Evaluation of the anti-endotoxin effects of polymyxin B in a feline model of endotoxemia.
Author(s): Sharp CR, DeClue AE, Haak CE, Honaker AR, Reinero CR
Affiliation(s): Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 E Campus Drive, Columbia, MO 65211, USA.
Publication date & source: 2010-04, J Feline Med Surg., 12(4):278-85. Epub 2010 Feb 13.
Publication type: Research Support, Non-U.S. Gov't
Directed, effective therapies for feline sepsis are needed to reduce the high morbidity and mortality associated with this disease. We investigated the anti-endotoxin effects of polymyxin B (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. Serial measures of systemic inflammation, and hemodynamic stability, were compared between groups. Ex vivo, PMB significantly decreased lipopolysaccharide-induced tumor necrosis factor (TNF) production from whole blood. PMB (1mg/kg over 30min) demonstrated anti-endotoxin effects in vivo, including decreased peak plasma TNF activity (P<0.001) and increased white blood cell count (P=0.019), 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. Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.