INTRODUCTION: 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. METHODS: 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. RESULTS: 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). INTERPRETATION: 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.
INTRODUCTION: 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 propranololtoxicity in rodents. METHODS: Ten spontaneously ventilating Rattus norvegicusrats 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. RESULTS: 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). INTERPRETATION: The results suggest that lipid emulsion may be effective in ameliorating propranololtoxicity 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 propranololtoxicity.
Authors: Kimberly F Macala; Rachel G Khadaroo; Sareh Panahi; Ferrante S Gragasin; Stephane L Bourque Journal: PLoS One Date: 2018-08-30 Impact factor: 3.240