IN-VITRO EFFECTS OF ELTANOLONE ON RAT MYOCARDIUM

Background: Eltanolone is a new short-acting intravenous induction age nt. However, its effects on intrinsic myocardial contractility remain unknown. Methods: The effects of eltanolone and its solvent (soya bean emulsion) on the intrinsic contractility of rat left ventricular papi llary muscles were investigated in vitro (Krebs-Henselelt solution, 29 degrees C, pH 7.40, Ca2+ 0.5 mM, stimulation frequency 12 pulses/min) . We studied contraction; relaxation; contraction-relaxation coupling under high and low loads; and postrest potentiation. Results: Eltanolo ne (0.1, 0.3, 1, 3, and 10 mu g . ml(-1)) induced no significant inotr opic effect, as shown by the lack of changes in maximum unloaded short ening velocity and active isometric force. Eltanolone did not signific antly modify the contraction-relaxation coupling under low load, sugge sting that it did not modify calcium uptake by the sarcoplasmic reticu lum, Eltanolone did not significantly modify the contraction-relaxatio n coupling under high load, suggesting that it did not modify calcium myofilament sensitivity. Eltanolone decreased the postrest potentiatio n in a concentration-dependent manner (from 150 +/- 14% to 118 +/- 9% at 10 mu g . ml(-1), P<0.001), suggesting a decrease in the maximum ca pacity of calcium release by the sarcoplasmic reticulum, whereas its s olvent did not. However, eltanolone did not slow postrest potentiation recovery, as shown by the absence of significant changes in the recov ery slope, tau (4.5 +/- 1.4 vs. 3.8 +/- 1.0 beats; difference not stat istically significant). Conclusions: Eltanolone induced no significant inotropic effect on rat myocardium. It induced a decrease in the calc ium release function of the sarcoplasmic reticulum, but this effect wa s not sufficiently important to modify the inotropic properties.