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.
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1.
The three cardenolides caused the same positive inotropic effect in electrically-driven isolated atria from either reserpinized or normal guinea pigs.
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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.
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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.
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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.
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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.
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.
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1.
Die drei Pharmaka wirkten an elektrisch gereizten Vorhöfen von reserpini-sierten oder unbehandelten Meerschweinchen gleich stark positiv inotrop.
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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.
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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.
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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.
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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.
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Literatur
Baeiso, C. E., T. E. Gaffney, H. Fukusumi, J. Homes, N. O. Fowler, and E. C. Conradi: The effect of stress upon the performance of the amine-depleted heart. J. Pharmacol. exp. Ther. 156, 294 (1967).
Boyajy, L. D., and C. B. Nash: Influence of reserpine on arrhythmias, inotropic effects and myocardial potassium balance induced by digitalis materials. J. Pharmacol. exp. Ther. 148, 193 (1965).
Ciofalo, E., B. Levitt, and J. Roberts: Some factors affecting ouabain-induced ventricular arrhythmia in the reserpine-treated cat. Brit. J. Pharmacol. 30, 143 (1967).
Erlij, D., and R. Mendez: The modification of digitalis intoxication by excluding adrenergic influences on the heart. J. Pharmacol. exp. Ther. 144, 97 (1964).
Fawaz, G.: Effect of reserpine and pronethalol on the therapeutic and toxic doses of digitalis in the dog heart-lung preparation. Brit. J. Pharmacol. 29, 302 (1967).
Kilz, U., J. Schaefer, and P. A. van Zwieten: The contribution of adrenergic mechanisms to frequency potentiation and to paired stimulation in guinea pig isolated atrial tissue. Pflügers Arch, (im Druck) (1969).
Kuschinsky, K.: Über die Bindungseigenschaften von Plasmaproteinen für Herzglykoside. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. (im Druck) (1969).
— Hg. Lahetz, H. Lüllmann, and P. A. van Zwieten: Accumulation and release of 3H-digoxin by guinea-pig heart muscle. Brit. J. Pharmacol. 30, 317 (1967 a).
— H. Lüllmann, G. Schmitz u. P. A. van Zwieten: Zur Frage der Bindung von 3H-Digoxin an Herzmuskelgewebe. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 258, 297 (1967b).
— and P. A. van Zwieten: A comparison of the accumulation and release of 3H-ouabain and 3H-digitoxin by guinea pig heart muscle. Brit. J. Pharmacol. 32, 598 (1968a).
— — The uptake of 3H-ouabain and 3H-digitoxin by guinea pig atria previously extracted with glycerol. Europ. J. Pharmacol. 4, 228 (1968b).
— — The binding of 3H-digitoxigenin by guinea-pig atrial tissue. Brit. J. Pharmacol. 34, 613 (1968 c).
Lage, G. L., and J. L. Speatt: Antagonism of intravenous digitoxigenin lethality by reserpine-pretreatment in the mouse. Proc. Soc. exp. Biol. (N. Y.) 125, 580 (1967).
Levitt, B., and J. Roberts: The capacity of different digitalis materials to induce ventricular rhythm disturbances in the reserpine pretreated cat. J. Pharmacol. exp. Ther. 156, 159 (1967).
Levy, J. V., and V. Richards: Contractile and metabolic effects produced by ouabain on isolated rabbit left atria. J. Pharmacol. exp. Ther. 147, 205 (1965).
Lowry, O. H., N. J. Rosenbrough, A. L. Farr, and R. J. Randall: Protein measurement with the Folin phenol reagent. J. biol. Chem. 193, 265 (1951).
Marcus, F. J., J. Pavlovich, M. Lullin, and G. G. Kapadia: The effect of reserpine on the metabolism of 3H-digoxin in the dog and in man. J. Pharmacol. exp. Ther. 159, 314 (1968).
Mendez, D., J. Aceves, and R. Mendez: The antiadrenergic action of digitalis on refractory period of the A–V transmission system. J. Pharmacol. exp. Ther. 131, 199 (1961).
Morrow, D. H., T. E. Gaffney, and E. Braunwald: Effect of autonomic innervation and of myocardial catecholamine stores upon the cardiac action of ouabain. J. Pharmacol. exp. Ther. 140, 236 (1963).
Muscholl, E., and M. Vogt: The action of reserpine on the peripheral sympathetic system. J. Physiol. (Lond.) 141, 132 (1958).
Roberts, J., R. Ito, J. Reilly, and V. J. Cairoli: Influence of reserpine and β-TM 10 on digitalis-induced ventricular arrhythmias. Circulat. Res. 13, 149 (1963).
Spann, J. F., E. H. Sonnenblick, T. Cooper, C. A. Chidsey, V. L. Willman, and E. Braunwald: Studies on digitalis (XIV). Influence of cardiac norepine-phrine stores on the response of isolated heart muscle to digitalis. Circulat. Res. 19, 326 (1966).
Stickney, J. L., B. R. Lucchesi, and G. D. Abrams: Pharmacological alterations of the response of the mammalian heart to acetylstrophanthidin. Fed. Proc. 25, 621 (1966).
Sun, S.-C, R. S. Sohal, H. L. Colcolough, and G. E. Burch: Histochemical and electronmicroscopic studies of the effects of reserpine on the heart muscle of mice. J. Pharmacol. exp. Ther. 161, 210 (1968).
Tanz, R. D.: The action of ouabain on cardiac muscle treated with reserpine and dichloroisoproterenol. J. Pharmacol. exp. Ther. 144, 205 (1964).
—, and S.M. Marcus: Influence of endogenous cardiac catecholamine depletion on the force and rate of isolated heart preparations and their response to ouabain. J. Pharmacol. exp. Ther. 151, 38 (1966).
van Zwieten, P. A.: Der Einfluß von adrenergen Pharmaka und von Val5-Hypertensin II-amid auf die mittels 86Rb gemessene Membranpermeabilität am isolierten Herzvorhof von Meerschweinchen. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 261, 441 (1968 a).
— The influence of cholinergic drugs on 86Rb efflux in isolated atrial tissue. Europ. J. Pharmacol. 5, 49 (1968b).
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Kuschinsky, K., van Zwieten, P.A. (1969). Über das Verhalten von Digoxin, Digitoxin und Digitoxigenin in isoliertem Herzgewebe und im Plasma von Meerschweinchen nach Reserpin-Vorbehandlung. In: Habermann, E., et al. Naunyn Schmiedebergs Archiv für Pharmakologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-39718-3_37
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