Treatment with fibrinogen γ-chain peptide-coated, adenosine 5'-diphosphate-encapsulated liposomes as an infusible hemostatic agent against active liver bleeding in rabbits with acute thrombocytopenia.

BACKGROUND: We evaluated the hemostatic efficacy of H12-(adenosine 5'-diphosphate [ADP])-liposomes in the setting of active liver bleeding in rabbits with dilutional thrombocytopenia after massive transfusion. STUDY DESIGN AND METHODS: Acute thrombocytopenia (platelet [PLT] count < 50 × 10(9) /L) was induced in rabbits by repeated blood withdrawal and isovolemic transfusion of autologous washed red blood cells. Liver hemorrhage was initiated by a penetrating liver injury. Subsequently, the animals received tamponade treatment for the liver hemorrhage for 5 minutes and were intravenously administered H12-(ADP)-liposomes with PLT-poor plasma (PPP), PLT-rich plasma (PRP), PPP alone, H12-(phosphate-buffered saline [PBS])-liposome/PPP, or H12-(ADP)-liposomes/PPP plus fibrinogen concentrate during the tamponade. RESULTS: Administration of H12-(ADP)-liposomes/PPP rescued 60% of the rabbits from the liver hemorrhage; PRP administration rescued 50%. In contrast, rabbits receiving PPP or H12-(PBS)-liposome/PPP achieved only 10 or 17% survival, respectively, for the first 24 hours. H12-(ADP)-liposomes/PPP as well as PRP consistently reduced bleeding volumes and shortened clotting times (CTs) in comparison to PPP administration. Specifically, bleeding volumes in the initial 5 minutes averaged 11 mL (H12-(ADP)-liposomes/PPP) and 17 mL (PRP) versus 30 mL (PPP; p < 0.05); CTs averaged 270 and 306 seconds versus 401 seconds (p < 0.05). H12-(ADP)-liposomes were observed at the bleeding site with thrombus formation, suggesting an induction of thrombi. Neither macro- nor microthrombi were detected in the lung, kidney, spleen, or liver in rabbits treated with H12-(ADP)-liposomes. Supplementation of fibrinogen to H12-(ADP)-liposomes/PPP did not significantly improve rabbit survival. CONCLUSIONS: H12-(ADP)-liposomes might be a safe and effective therapeutic tool during damage control surgery for trauma patients with acute thrombocytopenia and massive bleeding.

Influence of fish to soybean oil ratio on hepatic mononuclear cell function and survival after intraportal bacterial challenge in parenterally fed mice.

BACKGROUND: Parenteral nutrition (PN) is indispensable for meeting the caloric and substrate needs of patients who cannot receive adequate amounts of enteral nutrition. However, PN decreases hepatic mononuclear cell (MNC) numbers and impairs their functions. We examined the effects of various ratios of ω-3 to ω-6 polyunsaturated fatty acids on hepatic MNC number and function in a murine model. We focused on serum liver enzymes, lipid metabolism, cytokine production, histopathology, and the outcomes of an intraportal bacterial challenge. MATERIAL AND METHODS: In experiment 1, male Institute of Cancer Research mice were randomized to CHOW, 67%, 33%, 16%, 8%, 4%, and 0% fish oil (FO)-PN groups. After receiving their respective diets for 5 days, 1.0 × 10(7) Pseudomonas aeruginosa were delivered by intraportal injection. Survival was observed ≤ 7 days after injection. Liver histologies after intraportal bacterial challenge were examined in the CHOW, 33%, 8%, and 0% FO-PN groups. In experiment 2, the mice were divided into 4 groups: CHOW, 33%, 8%, and 0% FO-PN. After the mice had been fed for 5 days, MNC were isolated. Hepatic MNC were counted and cytokine productions (tumor necrosis factor [TNF]-α and interleukin [IL]-10) by MNC in response to lipopolysaccharide (LPS) were measured. Blood samples were analyzed for lipid metabolism and hepatobiliary biochemical parameters. Liver histologies were also examined. RESULTS: In experiment 1, survival times were significantly shorter in the 4% and 0% FO-PN groups than in the CHOW group. Survival rates at 168 hours were 100%, 64%, 86%, 73%, 67%, 11%, and 13% in the CHOW, 67%, 33%, 16%, 8%, 4%, and 0% FO-PN groups, respectively. At 72 hours after intraportal bacterial challenge, the 0% FO-PN group showed severe tissue damage, whereas such damage was reduced in the 8% and 33% FO-PN groups. In experiment 2, the CHOW, 33%, 8%, and 0% FO-PN groups showed LPS dose-dependent increases in TNF-α levels. IL-10 levels were also LPS dose-dependently increased in the CHOW and 33% FO-PN groups. However, no marked changes were observed in response to LPS stimulation in either the 8% or the 0% FO-PN group. There were no differences in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or total bilirubin among these 4 groups. In the 0% FO-PN group, serum total cholesterol levels were greater than those in the 8% and 33% FO-PN groups. Without bacterial challenge, livers from the 0% FO-PN group showed steatosis, but these changes were attenuated in the 8% and 33% FO-PN groups. CONCLUSION: The 30-40% ratio of FO to soybean oil with 20% of total calories supplied by lipid seems to be the best PN for preservation of hepatic MNC number and function.