Abstract
Objectives: Increased morbidity and mortality in critically ill obese patients may result from an exaggerated inflammatory response and/or a diminished effectiveness of routine therapeutic strategies used in the critical care setting. The objectives of this study were to compare the effectiveness of hypertonic saline (HTS) resuscitation in obese and lean mice with sepsis and to address potential mechanisms underlying HTS-mediated protection against the inflammatory and microvascular responses to sepsis.
Methods: Intravital videomicroscopy was used to monitor and quantify the adhesion of platelets and leukocytes in the brain microcirculation of WT (C57 Bl/6) and ob/ob (B6.V-Lepob/J) mice subjected to cecal ligation and puncture (CLP) and resuscitated with either normal saline or HTS. The dual radiolabeled monoclonal antibody method was used to measure P-selectin expression in the microcirculation, while the sepsis-induced behavioral deficit was quantified using a multicompartment chamber test.
Results: HTS attenuated the accumulation of adherent leukocytes and platelets and the behavioral deficit observed at 4 h after CLP in both WT and ob/ob mice. CLP-induced upregulation of P-selectin in the brain microcirculation was attenuated by HTS in ob/ob, but not in lean, mice.
Conclusion: HTS exerts significant anti-inflammatory and anti-thrombogenic actions in obese septic mice. These responses may be related to the inhibitory effect of HTS on sepsis-induced P-selectin expression.
This work was financially supported by the Malcolm Feist Cardiovascular research endowment fund.