Sharp Claire R, DeClue Amy E, Haak Carol E, Honaker Allison R, Reinero Carol R
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 E Campus Drive, Columbia, MO 65211, USA.
J Feline Med Surg. 2010 Apr;12(4):278-85. doi: 10.1016/j.jfms.2009.12.014. Epub 2010 Feb 13.
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.
需要有针对性的、有效的猫败血症治疗方法来降低与该疾病相关的高发病率和死亡率。我们以盲法、安慰剂对照的方式研究了多粘菌素B（PMB）的抗内毒素作用，在猫全血培养系统中进行了体外研究，并在体内对猫进行低剂量内毒素输注。比较了各组之间全身炎症和血流动力学稳定性的系列测量结果。在体外，PMB显著降低了脂多糖诱导的全血肿瘤坏死因子（TNF）产生。PMB（30分钟内1mg/kg）在体内表现出抗内毒素作用，包括降低血浆TNF活性峰值（P<0.001）和增加白细胞计数（P=0.019），且无不良反应。鉴于PMB在该内毒素血症模型中具有明显的安全性和抗内毒素作用，应考虑进行一项精心设计的、随机、盲法、安慰剂对照的临床试验，以评估PMB在自然发生的革兰氏阴性猫败血症中的应用。
