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Kardiale Wirkungen von Adenosin

Cardiac effect of adenosine: Mechanism of action, pathophysiological role and clinical implications

Wirkungsmechanismus, pathophysiologische und klinische Bedeutung

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Summary

Adenosine has a negative inotropic effect in cardiacatrial preparations (“direct” negative inotropic effect). This effect is probably due to an activation of a potassium outward current which shortens the action potential duration and hence reduces the force of contraction. A pertussis toxin-sensitive N-protein is involved in the signal transduction from the adenosine receptor to atrial potassium channels. Inventricular cardiac preparations adenosine has no negative or even a weak positive inotropic effect, but it reduces the force of contraction in the presence of cAMP-increasing agents such as isoprenaline (“indirect” negative inotropic effect). This effect is due to an inhibition of the slow Ca2+ inward current which has previously been enhanced by an increase in the cellular cAMP content. This “indirect” negative inotropic effect of adenosine is also present in the human heart. Since increased amounts of adenosine are released during cardiac stimulation via β-adrenoceptors, the “indirect” effect might protect the heart against excessive stimulation by catecholamines. In addition, adenosine has negative chronotropic actions and prolongs AV conduction by an activation of potassium channels or an inhibition of the slow Ca2+ inward current (AV node). Cardiac bradyarrhythmias in hypoxia have been attributed to an increased formation and release of adenosine. Furthermore, adenosine has been shown to terminate supraventricular tachycardias involving the AV node. Since it has a very short duration of action it might prove safe and hence advantageous to conventional therapy in the treatment of supraventricular tachycardias.

Zusammenfassung

Zusammenfassend läßt sich sagen, daß Adenosin am Vorhof negativ inotrop wirkt (direkter negativ inotroper Effekt). Am Ventrikel wirkt Adenosin nur bei Erhöhung des zellulären cAMP-Gehaltes durch Stimulation der Adenylatcyclase oder Hemmung der Phosphodiesterase negative inotrop (indirekter negative inotroper Effekt). Diese Wirkung ist von einer Abnahme des langsamen Ca2+-Einwärtsstromes begleitet. Ob diese Abnahme mit einer Hemmung der Adenylatcyclase erklärt werden kann oder ob Mechanismen, die der cAMP-Bildung nachgeschaltet sind (z.B. Hemmung cAMP-abhängiger Proteinkinasen, Aktivierung von Proteinphosphatasen), eine Rolle spielen, ist bisher umstritten. Der indirekte negativ inotrope Effekt konnte kürzlich auch an isoliertem menschlichen Ventrikelmyokard nachgewiesen werden, so daß Adenosin möglicherweise auch am menschlichen Herzen eine Rolle als physiologischer Feedback-Hemmstoff bei exzessiver Katecholaminstimulation und bei Hypoxie spielen könnte. Diese Hemmung einer Stimulation kardialer β-Adrenozeptoren könnte eine antiarrhythmische Wirkung bei katecholamininduzierten Tachyarrhythmien bewirken. Eine defekte adenosinvermittelte Regulation des Herzens könnte schließlich auch eine Bedeutung in der Pathogenese von Herzerkrankungen wie der hypertrophen Kardiomyopathie haben. Hierüber liegen allerdings keine klinischen oder experimentellen Daten vor. Andererseits wirkt Adenosin negativ chronotrop und dromotrop und vermittelt wahrscheinlich bradykarde Herzrhythmusstörungen während myokardialer Hypoxie. Entsprechend seiner negativ dromotropen Wirkung eignet es sich zur Therapie von supraventrikulären Tachykardien mit Beteiligung des AV-Knotens. Seine kurze Wirkdauer läßt es als vorteilhaft gegenüber einer konventionellen Therapie mit Ca2+-Antagonisten erscheinen.

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Abbreviations

s:

Sekunde

mN:

Millinewton

mV:

Millivolt

cAMP:

cyclisches Adenosin-3′,5′-monophosphat

cGMP:

cyclisches Guanosin-3′,5′-monophosphat

PIA:

(-)-N6-Phenylisopropyladenosin

NECA:

5′-N-Äthylcarboxamidadenosin

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  1. Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, Germany

    M. Böhm

  2. Klinikum Großhadern, Medizinische Klinik I der Universität München, Marchioninistraße 15, D-8000, München 70

    M. Böhm

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Böhm, M. Kardiale Wirkungen von Adenosin. Klin Wochenschr 65, 487–499 (1987). https://doi.org/10.1007/BF01721034

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