Aggressive re-warming at 38.5 °C following deep hypothermia at 21 °C increases neutrophil membrane bound elastase activity and pro-inflammatory factor release

BACKGROUND: Cardiopulmonary bypass (CPB) is often performed under hypothermic condition. The effects of hypothermia and re-warming on neutrophil activity are unclear. This study aimed to compare the effects of different hypothermia and re-warming regimens on neutrophil membrane bound elastase (MBE) activity and the release of pro-inflammatory factors from neutrophils. METHODS: Human neutrophils were exposed to different hypothermia and re-warming regimens. MBE activity and the release of interleukin (IL)-β1, IL-6, IL-8, and tumor necrosis factor (TNF)-α were measured. RESULTS: Neutrophil MBE activity was significantly reduced after 60-min moderate (28 °C) or deep (21 °C) hypothermic treatment. Compared with normothermic (37 °C) re-warming, aggressive re-warming (38.5°) for 120 min following deep hypothermia (21 °C) dramatically increased neutrophil MBE activity (P < 0.05). Co-incubation of neutrophils with platelet-rich plasma further increased MBE activity significantly under all the tested temperature regimens. IL-β1 release from neutrophils was significantly higher after deep hypothermia (21 °C) followed by normothermic (37 °C) re-warming than after moderate hypothermia (28 °C) followed by normothermic re-warming (P < 0.05). Aggressive re-warming (38.5°) following deep hypothermia significantly increased the release of IL-β1, IL-8, and TNF-α from neutrophil compared with moderate re-warming (37 °C) (all P < 0.05). CONCLUSION: Aggressive re-warming following deep hypothermia may contribute to CPB-associated tissue injury by increasing neutrophil MBE activity and stimulating pro-inflammatory factor release, thus, should be avoided. The optimal hypothermic temperature of CPB should be determined based on patient clinical characteristics and surgery type.