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

Abstract

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 the early recovery of the microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex. Methods Animals treated with LR replacing three times (3x) the volume bled (n=26), terlipressin (n=27), terlipressin plus LR of 1x (n=26), 2x (n=16), or 3x (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 (SEPs), spinal cord dorsum potential, and peripheral electromyography. Results Compared with sham, the mean (SD) area of perfused vessels was lower in rats subjected to haemorrhagic shock: 82 (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 SEPs (97±13% vs. 27±19% of baseline). Adminstration of terlipressin plus 1X or 2X LR was able to recover these measures, but terlipressin+3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function. Conclusion 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 function