Inotropic, chronotropic, and arrhythmogenic effects of dopamine on the isolated working heart of rabbit

Abstract

Some improvements of Kodama's method for perfusing the isolated rabbit heart in its working mode were made. Increases in the right and left atrium pressure, together with an increase in the pulmonary artery pressure, were observed to occur immediately after the start of venous return, and then all of the increased pressures were found to remain at each constant level. In these stable states, the administration of dopamine (DA) into the perfusate was found to produce dose-related increases in contractile activities. In the preparations denervated with reserpine or 6-hydroxydopamine, in which tyramine (Ty) produced no response, the inotropic effectiveness of DA did not differ from that in the normal ones. On the other hand, responses to noradrenaline (NA) were found to increase significantly after the denervation. DA produced a dose-related increase in heart rates in the normal preparation, and this effect was greatly suppressed in the denervated preparations, suggesting that the primary chronotropic effect of DA is an indirect one via the release of NA from the sympathetic nerve terminals. Arrhythmogenic effects of NA, Ty or DA were also observed in these preparations. At all the doses tested, the incidence rates by NA were as high as 50% or more, the type of arrhythmia being recognized as atrial or ventricular extrasystole from the ECG analysis. On the other hand, the rates by DA were relatively low, less than 34%. From a comparison of the incidence rates between the normal and denervated preparations, this effect of DA was considered to be primarily an indirect one.