OBJECTIVE: To compare the hemodynamic side effects of three structurally different lipid emulsions. DESIGN: Randomized, controlled, prospective animal study. SETTING: University research laboratory. SUBJECTS: Six chronically instrumented mongrel dogs. INTERVENTIONS: On separate days, all animals were submitted to three different treatments, in a randomized order. After baseline measurements, either a long-chain triglyceride emulsion (treatment 1), a mixed medium-chain triglyceride/long-chain triglyceride emulsion (treatment 2), or an omega3 polyunsaturated fatty acid long-chain triglyceride (PUFA) emulsion (treatment 3) was administered intravenously over 30 mins. MEASUREMENTS AND MAIN RESULTS: Global and regional hemodynamics (sonomicrometry) were recorded for 2 hrs after baseline measurements. Arterial blood gases and plasma concentrations of hemoglobin, triglycerides, total protein, and glucose were recorded for 2 hrs. Long-chain triglycerides did not affect the cardiovascular performance in awake animals. However, medium-chain triglycerides/long-chain triglycerides and omega3 PUFA caused marked increases in systemic vascular resistance (from 1833 +/- 154 to 3277 +/- 163 mm Hg/dynexsec5, p < .05), heart rate (from 89 +/- 6 to 158 +/- 10 beats/min, p < .05), and depressed ventricular performance (wall-thickening fraction [as percentage from baseline] decreased to 53 +/- 9%, p < .05). CONCLUSIONS: Commercially available lipid emulsions can cause profound cardiovascular side effects at high doses, depending on their composition. Whereas long-chain triglyceride emulsions have virtually no effects on hemodynamics in normal dogs, medium-chain triglyceride/long-chain triglyceride, and omega3 PUFA emulsions should be used with caution in critically ill patients with compromised cardiovascular function.