OBJECTIVE: Acute lung injury following peritonitis constitutes an enigmatic clinical problem with no specific therapy. Recently, immunomodulators such as azole compounds have been shown to attenuate shock-related tissue injury. The present investigation was undertaken to study the effect of fluconazole on acute lung injury and survival following faecal peritonitis in rats. SUBJECTS: Male Wistar rats weighing 225-235 g. DESIGN AND SETTING: Faecal peritonitis (Fp) was produced in four groups of adult male Wistar rats by intraperitoneal administration of non-sterile faecal suspension (1:1 w/v saline). A fifth group of rats was given sterile faecal material (SFM), which served as control. INTERVENTIONS: Rats in Fp groups were given fluconazole in doses of 0 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg by gavage 30 min before induction of peritonitis. The control animals received an equal volume of distilled water. MEASUREMENTS AND RESULTS: Survival over a period of 72 h, oxidative stress, neutrophil activity, and lung injury were measured. This study showed a 90% survival in the fluconazole-treated group compared to only 20% survival in untreated rats (P<0.008 log-rank test). The lungs of animals with Fp showed massive pathological changes including intraalveolar oedema, fibrosis, and mixed inflammatory cell infiltrate. These changes were dose-dependently attenuated by fluconazole. Enhanced oxidative stress (P<0.001) and neutrophil activity in the peritoneal fluid and lung (P<0.001) in Fp animals was dose-dependently reduced by fluconazole. CONCLUSION: This study clearly suggests the role of neutrophils in Fp-induced tissue injury/mortality, which may be dose-dependently, attenuated by fluconazole.
OBJECTIVE: Acute lung injury following peritonitis constitutes an enigmatic clinical problem with no specific therapy. Recently, immunomodulators such as azole compounds have been shown to attenuate shock-related tissue injury. The present investigation was undertaken to study the effect of fluconazole on acute lung injury and survival following faecal peritonitis in rats. SUBJECTS: Male Wistar rats weighing 225-235 g. DESIGN AND SETTING: Faecal peritonitis (Fp) was produced in four groups of adult male Wistar rats by intraperitoneal administration of non-sterile faecal suspension (1:1 w/v saline). A fifth group of rats was given sterile faecal material (SFM), which served as control. INTERVENTIONS:Rats in Fp groups were given fluconazole in doses of 0 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg by gavage 30 min before induction of peritonitis. The control animals received an equal volume of distilled water. MEASUREMENTS AND RESULTS: Survival over a period of 72 h, oxidative stress, neutrophil activity, and lung injury were measured. This study showed a 90% survival in the fluconazole-treated group compared to only 20% survival in untreated rats (P<0.008 log-rank test). The lungs of animals with Fp showed massive pathological changes including intraalveolar oedema, fibrosis, and mixed inflammatory cell infiltrate. These changes were dose-dependently attenuated by fluconazole. Enhanced oxidative stress (P<0.001) and neutrophil activity in the peritoneal fluid and lung (P<0.001) in Fp animals was dose-dependently reduced by fluconazole. CONCLUSION: This study clearly suggests the role of neutrophils in Fp-induced tissue injury/mortality, which may be dose-dependently, attenuated by fluconazole.
Authors: Edward Abraham; Peter Andrews; Massimo Antonelli; Laurent Brochard; Christian Brun-Buisson; Geoffrey Dobb; Jean-Yves Fagon; Johan Groeneveld; Jordi Mancebo; Philipp Metnitz; Stefano Nava; Michael Pinsky; Peter Radermacher; Marco Ranieri; Christian Richard; Robert Tasker; Benoit Vallet Journal: Intensive Care Med Date: 2004-06-26 Impact factor: 17.440