <0.05) (Figure 2).Figure 2


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

Ida KK, Otsuki DA, Sasaki AT, Borges ES, Castro LU, Sanches TR, Shimizu MH, Andrade LC, Auler JO, Dyson A, Smith KJ, Rocha Filho JA, Malbouisson LM - Crit Care (2015)

Effects of terlipressin and lactated Ringer’s solution in a porcine model of haemorrhagic shock. LR, Rats treated with lactated Ringer’s solution after haemorrhagic shock; TERLI, Rats treated with terlipressin after haemorrhagic shock; HAEMO, Non-treated rats; Sham, Rats not subjected to bleeding; PbtO2, Brain tissue oxygen tension; CPP, Cerebral perfusion pressure; ICP, Intracranial pressure; MAP, Mean arterial pressure; HR, Heart rate; CI, Cardiac index; SRVI, Systemic resistance vascular index; Hb, Arterial haemoglobin level; O2ER, Oxygen extraction ratio; SvO2, Mixed venous oxygen saturation; BE, Base excess. Data are expressed as mean ± standard error. *P <0.05 versus sham group. †P <0.05 versus HAEMO group. ‡P <0.05 versus LR group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4373118&req=5

Fig2: Effects of terlipressin and lactated Ringer’s solution in a porcine model of haemorrhagic shock. LR, Rats treated with lactated Ringer’s solution after haemorrhagic shock; TERLI, Rats treated with terlipressin after haemorrhagic shock; HAEMO, Non-treated rats; Sham, Rats not subjected to bleeding; PbtO2, Brain tissue oxygen tension; CPP, Cerebral perfusion pressure; ICP, Intracranial pressure; MAP, Mean arterial pressure; HR, Heart rate; CI, Cardiac index; SRVI, Systemic resistance vascular index; Hb, Arterial haemoglobin level; O2ER, Oxygen extraction ratio; SvO2, Mixed venous oxygen saturation; BE, Base excess. Data are expressed as mean ± standard error. *P <0.05 versus sham group. †P <0.05 versus HAEMO group. ‡P <0.05 versus LR group.
Mentions: HR was significantly increased in the HAEMO, LR and TERLI groups from the time of shock to T120 compared with the sham group (P <0.001). From T30 to T120, HR was significantly lower in the LR group than in the HAEMO group (P <0.05) (Figure 2). MAP was significantly decreased at shock in all study groups compared with the sham group (P <0.001). In the HAEMO group, the MAP was significantly decreased from T5 to T120 compared with the other groups (P <0.001). Compared with sham animals, MAP was significantly decreased at T60, T90 and T120 in the LR group (P <0.001) and at T5 in the TERLI group (P <0.001). No significant differences in this variable were observed from T30 to T120 between the LR and TERLI groups (Figure 2). The CI was significantly decreased from T5 to T120 in the HAEMO and TERLI groups compared with the sham group (P <0.01). At the corresponding time points, the CI was significantly higher in the TERLI group than in the HAEMO group (P <0.05). In the LR group, CI was higher than in the HAEMO and TERLI groups (P <0.05) (Figure 2).Figure 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus