INTERPRETATION OF THE INOTROPIC EFFECT OF 2,3-BUTANEDIONE MONOXIME ONTHE ISOMETRIC TWITCH OF GUINEA-PIG PAPILLARY-MUSCLE

The negative inotropic effect of 2,3-butanedione monoxime (BDM) on the isometric twitch of guinea-pig papillary muscle was analysed by param eters characterizing the time course of the mechanogram. BDM at concen trations of up to 4 mmol/l produced a clear negative inotropic effect, whereas the Ca transient measured in isolated cardiomyocytes was only slightly affected. Peak force was more reduced than dF/dt(max) and dF /dt(min). This led to an earlier, more narrow peak and a shortening of twitch duration. Based on a reaction scheme for the cross-bridge cycl e, a mathematical model using a Ca transient and mechanograms as input data has been developed. The kinetic parameters were estimated by fit ting the model to various time courses of force obtained at rising con centrations of BDM. BDM decreased the ratio of rate constants for cros s-bridge attachment and detachment in a concentration-dependent manner : the formation of crossbridges became inhibited, whereas dissociation was promoted. Above 4 mmol/l BDM the more marked alterations of the p arameters of the mechanogram indicated an additional suppressing effec t on intracellular Ca supply. The computer analysis suggests how the c ellular mechanism(s) of the BDM-induced negative inotropic effect are reflected in the time course of the mechanogram