Extrakardiale Digitaliswirkungen

Lendle, L.; Mercker, H.

doi:10.1007/978-3-642-49946-3_7

Cited by 4 publications

(5 citation statements)

References 197 publications

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“…Excised arterial and venous strips contract when exposed to digitalis glycosides (1)(2)(3)(4), and generalized systemic arteriolar and venous constriction has been induced by digitalis in-anesthetized open-chest dogs on cardiopulmonary bypass (5,6). In normal human subjects digitalis glycosides elevate arterial pressure and either have little effect on or diminish cardiac output, thus augmenting the calculated systemic vascular resistance (7).…”

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confidence: 99%

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Mason¹,

Braunwald²,

Karsh³

et al. 1964

J. Clin. Invest.

304

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Although the therapeutic action of digitalis is generally agreed to result largely from its ability to stimulate the contraction of the myocardium, there has been considerable suspicion that cardiac glycosides may also act directly upon the systemic vascular bed. Excised arterial and venous strips contract when exposed to digitalis glycosides (1-4), and generalized systemic arteriolar and venous constriction has been induced by digitalis in-anesthetized open-chest dogs on cardiopulmonary bypass (5, 6). In normal human subjects digitalis glycosides elevate arterial pressure and either have little effect on or diminish cardiac output, thus augmenting the calculated systemic vascular resistance (7). More direct evidence that digitalis acts upon vascular smiiooth muscle was provided by the observation that the drug elevated systemic vascular resistance in patients on total cardiopulmonary bypass, in whom the systemic perfusion rate was held constant, and in whom the cardiac effects of the drug could not influence arterial pressure directly (8). Little information is available, however, concerning the extracardiac actions of digitalis glycosides when given in the usual clinical doses to intact human subjects. The present investigation was undertaken to characterize the effects of ouabain on a specific vascular bed, that of the forearm. The effects of the drug on both the resistance and capacitance vessels were examined in normal subjects and in patients with congestive heart failure. Materials and MethodsThe effects of ouabain were determined in 12 normal subjects, between 18 and 49 years of age, and in 6 patients with congestive heart failure, between 34 and 52 years in age. Four of these patients had rheumatic mitral

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confidence: 99%

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Mason¹,

Braunwald²,

Karsh³

et al. 1964

J. Clin. Invest.

304

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“…Work from several laboratories has demonstrated a direct effect of digitalis to increase vascular resistance. Excised arterial and venous strips contact when exposed to digitalis glycosides (Cow, 1911;Franklin, 1925;Leonard, 1957;Lendle and Mercker, 1961 glycosides cause a rise in splanchnic vascular resistance in the dog (Katz et al, 1978;Harrison et al, 1969). Stark and associates (1972) demonstrated a rise in canine skeletal muscle vascular resistance in response to acetylstrophanthidin comprising both direct and neurally mediated components.…”

Section: Discussionmentioning

confidence: 99%

Localization of the neurally mediated coronary vasoconstrictor properties of digitalis in the cat.

Somberg¹,

Kuhlman²,

Smith³

1981

Circulation Research

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SUMMARY Neural activation by digitalis has been shown to facilitate the development of cardiac arrhythmias and to mediate digitalis-induced increases in systemic and coronary resistance. Recent studies in our laboratory have implicated an area in the medulla within 2 inn of the obex as the locus for the neurally mediated arrhythmogenic properties of digitalis. To localize the site of digitalis-induced neural activation leading to increased coronary vascular resistance, 56 cats were anesthetized and an electromagnetic flow probe placed around the proximal right coronary artery. We used measurements of mean coronary flow and mean central aortic pressure and determined mean coronary vascular resistance every 6 minutes. DIGITALIS is well known to have a vasoconstrictor effect on the systemic arterial, venous, and splanchnic circulations (Ross et aL, 1960;Mason et al., 1964;Harrison et al., 1969;Katz et al., 1978). The rise in coronary vascular resistance in response to rapidly administered cardiac glycosides has been demonstrated to be mediated, in part, by the central nervous system (Vatner et al., 1971;Garan et al., 1974). Vatner et al. (1971) demonstrated that ouabain caused a rise in coronary vascular resistance in dogs when injected intravenously at a dose of 20 /ig/kg. This study and that of Hamlin et al. (1974) demonstrated a neurogenic component in the coronary vasoconstrictor effects of digitalis that could be abolished by a-adrenergic receptor blockade using phenoxybenzamine. Cross-perfusion experiments, in which the isolated head of an operative dog was perfused with digoxin-containing blood from a donor dog, thus keeping digoxin levels in the remainder of the operative dog very low, showed a degree of coronary vasoconstriction in the operative From the Cardiovascular Division,

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“…Digitalis does not act specifically on the heart; at appropriate concentrations it probably affects every living tissue in the body (Withering, 1785;Koppe, 1875;Shrager, 1957;Voh Capeller, Copeland and Stern, 1959;Somlyo, 1960;Lendle and Mercker, 1961). Wherever it has been found to act, a digitalis sensitive ion transport mechanism has been identified (Bonting, Caravaggio & Hawkins, 1962; and there is now a body of evidence that an ion transport effect mediates its therapeutic actions.…”

Section: Discussionmentioning

confidence: 99%

Cat assay for the emetic action of digitalis and related glycosides (digitoxin, digoxin, lanatoside C, ouabain and calactin)

Parsons

Summers

1971

British J Pharmacology

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Summary1. A titration assay with two end points is described for comparison of the emetic and lethal potencies of digitalis-like drugs. 2. A drug was infused at constant rate to a conscious, unrestrained cat. through an indwelling venous cannula. At the moment of vomiting the cat was rapidly anaesthetized and infusion continued at the same rate until the moment of cardiac arrest. 3. With very slow and very fast infusions, the emetic and lethal doses tended to rise. In the range between these extremes (which varied from drug to drug) they were independent of time. 4. The observations could be accounted for by analogue computation, assuming that the drugs entered an initial pool and were distributed at finite rates to receptors in the CNS (vomiting centre) and heart. 5. Half times of metabolic loss derived from this computation for digitoxin, digoxin and ouabain (17, 9 9 and 1-8 h, respectively) were in the same ratio as the threefold longer half times reported for these drugs in man. 6. When measured with infusion rates in the time independent range, the ratio of lethal to emetic doses did not vary between the drugs studied. All caused vomiting at 40% of the lethal dose. 7. From a review of the literature, the emetic and cardiotoxic actions of digitalis-like drugs appear inseparable and probably share a common biochemical mechanism. 8. It is concluded that foreseeable improvements in digitalis-like drugs are small and would depend on the elimination of any local emetic effect on gut receptors which they may have.

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Extrakardiale Digitaliswirkungen

Cited by 4 publications

References 197 publications

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Localization of the neurally mediated coronary vasoconstrictor properties of digitalis in the cat.

Cat assay for the emetic action of digitalis and related glycosides (digitoxin, digoxin, lanatoside C, ouabain and calactin)

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