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

Br J Anaesth. 2018 Jun;120(6):1245-1254. doi: 10.1016/j.bja.2017.11.074. Epub 2017 Dec 5.


Background: During early treatment of haemorrhagic shock, cerebral perfusion pressure can be restored by small-volume resuscitation with vasopressors. Whether this therapy is improved with additional fluid remains unknown. We assessed the value of terlipressin and lactated Ringer's solution (LR) on early recovery of microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex.

Methods: Animals treated with LR replacing three times (3LR) the volume bled (n=26), terlipressin (n=27), terlipressin plus 1LR (n=26), 2LR (n=16), or 3LR (n=15) were compared with untreated (n=36) and sham-operated rats (n=17). In vivo confocal microscopy was used to assess cortical capillary perfusion, changes in tissue oxygen concentration, and mitochondrial membrane potential and redox state. Electrophysiological function was assessed by cortical somatosensory evoked potentials, spinal cord dorsum potential, and peripheral electromyography.

Results: Compared with sham treatment, haemorrhagic shock reduced the mean (SD) area of perfused vessels [82% (sd 10%) vs 38% (12%); P<0.001] and impaired oxygen concentration, mitochondrial redox state [99% (4%) vs 59% (15%) of baseline; P<0.001], and somatosensory evoked potentials [97% (13%) vs 27% (19%) of baseline]. Administration of terlipressin plus 1LR or 2LR was able to recover these measures, but terlipressin plus 3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function.

Conclusions: Resuscitation from haemorrhagic shock using terlipressin with small-volume LR was superior to high-volume LR, with regard to cerebral microcirculation, and mitochondrial and electrophysiological functions.

Keywords: brain ischaemia; confocal microscopy; electrophysiology.

MeSH terms

  • Animals
  • Cerebral Cortex / blood supply
  • Cerebrovascular Circulation / drug effects*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Fluid Therapy / methods*
  • Kaplan-Meier Estimate
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / physiology
  • Microcirculation / drug effects
  • Microscopy, Confocal
  • Mitochondria / metabolism
  • Oxidation-Reduction
  • Oxygen Consumption / drug effects
  • Random Allocation
  • Rats, Sprague-Dawley
  • Ringer's Lactate / pharmacology
  • Ringer's Lactate / therapeutic use
  • Shock, Hemorrhagic / physiopathology
  • Shock, Hemorrhagic / therapy*
  • Terlipressin / pharmacology
  • Terlipressin / therapeutic use*
  • Vasoconstrictor Agents / pharmacology
  • Vasoconstrictor Agents / therapeutic use*


  • Ringer's Lactate
  • Vasoconstrictor Agents
  • Terlipressin