Summary
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 3×10−3 M. The positive inotropic effects of dopamine were observed at concentrations above 1×10−5 M with the maximal effect at 3×10−3 M — concentrations higher than those observed in therapy. This inotropic effect was reduced by the β1 antagonist, 1-practolol (1×10−6 M); the β2 antagonist, ICI 118,551 HCl (1×10−6 M); the dopamine antagonist, haloperidol (3×10−6 M); the neuronal uptake inhibitor, cocaine (3×10−5 M), but not by the α1, prazosin (1×10−7 M). This indicates that dopamine exerts its positive inotropic effects on human heart muscle mainly through release of noradrenaline, together with possible interactions at β-and dopamine-receptors. The maximal inotropic effect of dopamine was about 50% that of calcium (15 mM, 6.2±0.7 mN) or ouabain (1×10−7 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 β-receptor number in congestive heart failure. This concentration of ouabain (1×10−7 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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Abbreviations
- EC50 :
-
half-maximal effective concentration
- mN:
-
millinewton
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This study was carried out using human heart samples provided by: Prof. E. Kreuzer, Dr. B. Kemkes, Dr. C. Weinhold, Herzchirurgische Klinik der Universität, Klinikum Großhadern, and Dr. K. Holper, Dr. W. Klövekorn, Herzchirurgische Klinik der Deutschen Herzzentrums, München
Supported by the Deutsche Forschungsgemeinschaft (Er 65/4-4)
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Brown, L., Lorenz, B. & Erdmann, E. The inotropic effects of dopamine and its precursor levodopa on isolated human ventricular myocardium. Klin Wochenschr 63, 1117–1123 (1985). https://doi.org/10.1007/BF02291093
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DOI: https://doi.org/10.1007/BF02291093