The Journal of surgical research
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Gelsolin is a plasma protein that functions to depolymerize actin filaments preventing capillary plug formation following tissue injury. It also functions to mediate the inflammatory response by binding proinflammatory lipids such as lysophosphatidic acid, sphingosine-1-phosphate and phosphoinositides. Clinically, reduced gelsolin concentrations have been associated with increased mortality in critically ill, trauma, and burn patients. We have previously shown that following hemorrhagic shock with splanchnic hypoperfusion, mesenteric lymph contains lipid components that cause neutrophil and EC activation and that protein concentrations are severely diluted due to resuscitation. We hypothesized that lipid binding proteins such as gelsolin may be depleted after trauma/hemorrhagic shock leading to increased lipid bioactivity. ⋯ Gelsolin is found at high levels (comparable to plasma) in mesenteric lymph. Following hemorrhagic shock, gelsolin levels decrease significantly, possibly due to consumption by the actin scavenging system. The magnitude of this change in concentration could release lipid bioactivity and predispose the lung and other organs to capillary injury.
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Evidence exists that resuscitation with Ringer's lactate (RL) contributes to postshock inflammation and lung injury. We hypothesized that the anti-inflammatory agent pentoxifylline (PTX) attenuates postresuscitative lung injury through modulation of transcription factors after hemorrhagic shock. ⋯ The addition of PTX to conventional RL infusion after shock significantly reduced histological lung injury and pulmonary neutrophil activity when compared to treatment with RL alone. The administration of PTX was also associated with diminished NF-kappaB and enhanced CREB activation. Therefore, the administration of PTX may serve as a novel therapeutic adjunct after hemorrhagic shock.