Negative inotropic effect of etomidate in rabbit papillary muscle

The effect of etomidate on the developed force of isometrically contracting rabbit papillary muscles in modified Krebs-Henseleit bicarbonate medium was evaluated under various stimulation conditions to gain insight into the mechanism underlying the negative inotropic effect of this anesthetic. Myocardial depressant effects of etomidate (2 and 4 mg/L) on steady-state contractions at low stimulation frequencies (0.1-0.5 Hz) were more pronounced than the effects on either steady-state contraction at high stimulation frequencies (1.0-2.0 Hz) or the effects on post-rest potentiated state contractions. Increases in the concentration of extracellular Ca2+ from an initial level of 2.5 mM to 3.4-4.0 mM reversed the effect of 2 mg/L of etomidate, whereas an increase to 4.6-5.0 mM was required to reverse the effect of 4 mg/L of etomidate. The dependence of post-rest potentiation on the duration of the preceding rest period was virtually unaffected by etomidate. These results suggest that etomidate inhibits the influx of extracellular Ca2+ but has little effect on the availability of intracellular Ca2+ required for the activation of myocardial contractile activity. Because the concentrations of etomidate required to produce negative inotropic responses in the present study are substantially greater than those likely to be achieved under clinical conditions, the present results also suggest that negative inotropism is unlikely in patients with normal hearts.