Albumin protects against gut-induced lung injury in vitro and in vivo

Objective: Since albumin has the ability to detoxify, we assessed whether low-dose albumin could protect against trauma/hemorrhagic shock (T/HS)-induced endothelial cell, lung, gut, and red blood cell (RBC) injury in vivo and endothelial cell injury in vitro. Summary Background Data: T/HS cause ischemic insult to the gut, resulting in the release of biologically active factors into the mesenteric lymph, which then cause injury to multiple distant organs. Methods: In vitro experiments tested the ability of albumin to reduce the cytotoxicity of mesenteric lymph from male rats subjected to T/HS (laparotomy + MAP 30 rum Hg for 90 minutes) for human umbilical vein endothelial cell (HUVEC). In subsequent in vivo experiments, the ability of albumin given as part of the resuscitation regimen to protect against T/HS-induced injury was tested by comparing the magnitude of injury in T/HS rats receiving human albumin (shed blood + 0.12, 0.24, or 0.36 g/kg) or lactated Ringer's solution (shed blood + 2 x volume of shed blood as LR) with that observed in rats subjected to trauma/sham shock. Rats were killed after a 3-hour recovery period and had lung permeability evaluated by bronchoalveolar lavage and myeloperoxidase assays, intestinal microvillous injury by histology, and RBC deformability using ektacytometry. Results: Both bovine and human albumin prevented T/HS lymph-induced HUVEC cytotoxicity in vitro, even when added 30 minutes after the lymph (viability 15 +/- 4% to 88 +/- 3%, P < 0.01). In vivo RBC deformability was better preserved by blood plus albumin than blood plus lactated Ringer's solution (P < 0.01). Likewise, albumin administration reduced T/HS-induced lung permeability and neutrophil sequestration in a dose-dependent fashion, with 0.36 g/kg of albumin effecting total lung protection (P < 0.01). In contrast, albumin treatment did not prevent T/HS-Conclusions: Low-dose albumin protects against gut lymph-induced lung, HUVEC, and RBC injury by neutralizing T/HS lymph toxicity.induced gut injury.