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Bolus infusion of lipid emulsion can reverse cardiac pharmacotoxicity caused by local anesthetics and other lipophilic drugs. The mechanisms of this effect are not completely elucidated. The authors test the hypothesis that lipid emulsion infusion exerts direct, positive inotropic effects.Prospective, randomized animal study.University research laboratory.Adult male Sprague-Dawley rats.Rats anesthetized with isoflurane were given intravenous infusions (9 mL/kg over 1 min) of either 20% soybean oil-based emulsion or saline.Arterial pressure and aortic flow were measured continuously in intact animals. Lipid infusion increased aortic flow and arterial pressure faster and to a greater degree than did the same volume of saline infusion. Isolated rat hearts were studied using an isovolumetric, constant flow, nonrecirculating system. Left ventricular pressure was monitored. The infusion of lipid emulsion in the isolated heart dose-dependently increased rate pressure product, dP/dt, –dP/dt, and myocardial oxygen demand.Lipid emulsion exerts rapid, positive inotropic and positive lusitropic effects in both intact animal and isolated heart models. We hypothesize that this inotropy and the resulting increase in tissue blood flow contribute to the phenomenon of lipid reversal of cardiac toxicity caused by drug overdose.