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Apparent superiority of H2-receptor stimulation and simultaneousβ-blockade over conventional treatment withβ-sympathomimetic drugs in post-acute myocardial infarction: Cardiac effects of impromidine — a new specific H2-receptor agonist — in the surviving catecholamine-insensitive myocardium

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Abstract

Left ventricular infarction (AMI) was produced in experimental animals and the contractile response to β-adrenergic and H2-histaminergic stimulation by isoproterenol and impromidine tested in the isolated perfused heart preparation. Adenylate cyclase activity as well as binding characteristics of [3H]-dihydroalprenolol ([3H]-DHA), [3H]-methyl-tiotidine ([3H]-TIOT) and [3H]-quinuclidinyl benzilate ([3H]-QNB) to cardiacβ 1-, H2- and cholinergic muscarinic receptors were determined in sarcolemmal membrane preparations of the right ventricle of the same hearts. In addition, an attempt was made to elucidate the therapeutic value of post-AMI treatment with impromidine in the presence and absence ofβ-sympathomimetic, in contrast to administration of prenalterol and the conventional therapy with β-sympathomimetic drugs, e.g. dobutamine. Three days post-AMI the dose-response curve for isoproterenol of right ventriculardP/dt max was significantly depressed, while the inotropic effect of impromidine was not impaired. Stimulation of adenylate cyclase activity by isoproterenol was reduced by 80% whereas impromidine and NaF stimulation rates were unaltered. Receptor-binding studies indicated a 90% loss and 10-times lowered affinity (K D) of the remaining β-receptors while specific [3H]-TIOT- and [3H]-QNB-binding was unchanged.

Administration of dobutamine increased mortality rates and extension of infarct size, led to a further decrease in contractile response to isoproterenol, induced complete insensitivity of adenylate cyclase to isoproterenol stimulation and caused pronounced additional reduction of number and affinity of [3H]-DHA-binding sites. In contrast, all above alterations were prevented by treatment with either prenalterol or combined administration of impromidine plus metoprolol. It is concluded, that these alterations in the non-ischemic, uninvolved myocardium post-AMI are the result of catecholamine-induced specific damage of sarcolemmal β-receptors. Furthermore, treatment with H2-agonists in combination with β-blocking agents may have beneficial effects, whereas conventional therapy with β-sympathomimetic drugs tends to worsen the already depressed function of the β-adrenergic stimulation mechanism.

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Author notes

  1. Claus D. Heidecke

    Present address: Dept. of Surgery, Brigham and Women's Hospital, 75 Francis St., 02115, Boston, MA, USA

Authors and Affiliations

  1. Ist Department of Medicine, Klinikum rechts der Isar, Technical University, Ismaninger Str. 22, D-8000, Munich 80, Germany

    Gert Baumann, Stephan B. Felix, Claus D. Heidecke, Gotthard Rieß, Ursula Loher, Liesel Ludwig &  Hans Blömer

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  1. Gert Baumann
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Additional information

Supported by grants Ba 666/1 and Ba 666/2-2 from the Deutsche Forschungsgemeinschaft (DFG).

Data presented in this paper are part of a doctoral thesis by Dr S.B. Felix.

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Baumann, G., Felix, S.B., Heidecke, C.D. et al. Apparent superiority of H2-receptor stimulation and simultaneousβ-blockade over conventional treatment withβ-sympathomimetic drugs in post-acute myocardial infarction: Cardiac effects of impromidine — a new specific H2-receptor agonist — in the surviving catecholamine-insensitive myocardium. Agents and Actions 15, 216–228 (1984). https://doi.org/10.1007/BF01972352

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