Comparison of the effects of lactated Ringer\'s solution, hypertonic saline solution and terlipressin resuscitation on cerebral tissue oxygenation and perfusion in an experimental model of haemorrhagic shock

Author(s)

Keila Kazue Ida

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2015-06-15

Examining board members

Luiz Marcelo Sá Malbouisson

• Advisor: Luiz Marcelo Sá Malbouisson

Abstract

INTRODUCTION: Small-volume resuscitation with hypertonic saline solution (HSS) or terlipressin can be an alternative to the administration of large amounts of crystalloids in haemorrhagic shock. The aim of this study was to evaluate the effects of HSS and terlipressin on cerebral perfusion and oxygenation and investigate the cerebral mechanisms associated with microcirculation, mitochondrial function, electrocortical activity and apoptotic pathways during haemorrhagic shock. METHODS: Isoflurane-anaesthetised animals were submitted to haemorrhagic shock [Haemo group; mean arterial pressure (MAP) of 40 mmHg for 30 minutes] and treated with lactated Ringer\'s solution (LR) (3LR group; 3x volume bled), terlipressin (Terli group; bolus) or HSS (HSS group; bolus 4 mL/kg) and were compared with a Sham group. A porcine model (n = 56) was used to assess the cerebral perfusion pressure (CPP) and tissue oxygenation (PbtO2) and the expression of tissue markers of water (aquaporin-4), sodium (Na-K-2Cl cotransporter-1), oxidative stress (thiobarbituric acid reactive substances and manganese superoxide dismutase) and apoptosis in cerebral samples. A murine model (n = 179) was used to assess microcirculation (FITC-dextran fluorescence) and mitochondrial function (redox and membrane potential, using the fluorescence of endogenous flavoproteins and tetramethylrhodamine methyl ester, respectively) in the cerebral cortex by using in vivo confocal microscopy, and to assess the electrocortical brain activity by monitoring the somatosensory evoked potential. In the murine model, three additional groups were evaluated, which received terlipressin associated to LR (1x, 2x or 3x blood withdrawn). RESULTS: In the porcine Hemo group, there was a significant decrease in the CPP and PbtO2, which were associated to an increased cerebral expression of markers of water and sodium transport, oxidative stress and apoptosis compared with Sham. In the murine model, the haemorrhagic shock-induced hypotension was correlated to a decrease in the cortical vascular density and to dysfunctions on brain mitochondria and electrocortical activity. In the porcine 3LR group, the infusion of large volumes of LR recovered the PbtO2, but not the CPP, and was accompanied by an increased cerebral expression of markers of water and sodium transport, oxidative stress and apoptosis compared with Sham. In the rats, the aggressive fluid resuscitation did not recover the cortical vascular density, which was correlated to the brain mitochondrial and electrocortical dysfunctions. In the porcine Terli group, the increase in the MAP was associated with the recovery of CPP, PbtO2, and expression of markers of water and sodium regulation, oxidative stress and apoptosis within the brain. In the rats treated with terlipressin, associated or not with 1x or 2x LR, there was a positive correlation between the recovery of the cortical vascular density and the recovery of the brain mitochondrial and electrocortical functions. Such improvements were not observed in none of the models treated with HSS. CONCLUSIONS: LR and terlipressin recovered tissue oxygenation in the cerebral cortex, but only terlipressin recovered the cerebral perfusion, reversing the brain mitochondrial and electrocortical dysfunctions and the increase in the markers of water and sodium transport, oxidative stress, and apoptosis induced by haemorrhagic shock. The HSS did not recover cerebral perfusion and oxygenation (AU)

• FAPESP's process: 11/14386-2 - Comparison of resuscitation effects of Ringer lactate, hypertonic saline solution and terlipressin on cerebral perfusion and oxygenation in an experimental model of hemorrhagic shock
• Grantee: Keila Kazue Ida
• Support Opportunities: Scholarships in Brazil - Doctorate