Moore J N, Norton N, Barton M H, Hurley D J, Reber A J, Donovan D C, Vandenplas M L, Parker T S, Levine D M
College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA.
Equine Vet J. 2007 May;39(3):243-8. doi: 10.2746/042516407x173343.
Endotoxaemia currently is associated with a poor prognosis in horses. The results of recent trials in other species indicate that phospholipid emulsions reduce the deleterious effects of endotoxin (LPS). However, in a previous study in horses, a 2 h infusion of emulsion caused an unacceptable degree of haemolysis.
Rapid administration of a lower total dose of emulsion would reduce the effects of LPS and induce less haemolysis; the emulsion would reduce inflammatory effects of LPS in vitro.
Twelve healthy horses received an i.v. infusion either of saline or a phospholipid emulsion (100 mg/kg), followed immediately by E. coli 055:B5 LPS (30 ng/kg). Clinical parameters, haematological profiles, serum tumour necrosis factor (TNF) activity, serum lipid profiles, urine analyses and severity of haemolysis were monitored before and at selected times after LPS. Monocytes were also incubated in vitro with LPS in the presence or absence of emulsion, after which TNF and tissue factor activities were determined.
Clinical signs of endotoxaemia were reduced in horses receiving the emulsion, including clinical score, heart rate, rectal temperature, serum TNF activity, and the characteristic leucopenic response to LPS, when compared to horses not receiving the emulsion. Three horses receiving the emulsion had none, 2 had mild and one had moderate haemolysis. There were no differences in urinalysis results and creatinine concentrations, either within the groups over time or between the groups. Serum concentrations of phosphatidylcholine, bile acids and triglycerides peaked immediately after the infusion; there were no significant changes in concentrations of nonesterified fatty acids or cholesterol. Incubation of equine monocytes with emulsion prevented LPS-induced TNF and tissue factor activities.
Rapid administration of emulsion significantly reduced inflammatory effects of LPS in vivo and caused a clinically insignificant degree of haemolysis. The results of the in vitro studies indicate that emulsion prevents not only LPS-induced synthesis of cytokines, but also expression of membrane-associated mediators (i.e. tissue factor).
Rapid i.v. administration of emulsions containing phospholipids that bind endotoxin may provide a clinically useful method of treating endotoxaemia in horses.
目前内毒素血症与马的预后不良相关。近期在其他物种中进行的试验结果表明，磷脂乳剂可减轻内毒素（LPS）的有害影响。然而，在之前一项针对马的研究中，输注2小时乳剂会导致不可接受程度的溶血。
快速给予较低总剂量的乳剂会减轻LPS的影响并引发较少的溶血；该乳剂会在体外减轻LPS的炎症作用。
12匹健康马静脉输注生理盐水或磷脂乳剂（100mg/kg），随后立即静脉注射大肠杆菌055:B5 LPS（30ng/kg）。在给予LPS之前及之后选定时间监测临床参数、血液学指标、血清肿瘤坏死因子（TNF）活性、血脂谱、尿液分析及溶血严重程度。单核细胞也在体外与LPS共同孵育，存在或不存在乳剂，之后测定TNF和组织因子活性。
与未接受乳剂的马相比，接受乳剂的马内毒素血症的临床体征减轻，包括临床评分、心率、直肠温度、血清TNF活性以及对LPS特征性的白细胞减少反应。3匹接受乳剂的马无溶血，2匹有轻度溶血，1匹有中度溶血。尿液分析结果和肌酐浓度在各时间组内及组间均无差异。输注后血清磷脂酰胆碱、胆汁酸和甘油三酯浓度立即达到峰值；非酯化脂肪酸或胆固醇浓度无显著变化。马单核细胞与乳剂共同孵育可防止LPS诱导的TNF和组织因子活性。
快速给予乳剂可显著减轻LPS在体内的炎症作用，并引发临床上无显著意义的溶血程度。体外研究结果表明，乳剂不仅可防止LPS诱导的细胞因子合成，还可防止膜相关介质（即组织因子）的表达。
快速静脉注射结合内毒素的含磷脂乳剂可能为治疗马内毒素血症提供一种临床上有用的方法。
