Effectiveness of cardiac glycosides in human myocardium with and without "downregulated" beta-adrenoceptors.
We investigated the "receptor-effector-coupling" in the beta-adrenoceptor- and the Na+, K(+)-ATPase-mediated systems in nonfailing hearts and terminally failing human myocardium from patients with cardiomyopathy. The density of beta-adrenoceptors in the failing human myocardium was significantly (p less than 0.01) lower as compared with nonfailing hearts, whereas the receptor density and affinity measured by [3H]ouabain binding (cardiac glycoside receptor) was not different in either group. The maximal inotropic response to isoprenaline was significantly reduced in papillary muscle strips from failing human hearts (2.1 +/- 0.5 mN) as compared with control hearts (8.0 +/- 1.0 mN; p less than 0.05). Ouabain remained effective in both groups (6.8 +/- 1.0 vs. 5.5 +/- 0.6 mN; NS). The positive inotropic response due to extracellular Ca2+ elevation (1.8-15 mM) was studied for comparison. Maximal Ca2+ effects were reduced by 30% in failing human myocardium (7.2 +/- 0.5 mN vs. 5.1 +/- 0.8 mN, p less than 0.05). Ouabain had effectiveness (95%) similar to that of Ca2+ in nonfailing and failing human cardiac muscle. It is concluded that treatment with cardiac glycosides may still be effective in end-stage heart failure with "downregulated" beta-adrenoceptors, as judged from these in vitro studies.
Medizinische Klinik I der Universität München, F.R.G.
R H
RH
Schwinger
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M
Böhm
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E
Erdmann
D000328:Adult; D002301:Cardiac Glycosides / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D002301:Cardiac Glycosides; D011943:Receptors, Adrenergic, beta; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol