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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.Key words: isolated rabbit heart, perfusion method, inotropic effect of dopamine, chronotropic effect of dopamine, arrhythmogenic effect of dopamine.In regard to the methods for perfusing isolated mammalian heart preparations, Langendorff's is well known and has been used for more than 100 years for cardiovascular research in physiological, biochemical and/or pharmacological aspects [1,2]. In a heart perfused with this method, the retrograde perfusion via the cannulated aorta is designed to produce a constant flow or constant pressure in the aorta with no outflow or only mere outflow from the right or left ventricle, and there is no venous return except for a quite small amount of perfusate drainage via the coronary sinus to the right or left atrium. In this respect, Langendorff's preparation is not working.Kodama in 1961 attempted to convert the isolated rabbit heart preparation into a working mode by constructing an artificial venous and arterial circulation system using silicon and glass tubes and perfusing the heart via the vena cava and pulmonary vein to keep sufficient venous return to the ventricles [3][4][5][6]. In a heart thus perfused with a venous and arterial circulation system that is similar to that in vivo, the simultaneous recordings of perfusate pressures at the various parts of veins and arteries were possible, and it was recognized that the pressure of either the right or left ventricle exceeds that of the pulmonary or ao...

1 The effects of the electrogenic Na-pump on spontaneous contraction in the isolated, longitudinal muscle of the duodenum of rats which had been on a potassium-deficient diet for 7 weeks, have been investigated. Intracellular levels of Na+ are increased by this diet. 2 The spontaneous contraction of the duodenal muscle was stopped, transiently, by 0.5 to 120 mM-KC Krebs solution. The period of decrease of tone and amplitude occurring immediately after adding KC was shortened when the external K+ concentration ([K]b) was increased from 0.5 to 120 mM.3 The decrease in tone and amplitude induced by KC was abolished by exposure ofthe tissue to 0 mM [K]b, by exposure to a temperature below 14C, and in the presence of ouabain (3 x 10-5_10-4 M).4 The spontaneous contraction of'Na-rich' duodenum in bathing medium containing 15mM K and following inhibition ofthe electrogenic Na-pump with cooling or ouabain was much the same as in the duodenum from rats fed balanced diets: i.e., increase of contractile tone immediately after adding KV.

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