DIFFERENTIAL-EFFECTS OF ETOMIDATE, PROPOFOL, AND MIDAZOLAM ON CALCIUMAND POTASSIUM CHANNEL CURRENTS IN CANINE MYOCARDIAL-CELLS

Background: Intravenous anesthetics etomidate, propofol, and midazolam produce negative inotropic effects of various degrees. The mechanism underlying these differences is largely unknown. Methods: The effects of intravenous anesthetics on L-type Ca2+, transient outward and inwar d-rectifier K+ channel currents (I-Ca, I-Kto, and IK1) were compared i n canine ventricular cells using the whole-cell voltage-clamp techniqu e. I-Ca and I-K were elicited by progressively depolarizing cells from -40 to +40 mV, and from -90 to +60 mV, respectively. The peak amplitu de and time-dependent inactivation rate of I-Ca and I-K were measured before, during, and after the administration of equimolar concentratio ns (5, 30, or 60 mu M) of etomidate, propofol, or midazolam. Results: Exposure to etomidate, propofol, and midazolnm produced a concentratio n-dependent inhibition of I-Ca. Midazolam was the most potent intraveu ous anesthetic; at 60 mu M, etomidate, propofol, and midazolam decreas ed peak I-Ca by 16 +/- 4% (mean +/- SEM), 33 +/- 5%, and 47 +/- 5%, re spectively. Etomidate, propofol, and midazolam given in a 60-mu M conc entration decreased IKto by 8 +/- 3%, 9 +/- 2%, and 23 +/- 3%, respect ively. IK1 was decreased by 60 mu M etomidate and midazolam by 20 +/- 6% and 14% +/- 5%, respectively. Propofol had no effect on IK1. Conclu sions: At equimolar concentrations, intravenous anesthetics decreased the peak I-Ca, I-Kto, and I-K1, with various degrees of potency. Effec ts of anesthetics on I-Ca were significantly greater compared with the ir effects on K+ currents. These findings suggest that the negative in otropic actions of etomidate, propofol, and midazolam are related, at least in part, to decreased I-Ca. Some effects, such as I-K inhibition , may partially antagonize effects of decreased I-Ca. Indeed, the fina l effect of these intravenous anesthetics on myocardium will be the su m of these and other sarcalemmal and intracellular effects.