Abstract / Summary
Abstract We have previously shown that fresh frozen plasma (FFP) and fibrinogen have protective effects in mice with hemorrhagic shock through restoration of endothelial syndecan-1 and reversal of endothelial injury. In the current study, we tested the hypothesis that a combined model of abdominal sepsis and hemorrhagic shock would induce endothelial syndecan-1 shedding and lung injury which could be attenuated by both FFP and fibrinogen. C57BL/6 mice underwent cecal ligation and puncture (CLP) followed by hemorrhagic shock (HS) and fluid resuscitation with lactated Ringer’s (LR), fibrinogen (5 mg/mouse), and FFP, all at 1X shed blood volume. After 24 h, lung tissues and plasma were harvested for assays. CLP + HS induced an increase in alveolar thickness and decreases in lung syndecan-1 and lung neutrophil granule-enzymes (myeloperoxidase, neutrophil elastase, and MMP9), with reciprocal elevations in plasma syndecan-1 and plasma neutrophil granule-enzymes (myeloperoxidase, neutrophil elastase, and MMP9). All these alterations were significantly attenuated by FFP but not by fibrinogen. Additionally, CLP + HS-induced hypotension at 24 h was partially reversed by FFP but not by fibrinogen. Our results suggest that FFP administration was associated with inhibition of CLP + HS-induced neutrophil degranulation to prevent syndecan-1 shedding and lung injury. The present results provide preclinical evidence supporting further investigation of FFP for therapeutic use in traumatic hemorrhagic shock with sepsis.