Detoxification effects of long-chain versus a mixture of medium- and long-chain triglyceride-based fat emulsion on propafenone poisoning

In the present study, we aimed to compare the detoxifying effects of two fat emulsions containing either long-chain triglyceride or a mixture of medium-chain and long-chain triglycerides in the propafenone-poisoned rat model. Rats were randomly divided into 3 groups according to the fat emulsions used: long-chain triglyceride-based fat emulsion (LL) group; medium-chain and long-chain triglyceride-based fat emulsion (ML) group; normal saline (NS) group. Propafenone was continuously pumped (velocity=70 mg/kg per h) until the mean blood pressure dropped to 50% of basal level. Then, LL/ML fat emulsions or NS was intravenously infused instantly with a loading-dose (1.5 mL/kg) and a maintenance dose (0.25 mL/kg per min) for 1 h. Subsequently, the propafenone was added to plasma (3.5 μg/mL) in vitro, mixed with three doses of LL or ML (1, 2, or 4%). Finally, after centrifugation, the concentration of propafenone was measured. Rats treated with LL exhibited accelerated recovery, characterized by higher blood pressure and heart rate. Rats in both the LL and ML groups demonstrated decreased propafenone in plasma (time-points: 15, 25, and 60 min). However, rats that received LL showed lower propafenone in myocardial tissue at the end of detoxification treatment. Rats in the ML group had the lowest value of pH, the minimum content of HCO3-, and the highest production of lactic acid at the end. In the in vitro experiments, propafenone decreased more dramatically in the LL group compared to the ML group. Long-chain triglyceride fat emulsion had a better effect on treating propafenone poisoning in rats.

本研究旨在以普罗帕酮中毒大鼠模型为研究对象，对比两种脂肪乳剂的解毒效果：一种含长链甘油三酯，另一种含中链与长链甘油三酯的混合物。实验大鼠根据所使用的脂肪乳剂类型被随机分为3组：长链甘油三酯型脂肪乳剂（long-chain triglyceride-based fat emulsion，LL）组、中长链甘油三酯混合型脂肪乳剂（medium-chain and long-chain triglyceride-based fat emulsion，ML）组，以及生理盐水（normal saline，NS）组。以70 mg/(kg·h)的速率持续泵注普罗帕酮，直至大鼠平均血压降至基础水平的50%。随后即刻经静脉输注LL/ML型脂肪乳剂或生理盐水：先给予负荷剂量1.5 mL/kg，再以0.25 mL/(kg·min)的速率维持输注1小时。后续开展体外实验：将普罗帕酮以3.5 μg/mL的浓度加入血浆样本，分别与1%、2%、4%三种剂量的LL或ML型脂肪乳剂混合，离心后检测血浆中普罗帕酮的浓度。接受LL组干预的大鼠恢复速度更快，表现为血压与心率水平更高。在15、25、60分钟三个时间点，LL组与ML组大鼠的血浆普罗帕酮浓度均有所降低。但在解毒治疗结束时，LL组大鼠心肌组织中的普罗帕酮浓度更低。治疗结束时，ML组大鼠的血液pH值最低、碳酸氢根（HCO3-）含量最少，且乳酸生成量最高。体外实验中，LL组的血浆普罗帕酮浓度下降幅度较ML组更为显著。综上，长链甘油三酯型脂肪乳剂对大鼠普罗帕酮中毒的治疗效果更优。