Effect of different resuscitation strategies on neutrophil activation in a swine model of hemorrhagic shock

Activated neutrophils play a pivotal role in resuscitation injury. The strategies used for resuscitation (types of fluids and methods of administration) can affect the degree of neutrophil activation. The aim of this study was to test the commonly available resuscitation fluids in a large animal model of hemorrhagic shock to determine the strategy associated with the least degree of neutrophil activation. Methods: Female swine (n=63, weight 45-60 kg) were anesthetized using isoflurane and catheters were placed for hemodynamic monitoring. After 120 min, they were subjected to a volume controlled hemorrhage (28 ml/kg) over 15 min, kept in shock for 60 min, and then resuscitated. The resuscitation groups were as follows: (1) anesthesia only (n=5); (2) hemorrhage, sham resuscitation (n=5); (3) LR-fast rate 3× blood loss (n=6); (4) LR slow rate-3× blood loss (n=6); (5) LR low volume-1× blood loss (n=6); (6) Dextran 40-1× blood loss (n=6); (7) 6% hetastarch-1× blood loss (n=6); (8) 5% albumin-1× blood loss (n=6); (9) 25% albumin-1/5× blood loss (n=6); (10) whole blood resuscitation-1× blood loss (n=6); (11) 7.5% hypertonic saline (HTS)-0.3× blood loss (n=5). Resuscitation fluids were infused over 1 h in all groups except group 4 (LR slow rate, which was over 3 h). Animals were observed for 180 min following the resuscitation period. Neutrophil oxidative burst activity was determined in whole blood using flow cytometery. Results: Animals resuscitated with dextran and hetastarch showed significantly (P<0.05) higher neutrophil burst activity. Resuscitation with LR also caused neutrophil activation (P<0.05), and the highest degree of activation was seen when a large volume of LR was given at a fast rate (group 8). However, all LR infusion protocols were associated with significant neutrophil activation compared with anesthesia (group 1) or sham resuscitation (group 2). No significant activation was seen in the animals resuscitated with albumin or fresh whole blood. Conclusion: Artificial colloids and LR (independent of rate or volume of infusion) caused significant neutrophil activation, which was not seen with albumin and whole blood resuscitation. These findings suggest that the type of resuscitation fluid and method of infusion can influence neutrophil function.