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

Abstract

IntroductionWe 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.MethodsIn 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).ResultsDespite 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.ConclusionsDuring 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.

Protection of cerebral microcirculation, mitochondrial function, and electrocortical activity by small-volume resuscitation with terlipressin in a rat model of haemorrhagic shock

“…Small volume resuscitation has been proposed to avoid tissue oedema resulting from aggressive fluid resuscitation. 29 Indeed, animal models of haemorrhage have demonstrated that terlipressin can restore cerebral perfusion pressure without increasing intracranial pressure, 17 namely conditions required for an adequate microcirculation. An alternative approach has been to provide perfusion by small-volume isotonic fluid such as LR in combination with terlipressin, which results in a more sustained improvement in arterial pressure.…”

“…3,13 Terlipressin, a synthetic analogue of vasopressin, has been proposed for the treatment of haemorrhagic shock, 14,15 and compared with vasopressin, it is longer acting and has higher selectivity for the vasopressin V 1 receptor. 15,16 Although studies in models of haemorrhage have demonstrated that terlipressin can improve cerebral perfusion pressure and tissue oxygenation, 12,17 the efficacy in protecting brain microcirculatory, mitochondrial, and electrophysiological function is unknown. We therefore used confocal imaging to study the circulation and metabolic state of the brain during shock in vivo, and in real time.…”

Terlipressin‐induced modifications of Doppler ultrasound signals of systemic arteries in preterm infants with vasoactive‐resistant patent ductus arteriosus: A pilot study

“…This hypothesis seems to be confirmed by the shifts of the mean cerebral blood flow velocity after TP, which were significantly dependent on the previous vasoactive support (Figure ). TP‐induced improvement of cerebral perfusion may have been determined, at least in part, by the dilation of cerebral arteries through the V2‐R stimulation …”

“…TP-induced improvement of cerebral perfusion may have been determined, at least in part, by the dilation of cerebral arteries through the V2-R stimulation. 35,36 TP administered by continuous infusion was overall well tolerated. We opted to start TP administration with an initial bolus delivered in 1 hour because it seems to speed its positive effects on renal blood flow.…”

The blood-saving effect of vasopressinergic V1 receptor agonists in urologic oncology

“…В настоящее время описан положительный опыт применения данной группы препаратов для кровосбе-режения в хирургии органов желудочно-кишечного тракта, при гепаторенальном синдроме, портальной гипертензии и хирургических вмешательствах на ма-гистральных артериях малого таза [9][10][11][12][13][14].…”