Evaluation of the anti-endotoxin effects of polymyxin B in a feline model of endotoxemia.
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.
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 E Campus Drive, Columbia, MO 65211, USA.
Claire R
CR
Sharp
Amy E
AE
DeClue
Carol E
CE
Haak
Allison R
AR
Honaker
Carol R
CR
Reinero
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002371:Cat Diseases / Q000097:blood / Q000188:drug therapy*; D002415:Cats; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D011112:Polymyxin B / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B