Abstract
Volatile anesthetics are known to have immunomodulatory effects in conditions of organ injury. A recent study in an experimental sepsis model has shown remarkably improved survival when mice were exposed to volatile anesthetics. In the present study, we show that hexafluoroisopropanol – a water-soluble primary sevoflurane metabolite – has beneficial effects on the overall survival in a murine model of cecal ligation and puncture. Seven-day survival as well as tissue damage markers including transaminases and high mobility group box protein-1 were assessed as measures of end organ damage. In animals undergoing cecal ligation and puncture procedure hexafluoroisopropanol conditioning - but not late postconditioning 24 hours after sepsis induction - significantly increased survival rate (17% vs. 77%, p = 0.037) and attenuated secretion of organ damage markers. This study shows survival benefits by administration of the metabolite of a volatile anesthetic. If successfully translated, hexafluoroisopropanol might offer interesting therapeutic opportunities in the future treatment of abdominal sepsis.
Highlights
Volatile anesthetics have been shown to positively affect outcome after ischemia reperfusion injuries in both clinical and basic research studies [1,2,3]
We investigated in a state-of-the-art model of murine sepsis with intra-abdominal focus whether HFIP application improves overall survival of septic animals
In a murine Cecal ligation and puncture (CLP) sepsis model we found that intravenous administration of water-soluble HFIP showed markedly improved overall 7-day survival (77%) compared to the CLP group (17%) when administered in saline at a dose of 0.015 mg/g immediately after CLP surgery (p = 0.037, N = 12) (Figure 1)
Summary
Volatile anesthetics have been shown to positively affect outcome after ischemia reperfusion injuries in both clinical and basic research studies [1,2,3]. Most recently, it has been demonstrated in an experimental sepsis model that conditioning with desflurane or sevoflurane and post-conditioning with sevoflurane improves survival in murine septic peritonitis [4]. Trifluorinated small molecules have previously been shown to exert immunomodulatory effects similar to volatile anesthetics in an in vitro model of lipopolysaccharide (LPS)induced cell injury [5]. Tissue damage markers including blood urea, transaminases and high mobility group box protein-1 (HMGB-1) were determined as measures for end organ damage
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