The antiendotoxin effects of polymyxin B in a feline model of endotoxemia
Metadata[+] Show full item record
Introduction: Directed, effective therapies for feline sepsis are needed to reduce the high morbidity and mortality associated with this disease. Materials and Methods: We investigated the anti-endotoxin effects of PMB in a blinded, placebo controlled fashion, both ex vivo in a feline whole blood culture system and in vivo, using a low-dose endotoxin infusion in cats (2ug/kg/hr IV x 4 hours). Serial measures of systemic inflammation, and hemodynamic stability, were compared between groups. Results: Ex vivo, PMB significantly decreased LPS-induced TNF production from whole blood. In vivo, endotoxin infusion resulted in the development of fever, hypotension, leucopenia and increased TNF activity. Polymyxin B (1mg/kg over 30 minutes) treatment decreased peak plasma TNF activity (p<0.001) and increased white blood cell count (p=0.019), with no adverse effects. Conclusions: Polymyxin B administration resulted in decreased peak plasma TNF activity and increased white blood cell count in this feline model of endotoxemia, with no adverse effects. Given the apparent safety and anti-endotoxin effects of PMB in this endotoxemia model, a carefully designed, randomized, blinded, placebo controlled clinical trial evaluating the use of PMB in naturally occurring Gram negative feline sepsis should be considered.
Veterinary biomedical sciencesVeterinary biomedical sciences
2010 Freely available theses (MU)