Pentastarch in a Balanced Solution Reduces Hepatic Leukocyte Recruitment in Early Sepsis
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OBJECTIVE: To characterize the hepatic leukocyte endothelial cell interactions occurring in early sepsis and to determine whether this is influenced by fluid treatment. METHODS: Sepsis was induced by cecal ligation and perforation in C57Bl/6 mice. One of 6 iv fluid regimes was given immediately postsurgery and at 6 h. The hepatic microcirculation was examined by intravital microscopy at 6 h. RESULTS: All 0.9% saline-based solutions were associated with an increase in leukocyte-endothelial cell interactions as demonstrated by an increase in the rolling flux in the sham and naïve mice. In the septic mice treated with normal saline, there was a 20-fold increase in leukocyte adhesion within the postsinusoidal venules, compared to sham mice. Treatment with lactated Ringer's reduced the sepsis-mediated leukocyte recruitment by 50%. When septic mice received 6% pentastarch in a balanced solution or 3% saline, venular leukocyte adhesion was reduced by an additional 50%. When the pentastarch was prepared in normal saline there was no further reduction in venular leukocyte adhesion compared to the lactated Ringer's-treated mice. All hyperosmolar solutions improved the sepsis-induced reduction in sinusoidal perfusion but only the pentastarch in the balance solution significantly reduced the number of adherent leukocytes within the sinusoids. CONCLUSIONS: Hepatic leukocyte recruitment occurs early in sepsis. Pentastarch in a balanced solution but not in normal saline significantly reduces hepatic leukocyte recruitment, suggesting solution composition, as well as osmolarity impact the innate immune response.
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