Cave Grant, Harvey Martyn G, Castle Craig D
Monash Medical Centre, Victoria, Australia.
J Med Toxicol. 2006 Mar;2(1):4-7. doi: 10.1007/BF03161005.
In animal models, lipid emulsion therapy has been shown to ameliorate toxicity from a number of lipid soluble agents. This preliminary study addresses the hypothesis that pretreatment with lipid emulsion protects against propranolol toxicity in rodents.
Ten spontaneously ventilating Rattus norvegicus rats were pretreated with either lipid emulsion or 0.9% normal saline before undergoing a constant infusion of propranolol until death. An electrocardiogram (ECG) sampling of heart rate and a QRS duration was performed at two-minute intervals until demise.
There was no significant difference in lethal doses of propranolol between groups. Comparison of percent change in QRS prolongation and heart rate reduction was performed at 60% of the mean lethal dose in control animals. The percent change in QRS duration was reduced (from -0.9 to 17.3, p=0.016) in the intralipid pretreatment group. Attenuation of propranolol-induced bradycardia observed in the lipid emulsion group approached statistical significance (0% vs. 10.3%, p=0.06).
The results suggest that lipid emulsion may be effective in ameliorating propranolol toxicity in rats. Previous work gives reason to postulate a pharmacokinetic mechanism for this effect. The results represent encouraging exploratory work, and further work is planned to evaluate the role of lipid emulsion therapy in propranolol toxicity.
在动物模型中，脂质乳剂疗法已被证明可改善多种脂溶性药物的毒性。这项初步研究探讨了脂质乳剂预处理可预防啮齿动物普萘洛尔毒性的假说。
十只自主呼吸的挪威大鼠在持续输注普萘洛尔直至死亡前，分别用脂质乳剂或0.9%生理盐水进行预处理。每隔两分钟进行一次心电图（ECG）采样，记录心率和QRS波时限，直至动物死亡。
两组之间普萘洛尔的致死剂量无显著差异。在对照动物平均致死剂量的60%时，对QRS波延长百分比变化和心率降低进行比较。脂质乳剂预处理组QRS波时限的百分比变化有所降低（从-0.9降至17.3，p=0.016）。脂质乳剂组中观察到的普萘洛尔诱导的心动过缓的减轻接近统计学意义（0%对10.3%，p=0.06）。
结果表明脂质乳剂可能有效改善大鼠普萘洛尔毒性。先前的研究为这种效应的药代动力学机制提供了假设依据。这些结果代表了令人鼓舞的探索性工作，计划进一步开展工作以评估脂质乳剂疗法在普萘洛尔毒性中的作用。
