[The effects of midazolam on the mechanical and electrical properties of the isolated ventricular myocardium].

Abstract

The direct effects of midazolam on isometric force of contraction (Fc) and on transmembrane action potential (AP) in electrically driven right ventricular papillary muscles were investigated. The results were compared with the effects of thiopental. Midazolam (0.01-200 mumol/l) had a concentration-dependent maximal negative inotropic effect of 94 +/- 4% compared with the pre-drug value on the papillary muscles of animals pretreated with reserpine (RES) [7.5 mg/kg b.wt. i.p., 16-18 h prior to the study]. The IC25 and IC50 values were 2.9 mumol/l (2.0-4.5; n = 9) and 12.4 mumol/l (6.5-30; n = 9) respectively. However, on the papillary muscles of untreated animals (nRES) midazolam developed a concentration-dependent positive inotropic effect (maximal 20 +/- 7%). Midazolam at a clinically relevant concentration of 2.8 mumol/l (= 1 microgram/ml; equivalent with the maximum plasma level following a midazolam i.v. bolus injection of 0.15 mg/kg b. wt.) reduced Fc by 15 +/- 3% (p less than 0.05) compared with the pre-drug value on the RES papillary muscles (n = 6) and increased Fc by 3 +/- 0.3% (p less than 0.05) on nRES animals. The resting membrane potential (RMP), the AP amplitude (APA) and the AP duration at 20% (APD20) and 90% (APD90) repolarisation showed no significant differences with midazolam (2.8 mumol/l; n = 5). Thiopental (0.01-200 mumol/l) produced a concentration-dependent maximal negative inotropic effect of 86 +/- 2% compared with the pre-drug value on the papillary muscles of nRES animals.(ABSTRACT TRUNCATED AT 250 WORDS)