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Über das Verhalten von Digoxin, Digitoxin und Digitoxigenin in isoliertem Herzgewebe und im Plasma von Meerschweinchen nach Reserpin-Vorbehandlung

  • Klaus Kuschinsky
  • P. A. van Zwieten
Chapter

Zusammenfassung

Die positiv-inotrope Wirkung, die Aufnahme in isolierte Vorhöfe und die Eiweißbindung im Plasma wurden für Digoxin, Digitoxin und Digitoxigenin an normalen und mit Reserpin vorbehandelten Meerschweinchen untersucht. Die Versuche wurden zum Teil mit Tritium-markierten Cardenoliden durchgeführt.
  1. 1.

    Die drei Pharmaka wirkten an elektrisch gereizten Vorhöfen von reserpini-sierten oder unbehandelten Meerschweinchen gleich stark positiv inotrop.

     
  2. 2.

    Die Aufnahme von 3H-Digoxin in isolierte Vorhöfe wurde von einer Reserpin-Vorbehandlung der Spendertiere nicht beeinflußt. Nach einer Reserpin-Vorbehandlung nahmen die Vorhöfe jedoch etwa 20% mehr 3H-Digitoxin oder 3H-Digitoxigenin auf.

     
  3. 3.

    Die Eiweißbindung von 3H-Digoxin im Plasma wurde von einer Reserpin-Vorbehandlung der Meerschweinchen nicht beeinflußt. 3H-Digitoxin und 3H-Digitoxigenin wurden dagegen von Plasma-Eiweißen reserpinisierter Meerschweinchen stärker gebunden als von denen unbehandelter Kontrolltiere.

     
  4. 4.

    Das Plasma von mit Reserpin vorbehandelten Meerschweinchen zeigte dieselbe Osmolalität, Refraktion und Gesamteiweißkonzentration wie das Plasma unbehandelter Kontrolltiere. Auch das Elektropherogramm des Plasmas und der Hämatokrit des Blutes wurden durch die Reserpin-Vorbehandlung nicht verändert.

     
  5. 5.

    Wahrscheinlich erhöht die Vorbehandlung mit Reserpin durch einen bisher unbekannten Mechanismus die Bindungsfähigkeit des Albumin für Cardenolide. Ein ähnlicher Mechanismus könnte die verstärkte Aufnahme der Substanzen durch den Herzmuskel erklären.

     

Schlüsselwörter

Herzglykoside Reserpin Aufnahme im Gewebe Eiweißbindung Positiv inotrope Wirkung 

Summary

The positive inotropic effect, the tissue uptake and the binding to plasma proteins were determined in isolated atria and in plasma of normal and reserpinized guinea pigs for digoxin, digitoxin and digitoxigenin. Some of the experiments were carried out with tritium-labelled cardenolides.
  1. 1.

    The three cardenolides caused the same positive inotropic effect in electrically-driven isolated atria from either reserpinized or normal guinea pigs.

     
  2. 2.

    Pretreatment of the animals with reserpine did not influence the uptake of 3H-digoxin in isolated atria. After pretreatment with reserpine, however, approximately 20% more 3H-digitoxin and 3H-digitoxigenin were taken up.

     
  3. 3.

    Pretreatment of the guinea pigs with reserpine did not influence the binding of 3H-digoxin to plasma proteins. The binding of 3H-digitoxin and 3H-digitoxigenin to proteins, however, was increased in plasma of reserpinized guinea pigs in comparison with that of untreated control animals.

     
  4. 4.

    The plasma of reserpinized guinea pigs showed the same osmolality, refraction and total protein content as the plasma of untreated control animals. The plasma electropherogram and also the haemotacrit value of the blood proved to be unaltered in reserpinized guinea pigs.

     
  5. 5.

    Probably, the pretreatment with reserpine increase the binding capacity of plasma albumin for cardenolides by a mechanism so far unknown. A similar mechanism might cause the increased accumulation by heart muscle tissue.

     

Key-Words

Cardiac Glycosides Reserpine Tissue Uptake 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1969

Authors and Affiliations

  • Klaus Kuschinsky
    • 1
  • P. A. van Zwieten
    • 1
  1. 1.Institut für PharmakologieUniversität KielKielDeutschland

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