Mechanism of the Negative Inotropic Effect of Propofol in Isolated Ferret Ventricular Myocardium

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Background:The aim of this study was to investigate propofol's effect on myocardial contractility and relaxation and examine its underlying mechanism of action in isolated ferret ventricular myocardium.Methods:The effects of propofol on variables of contractility and relaxation and on the free intracellular Ca++ transient detected with the Ca++ -regulated photoprotein aequorin were analyzed. Propofol's effects were evaluated in a preparation in which the sarcoplasmic reticulum function was impaired by ryanodine. The effects of propofol's solvent, intralipid, on myocardial contractility, relaxation, and the intracellular Ca++ transient also were examined.Results:Propofol, at concentrations of 10 μM or greater, decreased contractility and, at concentrations of 30 μM or greater, decreased the amplitude of the intracellular Ca++ transient. At equal peak force, control peak aequorin luminescence in [Ca++]o=2.25 mM and peak aequorin luminescence in 300 μM propofol in [Ca++]o>2.25 mM did not differ, which suggests that propofol does not alter myofibrillar Ca++ sensitivity. After inactivatlon of sarcoplasmic reticulum Ca++ release with 1 μM ryanodine, a condition in which myofibrillar activation depends almost exclusively on transsarcolemmal Ca++ influx, propofol caused a decrease in contractility and in the amplitude of the intracellular Ca++ transient. Under these conditions, propofol's relative negative inotropic effect did not differ from that in control muscles not exposed to ryanodine. Propofol's solvent, 10% intralipid, exerted a modest positive inotropic effect in this preparation. The intracellular Ca++ transient was unchanged by intralipid. Neither propofol nor intralipid altered the load sensitivity of relaxation.Conclusions:These findings suggest that the negative inotropic effect of propofol results from a decrease in intracellular Ca++ availability with no changes in myofibrillar Ca++ sensitivity. At least part of propofol's action is attributable to inhibition of transsarcolemmal Ca++ influx.

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