The effects of etomidate on the contractility of failing and nonfailing human heart muscle.
We measured the effects of etomidate on contractility of human cardiac muscle. Muscles were obtained from the left ventricle and right atrium of 12 patients undergoing cardiac transplantation, and from the right atrium of 12 patients undergoing coronary artery bypass surgery. Muscles were studied at 37 degrees C and 1.0 Hz. Variables of isometric contraction were recorded before and after etomidate (0.04-80 microM) or its solvent, propylene glycol. The ability of beta-adrenergic stimulation to cause an inotropic effect after etomidate was also assessed. Etomidate caused a dose-dependent decrease in developed tension, which was statistically significant only at concentrations exceeding clinical doses (> or =20 microM; P < 0. 05). Decreases in maximum rates of contraction and relaxation paralleled changes in developed tension. beta-Adrenergic stimulation reversed the etomidate-induced decreases in developed tension and rates of contraction and relaxation to baseline (P > 0.05 compared with baseline). Thus, in human myocardium, etomidate exerts a dose-dependent negative inotropic effect, which is reversible with beta-adrenergic stimulation. Concentrations required to produce these negative inotropic effects are, however, in excess of those reached during clinical use. Therefore, etomidate-induced negative inotropy is unlikely to be a problem clinically, even in patients with cardiac dysfunction.


CONCLUSIONS
Etomidate produced a similar dose-dependent negative inotropic effect in both failing and nonfailing human myocardium. This effect was present only at concentrations exceeding those attained clinically and was reversible with beta-adrenergic stimulation.
Sprung
J
J
Department of General Anesthesiology and the Center for Anesthesiology Research, The Cleveland Clinic Foundation, OH 44195, USA. sprungj@ccf.org
Ogletree-Hughes
M L
ML
Moravec
C S
CS
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000368:Aged; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D002303:Cardiac Output, Low / Q000503:physiopathology*; D001026:Coronary Artery Bypass; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000494:pharmacology*; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D018686:Anesthetics, Intravenous; D007545:Isoproterenol; D005045:Etomidate