Poulin Braim Amy E, MacDonald Melinda H, Bruss Michael L, Grattendick Ken J, Giri Shri N, Margolin Solomon B
Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Am J Vet Res. 2009 Aug;70(8):1031-42. doi: 10.2460/ajvr.70.8.1031.
To characterize effects of IV administration of pirfenidone on clinical, biochemical, and hematologic variables and circulating tumor necrosis factor (TNF)-alpha concentrations in horses after infusion of a low dose of endotoxin.
18 healthy adult horses.
Horses were randomly assigned to 3 groups (n = 6 horses/group) and administered an IV infusion of 30 ng of endotoxin/kg or saline (0.9% NaCl) solution during a 30-minute period. Lipopolysaccharide-pirfenidone horses received endotoxin followed by pirfenidone (loading dose of 11.6 mg/kg and then constant rate infusion [CRI] at 9.9 mg/kg/h for 3 hours). Lipopolysaccharide-saline horses received endotoxin followed by infusion (loading dose and CRI for 3 hours) of saline solution. Saline-pirfenidone horses received saline solution followed by pirfenidone (loading dose and then CRI for 3 hours). Physical examination variables were recorded and blood samples collected at predetermined intervals throughout the 24-hour study period. Blood samples were used for CBCs, biochemical analyses, and determinations of TNF-alpha concentrations.
IV infusion of pirfenidone after administration of a low dose of endotoxin failed to attenuate the clinical, clinicopathologic, or cytokine alterations that developed secondary to endotoxin exposure. Intravenous infusion of pirfenidone after administration of saline solution induced mild transient clinical signs, but associated clinicopathologic changes were not detected.
IV administration of pirfenidone was tolerated with only mild transient clinical adverse effects during infusion. However, administration of pirfenidone did not protect horses from the systemic effects of experimentally induced endotoxemia. Further studies of related, but more potent, drugs may be warranted.
描述静脉注射吡非尼酮对低剂量内毒素输注后马匹的临床、生化和血液学指标以及循环肿瘤坏死因子（TNF）-α浓度的影响。
18匹健康成年马。
将马随机分为3组（每组6匹马），在30分钟内静脉输注30 ng内毒素/kg或生理盐水（0.9%氯化钠）溶液。脂多糖-吡非尼酮组马匹先接受内毒素，随后接受吡非尼酮（负荷剂量为11.6 mg/kg，然后以9.9 mg/kg/h的恒定速率输注[CRI]3小时）。脂多糖-生理盐水组马匹先接受内毒素，随后输注（负荷剂量和CRI 3小时）生理盐水溶液。生理盐水-吡非尼酮组马匹先接受生理盐水溶液，随后接受吡非尼酮（负荷剂量，然后CRI 3小时）。在整个24小时研究期间，按预定间隔记录体格检查指标并采集血样。血样用于全血细胞计数、生化分析以及TNF-α浓度测定。
低剂量内毒素给药后静脉注射吡非尼酮未能减轻内毒素暴露继发的临床、临床病理或细胞因子改变。生理盐水溶液给药后静脉输注吡非尼酮引起轻度短暂的临床症状，但未检测到相关的临床病理变化。
静脉注射吡非尼酮在输注期间仅产生轻度短暂的临床不良反应，可耐受。然而，吡非尼酮给药并不能保护马匹免受实验性诱导的内毒素血症的全身影响。可能需要对相关但更有效的药物进行进一步研究。
