Effect of Reserpine and Pronethalol on the Therapeutic and Toxic Actions of Digitalis in the Dog Heart‐lung Preparation

Fawaz, G.

doi:10.1111/j.1476-5381.1967.tb01961.x

Cited by 12 publications

(5 citation statements)

References 10 publications

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“…If this were the case then little increase in contractility would have been observed with ouabain after beta receptor blockade, when in fact the increases were actually far greater than in the conscious dogs without propranolol. This finding in the intact conscious dog supports the conclusion derived from other studies (20,(58)(59)(60)(61)(62) that cardiac glycosides act independently of cardiac catecholamine stores.…”

Section: Discussionsupporting

confidence: 82%

Effects of cardiac depression and of anesthesia on the myocardial action of a cardiac glycoside

Vatner¹,

Higgins²,

Patrick³

et al. 1971

J. Clin. Invest.

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A B S T R A C T The effects of ouabain (G-strophanthin) 20 /Ag/kg, on left ventricular (LV) pressure (P), diameter (D), velocity of contraction (dD/dt), and dP/dt were studied in conscious dogs instrumented with ultrasonic diameter gauges and miniature pressure gauges. The effects of ouabain were compared on separate occasions in the same dogs after cardiac depression with propranolol, 3.0 mg/kg, and also after general anesthesia with Na pentobarbital, 30 mg/kg. Maximal pressor effects were observed in the first 10 min, but maximal effects on the contractile state occurred at 30 min after ouabain. At this time, in conscious dogs, ouabain had increased LV isolength systolic pressure by 5%, LV isolength velocity by only 9%, and LV (dP/dt)/P by 21%, while end systolic diameter (ESD) decreased slightly and end diastolic diameter (EDD) and heart rate (HR) were unchanged. After anesthesia, ouabain increased LV systolic pressure by 8%, velocity 32%, (dP/dt)/P by 47%, and ESD decreased by 1.2 mm while EDD rose slightly and HR fell by 26 beats/min. Returning HR to control with atrial pacing decreased EDD 0.9 mm below control. After cardiac depression with propranolol, ouabain caused responses similar to those observed in the anesthetized dogs. Thus, the cardiac glycoside was found to exert only minor inotropic effects on the nonfailing heart of conscious dogs but far more striking inotropic responses in the anesthetized state.

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Section: Discussionsupporting

confidence: 82%

Effects of cardiac depression and of anesthesia on the myocardial action of a cardiac glycoside

Vatner¹,

Higgins²,

Patrick³

et al. 1971

J. Clin. Invest.

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“…Alternate explanations seem more likely for some of these observations, while others could not be confirmed by subsequent investigators. Treatment with reserpine before exposure to cardiac glycosides has been found by many (2, 16-20) though not all (5, 14, 28,31) investigators to reduce the arrhythmogenir potential of these agents. Any ability of previously given reserpine to counteract the arrhythmogenic potential of digitalis does not allow the conclusion that in the untreated animal or patient digitalis causes arrhythmias in part by releasing catecholamines.…”

Section: Discussionmentioning

confidence: 99%

“…Dichloroisoproterenol, a partial beta-receptor agonist rather than a pure antagonist, has been reported not to influence (21, 33) or to decrease (4, 21) the positive inotropic effect of cardiac glycosides. Pronethalol, a purer beta-receptor antagonist, caused no major changes in the positive inotropic action of cardiac glycosides on rabbit atria (34), on the dog heart-lung preparation (28) and on the dog heart in situ (32). In the latter preparation, the inotropic effect of strospeside was increased after doses of pronethalol which depressed myocardial contractility (45).…”

Section: Discussionmentioning

confidence: 99%

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Beta-Receptor Blockade and Myocardial Effects of Cardiac Glycosides

Koch‐Weser

1971

Circulation Research

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Because of suggestions that norepinephrine release from cardiac sympathetic nerves contributes to the myocardial action of digitalis, the effect of betareceptor blockade on these actions was determined. I C H M propranolol did not alter the basal contractility of isolated kitten papillary muscles or of atrial strips from kittens, guinea pigs, rabbits, dogs, and chickens but decreased by 85% their inotropic response to norepinephrine released by tyramine or highintensity electrical stimulation. The same concentration of propranolol had no effect on cumulative inotropic concentration-effect curves for ouabain, acetylstrophanthidin, and digoxin in these preparations. Presence of propranolol did not modify the actions of cardiac glycosides on the time course of isometric contraction. Beta-receptor blockade was without effect on decreases in active tension and increases in resting tension induced by toxic concentrations of cardioactive steroids. The frequency of digitalis-induced automaticity in guinea pig atrial strips and kitten papillary muscles was significantly decreased by propranolol, presumably because of its direct electrophysiologic actions. Exposure of cat hearts to digoxin in vivo and to ouabain in vitro had no effect on myocardial norepinephrine concentrations. It is concluded that release of myocardial norepinephrine plays no role in the actions of cardiac glycosides on the heart. KEY WORDSisolated heart muscle propranolol ouabain inotropic concentration-effect curves acetylstrophanthidin contracture myocardial automaticity myocardial norepinephrine rabbits dogs chickens cats guinea pigs• During the past decade many investigators have suggested that cardiac glycosides release myocardial norepinephrine and that this release contributes to their actions on the mechanical and electrical performance of the heart (1-10). This theory has been based on findings of lowered myocardial norepineph-From the rine concentration after exposure to cardiac glycosides (1, 9,(11)(12)(13), of decreased ability of cardiac glycosides to enhance myocardial contractility (3-5, 7, 10, 14, 15) or to induce arrhythmias (2, 16-20) after pretreatment with reserpine, and of interference by betareceptor antagonists with positive inotropic (4, 6, 21) or arrhythmogenic (6, 16, 22-28) actions of cardiac glycosides. Other investigators have not confirmed the depletion of myocardial norepinephrine by cardiac glycosides (10, 18,29) or any decrease in their positive inotropic effect after reserpine (

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“…Our results are in agreement with several studies (SPA" et al. 1966;FAWAZ 1967;SIMAAN et al 1968;CIOFALO 1970), which have failed to document a close relationship between myocardial catecholamine content and cardiac glycoside response.…”

Section: Discussionmentioning

confidence: 99%

Effect of Reserpine, Desipramine and Phenytoin on Digoxin Induced Arrhythmias and Myocardial Uptake of Digoxin in Guinea Pigs

Allonen

Iisalo

Nuortio

1975

Acta Pharmacologica et Toxicologica

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Digoxin was infused intravenously 27.5 μg/min. to guinea pigs. By means of the ECG doses of digoxin needed to cause ventricular extrasystoles (VES), ventricular fibrillation (VF), and asystole (AS) were determined in a control group without any premedication. Three groups were given a pre‐treatment with desipramine, phenytoin and reserpine. After AS digoxin concentrations in the heart muscle and in the kidneys were determined by radioimmunoassay. The concentrations of adrenaline and noradrenaline were also determined in these tissues. After reserpine and phenytoin the doses of digoxin needed to induce VF and AS were increased. Desipramine had no effect on digitalis‐induced arrhythmias. The relative uptake of digoxin in the heart muscle was decreased after all of the three premedications; there was no change in the kidney. The tissue catecholamine concentrations were decreased after reserpine and desipramine, but remained unchanged after phenytoin. The lethal dose of digoxin seemed not to correlate to the myocardial digoxin concentration after different premedications. The mechanism of the uptake in the heart muscle seemed to be different from that in the kidney. There was no correlation between the catecholamine concentration in myocardium and the ar‐rhythmogenic effect of digoxin in the different groups.

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Effect of Reserpine and Pronethalol on the Therapeutic and Toxic Actions of Digitalis in the Dog Heart‐lung Preparation

Cited by 12 publications

References 10 publications

Effects of cardiac depression and of anesthesia on the myocardial action of a cardiac glycoside

Effects of cardiac depression and of anesthesia on the myocardial action of a cardiac glycoside

Beta-Receptor Blockade and Myocardial Effects of Cardiac Glycosides

Effect of Reserpine, Desipramine and Phenytoin on Digoxin Induced Arrhythmias and Myocardial Uptake of Digoxin in Guinea Pigs

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