Studies on the positive inotropic effect of dopamine in the guinea-pig heart

Mugelli, Alessandro; Ledda, F.; Mantelli, Laura; Torrini, M.; Maccioni, Tiziana

doi:10.1007/bf00501263

Cited by 22 publications

(17 citation statements)

References 26 publications

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“…In regard to the changes in the inotropic effects of DA after denervation, several reports show a reduction of its effectiveness [8,9,15]. In the present study, however, the positive inotropic effects of DA on the denervated preparations were found to be as great as those observed in the normal ones (Fig.…”

Section: Dosecontrasting

confidence: 62%

“…A chemical denervation of the sympathetic nerve terminals was made by a pretreatment of the animals with reserpine [7][8][9][10][11][12] or 6-OHDA [13][14][15], the former being dissolved in 20% ascorbic acid solution and given intraperitoneally at doses of 2 to 8 mg/kg body weight 24 h before isolation of the heart, and the latter by an intravenous injection at the ear vein at doses of 50 to 100 mg/kg body weight 24 h before isolation or by repeated injections, once a day for 2 days, at a dose of 50 mg/kg body weight. In each isolated heart it was determined that the pretreatments produced complete chemical denervations of the sympathetic nerve terminals, when there was no change in the HR and contraction forces in response to tyramine (Ty) applied to the perfusate.…”

Section: Methodsmentioning

confidence: 99%

“…6B). The receptors producing the direct inotropic effects of DA in the heart were reported for rabbit [30,31] and man [32] to be β-and α-adrenoceptors, for guinea pig [9] and rat [33] to be β-adrenoceptor only, and for chick embryo [34] to be β-adrenoceptor and subtype DA2-receptors. DA has been shown to increase L-type Ca 2+ currents and to produce the inotropic effect that is mediated through the direct stimulation of β-adrenoceptor in the single atrial and ventricular myocytes of the rat [33].…”

Section: Dosementioning

confidence: 99%

“…To clarify whether these inotropic effects of DA as well as the chronotropic ones are direct actions on the cardiac muscles or indirect ones by releasing noradrenaline (NA) from the sympathetic nerve terminals in the cardiac muscles, the sympathetically denervated preparations by the treatments with reserpine [7][8][9][10][11][12] or 6-hydroxydopamine (6-OHDA) [13][14][15] were used, as reported previously. To the author's knowledge, it remains unknown whether the arrhythmogenic effects of DA could be produced by the direct or indirect actions.…”

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confidence: 99%

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Inotropic, Chronotropic, and Arrhythmogenic Effects of Dopamine on the Isolated Working Heart of Rabbit

Wakita¹

2007

J. Physiol. Sci

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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...

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Section: Dosecontrasting

confidence: 62%

Section: Methodsmentioning

confidence: 99%

Section: Dosementioning

confidence: 99%

mentioning

confidence: 99%

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Inotropic, Chronotropic, and Arrhythmogenic Effects of Dopamine on the Isolated Working Heart of Rabbit

Wakita¹

2007

J. Physiol. Sci

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“…The positive inotropic effects of dopamine in guinea pig ventricular strips [13] and rabbit papillary muscles [3] have been ascribed to both direct and indirect r-stimulation as well as a direct ~-adrenoceptor stimulation in the rabbit heart. The use of selective antagonists in the present study indicates that several receptors are involved in the positive inotropic actions of dopamine in human papillary muscle strips.…”

Section: Discussionmentioning

confidence: 99%

The inotropic effects of dopamine and its precursor levodopa on isolated human ventricular myocardium

1985

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The direct positive inotropic effects of dopamine and its precursor, levodopa, were measured using isolated, contracting human papillary muscle strips taken from patients during mitral valve replacement. Levodopa did not produce any positive inotropic effect at concentrations up to 3 X 10(-3) M. The positive inotropic effects of dopamine were observed at concentrations above 1 X 10(-5) M with the maximal effect at 3 X 10(-3) M - concentrations higher than those observed in therapy. This inotropic effect was reduced by the beta 1-selective antagonist, 1-practolol (1 X 10(-6) M); the beta 2-selective antagonist, ICI 118,551 HCl (1 X 10(-6) M); the dopamine antagonist, haloperidol (3 X 10(-6) M); the neuronal uptake inhibitor, cocaine (3 X 10(-5) M), but not by the alpha 1-antagonist, prazosin (1 X 10(-7) M). This indicates that dopamine exerts its positive inotropic effects on human heart muscle mainly through release of noradrenaline, together with possible interactions at beta- and dopamine-receptors. The maximal inotropic effect of dopamine was about 50% that of calcium (15 mM, 6.2 +/- 0.7 mN) or ouabain (1 X 10(-7) M, 5.0 +/- 0.8 mN) when measured in the same muscle strips, possibly due to the reduced cardiac noradrenaline content together with the reduced beta-receptor number in congestive heart failure. This concentration of ouabain (1 X 10(-7) M) gave almost maximal inotropy without marked toxicity; when dopamine was then added, only toxicity developed without any further increases in force of contraction. Any haemodynamic benefits of dopamine therapy in optimally digitalis-treated patients are probably due to other cardiovascular effects such as vasodilatation.

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Agents for the treatment of heart failure

Bristol¹,

Evans²

1983

Medicinal Research Reviews

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Studies on the positive inotropic effect of dopamine in the guinea-pig heart

Cited by 22 publications

References 26 publications

Inotropic, Chronotropic, and Arrhythmogenic Effects of Dopamine on the Isolated Working Heart of Rabbit

Inotropic, Chronotropic, and Arrhythmogenic Effects of Dopamine on the Isolated Working Heart of Rabbit

The inotropic effects of dopamine and its precursor levodopa on isolated human ventricular myocardium

Agents for the treatment of heart failure

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