Impact of fluid therapy on apoptosis and organ injury during haemorrhagic shock in an oxygen-debt-controlled pig model

Apoptosis, or programmed cell death, seems to play a role in the physiology of shock. The influence of fluid resuscitation on the occurrence of apoptosis during haemorrhage is still unclear. Using an experimental randomised study, the goal of this investigation was to find a relation between different frequently used resuscitation fluids and evidence of apoptosis.

Sixty female pigs with a mean body weight of 20 kg were randomised into six groups, each receiving a different resuscitation fluid therapy: malated Ringer, lactated Ringer, hypertonic saline, hypertonic saline solution/Dextran 60, carbonate/gelatine and a sham group (no shock, no resuscitation). A haemorrhagic shock with a predefined oxygen debt with high mortality expected was induced for a period of 60 min. Then, the resuscitation fluid therapy within each group was initiated. At the beginning, after 1 h of shock and 1 and 2 h after resuscitation, biopsies from the liver were taken, as one of the most important metabolism organs of shock. Three hours after the beginning of the resuscitation period, the animals were allowed to recover under observation for 3 days. At the end of this period, a state of narcosis was induced and another liver biopsy was taken. Finally, the animals were sacrificed and samples were taken from the liver, kidney, heart and hippocampus. The TUNEL method was used for identifying apoptosis. Impairment of liver function was indicated by the measurement of transaminase levels.

There was no observed difference in the rate of apoptosis in all groups and a low number of apoptotic cells were found in all the organs sampled. The sham group also showed a low count of apoptosis. The hypoxia-sensitive neurons within the hippocampus did not show any signs of apoptosis. The high oxygen debt during haemorrhage led to a high mortality. The non-treated animals died very quickly, as an indicator for severe shock. Animals treated with hypertonic saline showed a significant increase in aspartate transaminase (AST) plasma levels on the first day after shock.

The different resuscitation fluids used in the treatment of haemorrhagic shock in this experimental model showed no evidence of a different apoptosis rate in the end organs.