The action of 2,3‐butanedionemonoxime on the inotropic state in guinea‐pig myocardium

Publisher Website
Google Scholar
Abstract
Isolated papillary muscles from guinea‐pig right ventricles were used (temperature 33 °C, stimulation frequency 0.5 Hz). Isometric twitch and action potentials were recorded. Upon addition of 2, 3‐butanedionemonoxime (BDM) (2 mm) the peak twitch force was reduced from 4.17 ± 0.4 mN/mm2to 1.68 ± 0.3 mN/mm2(n =9,P< 0.001). The time course of the isometric twitch was slightly altered. Time to peak tension (TPT) was reduced by 12.0 ± 3% (n =9,P< 0.001) whereas time to half relaxation (THR) was left unaffected. The rate of rise offorce was reduced by 35 ± 3.2 mN/mm2s i.e. 46 ± 3 %. The action potential duration and amplitude was not significantly changed by the drug. The shape of the curve relating peak twitch force of an extra beat to the preceding test interval, i.e. mechanical restitution, was affected by 2 mM 2,3‐butanedionemonoxime. The curve reached its maximum faster after addition of the drug. Maximum postextrasystolic potentiation (force in response to the prepreceding test interval) was 3.2 ± 0.4 mN/mm2in 2 mm 2,3‐butanedionemonoxime and 7.6 ± 0.7 mN/mm2in control (n= 6). However the percentage potentiation was very similar in control (82%) and in presence of 2,3‐butanedionemonoxime (91%). Peak twitch force in relation to peak force of the preceding potentiated contraction during decay of postextrasystolic potentiation was analysed. There was a linear relation between the variables, the slope being 0.34 ± 0.04 in control and 0.30 ± 0.02 in 2J‐butane dionemonoxime. This suggests that the drug is without an action on the fraction of calcium recirculating within the cell. As previously suggested the negative inotropic action of BDM can be explained by an action on cross‐bridge kinetics, however the effects on the mechanical restitution curve suggests an additional action on the calcium handling by the sarcoplasmic reticulum.