The role of fat emulsion therapy in a rodent model of propranolol toxicity: a preliminary study.
BACKGROUND
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).


CONCLUSIONS
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.
Cave
Grant
G
Monash Medical Centre, Victoria, Australia. grantcave@xtra.co.nz
Harvey
Martyn G
MG
Castle
Craig D
CD
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D011433:Propranolol / Q000506:poisoning; D051381:Rats; D013997:Time Factors
D005217:Fat Emulsions, Intravenous; D011433:Propranolol