Bottoms G D, Gimarc S, Pfeifer C
Department of Veterinary Physiology and Pharmacology, Purdue University, School of Veterinary Medicine, West Lafayette, Indiana 47907.
Circ Shock. 1991 Jan;33(1):1-6.
Endotoxin (LPS) was quantitated in canine plasma using the Limulus amebocyte lysate (LAL) chromogenic testing procedure. The assay was validated for sensitivity (25 pg/ml), recovery (90-110%), intra-assay precision (CV = 5.5), interassay precision (CV = 10), and stability of diluted, heat-treated, frozen samples (greater than or equal to 60 days). Canine plasma samples were analyzed for endotoxin following sublethal IV injections (cephalic and portal, bolus and slow infusion) of LPS. Pharmacokinetic analysis using the two-compartment open model on plasma LPS levels was possible for portal bolus, cephalic bolus, and portal slow infusion dogs. The results revealed that LPS given via cephalic bolus route had a lower clearance rate than LPS given via portal bolus route. Slow infusion of LPS into the portal vein revealed an increased distribution phase t1/2 in plasma and a slower elimination kel and beta rate than observed following a portal bolus injection of LPS. During a clinical endo(to)xemia, LPS enters the circulation slowly, and is therefore probably cleared more slowly; the prolonged low level of LPS may be responsible for many pathophysiological changes observed. Low levels of endotoxin were detected in plasma following hemorrhage, indicating that intestinal ischemia results in low levels of LPS leaking into the circulation.
使用鲎试剂显色检测法对犬血浆中的内毒素(脂多糖,LPS)进行定量分析。该检测方法在灵敏度(25 pg/ml)、回收率(90 - 110%)、批内精密度(CV = 5.5)、批间精密度(CV = 10)以及稀释、热处理、冷冻样品的稳定性(大于或等于60天)方面均经过验证。在对犬进行亚致死剂量的静脉注射(头静脉和门静脉,推注和缓慢输注)LPS后,分析犬血浆样本中的内毒素。对于门静脉推注、头静脉推注和门静脉缓慢输注的犬,使用二室开放模型对血浆LPS水平进行药代动力学分析是可行的。结果显示,通过头静脉推注途径给予的LPS清除率低于通过门静脉推注途径给予的LPS。将LPS缓慢输注到门静脉中,与门静脉推注LPS相比,血浆中的分布相t1/2增加,消除速率常数kel和β速率减慢。在临床内毒素血症期间,LPS缓慢进入循环,因此可能清除得更慢;LPS的长时间低水平可能是观察到的许多病理生理变化的原因。出血后血浆中检测到低水平的内毒素,表明肠道缺血导致低水平的LPS漏入循环。