Problems in the use of digitalis in the management of congestive heart failure

McIntosh, Henry D.; Morris, James J.

doi:10.1016/s0033-0620(65)80027-5

Cited by 15 publications

(7 citation statements)

References 86 publications

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“…The findings in this study are also pertinent to the widely accepted notion that as the quantity of digitalis administered approaches that which produces toxicity, the inotropic effects of the additional increments of the drug become progressively less (42,43). When 40.3 ,ug per kg ouabain (80%o of the dose required to produce initial toxicity) has been administered, myocardial contractile force has increased by 48%o of control.…”

Section: Resultsmentioning

confidence: 52%

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Studies on digitalis. 13. A comparison of the effects of potassium on the inotropic and arrhythmia-producing actions of ouabain.

Williams¹,

Klocke²,

Braunwald³

1966

J. Clin. Invest.

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Although it is generally recognized that digitalis-induced arrhythmias can be suppressed by the administration of potassium (1-3), it is not clear whether the potassium ion also influences the positive inotropic effect exerted by the glycosides on the intact mammalian heart. Clarification of this problem is important in the understanding of the interrelationships between the actions of glycosides and potassium, and is clinically significant in view of the frequency with which potassium is administered to patients who are or have been receiving digitalis. Accordingly, the present investigation was undertaken to determine the manner in which potassium suppression of ouabaininduced arrhythmias affects the augmentation of ventricular contractile force produced by the administration of the glycoside. MethodsTen mongrel dogs, weighing between 10 and 25 kg, were anesthetized with intravenous sodium pentobarbital (35 mg per kg) and ventilated with a positive displacement pump that was supplied with a mixture of room air and 100% 02. The right ventricle was exposed through a median sternotomy, a Walton-Brodie strain gauge arch (4) was sutured to the right ventricle, and the muscle segment beneath the gauge was stretched approximately 50% beyond its initial length. This maneuver allows recording of the changes in contractile force of the segment of myocardium between the points of attachment of the gauge despite some changes in right ventricular dimensions (5). Heparin, 5 mg per kg, was administered intravenously. With a compressed air-blood reservoir that was connected to a femoral artery through a large bore cannula, mean arterial pressure was maintained constant despite any changes in blood volume that might have occurred as a consequence of bleeding or blood withdrawal for plasma K concentration. Body tempera-* Submitted for publication June 9, 1965; accepted November 26, 1965. f Address requests for reprints to Dr. Eugene Braunwald, Cardiology Branch, National Heart Institute, Bethesda, Md. 20014. ture was monitored with a thermistor probe placed in the superior vena cava and was maintained constant with heating pads. Femoral arterial pressure was measured with a Statham P23D strain gauge transducer, and arterial blood was withdrawn at intervals for determinations of plasma K by flame photometry. Right ventricular contractile force, arterial pressure, and a limb lead of the electrocardiogram were recorded continuously on a direct-writing oscillograph. In two of the ten animals the sinoatrial node was crushed and heart rate maintained constant by stimulating the right atrium at a rate just above the spontaneous rate. Two animals had undergone bilateral adrenalectomy 1 week before the experiment and were then maintained on steroid replacement therapy.After control measurements, an intravenous dose of ouabain, 30 tzg per kg, was administered over a 5-minute period. Ten to 15 minutes later a constant infusion of ouabain, 30 jzg per kg per hour, was begun and was continued for the remainder of the experiment. Ouabai...

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Section: Resultsmentioning

confidence: 52%

“…A still greater increase of contractile force, to a level averaging 84%o above control, occurred when toxicity was suppressed and an additional 15.6 ,ug per kg ouabain was administered. Thus, these observations do not support the view (42,43) that the inotropic effects of additional glycoside are minimal as the toxic dose is approached.…”

Section: Resultsmentioning

confidence: 60%

Studies on digitalis. 13. A comparison of the effects of potassium on the inotropic and arrhythmia-producing actions of ouabain.

Williams¹,

Klocke²,

Braunwald³

1966

J. Clin. Invest.

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“…In this circumstance, the term 'PAT with block' has been used. 25 The importance of PAT with block induced by digitalis was emphasized because the arrhythmia was often found in serious underlying heart disease with a high mortality.22' 32 Although the frequent occurrence of digitalis-induced PAT with block is emphasized repeatedly, its average incidence is only about 10%4 of the total digitalis-induced cardiac arrhythmias.2' 3,11,12,14,[22][23][24][25][26][27][28] This author2 found twelve instances of atrial tachycardia with A-V block (Fig. 3) and three instances without A-V block among 180 cases with digitalis intoxication.…”

Section: Cardiac Manifestationsmentioning

confidence: 99%

Digitalis intoxication

Chung

1972

Postgraduate Medical Journal

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“…The manner in which patients with altered thyroid states respond to cardiac glycosides has long been of interest (5,31,32). All workers who have examined the problem agree that both hypoand hyperthyroid heart muscle respond to the glycoside (5, [33][34][35]; however, analysis of the problem in patients and intact experimental animals is complicated by the facts that the absorption and the turnover of the drug (36), as well as the fraction of the cardiac output which enters the coronary circulation (37,38), may all be influenced by alterations in the thyroid state, making it difficult to deliver a known concentration of drug to the myocardium.…”

Section: Mals (Figs 4 and 5)mentioning

confidence: 99%

Influence of the Thyroid State on the Intrinsic Contractile Properties and Energy Stores of the Myocardium*

Buccino¹,

Spann²,

Pool³

et al. 1967

J. Clin. Invest.

377

100

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Abstract. The intrinsic contractile properties of isolated cat papillary muscles and myocardial high energy phosphate stores were examined at three levels of thyroid activity and correlated with hemodynamic measurements in the intact animal. In addition, the relationship of thyroid state to endogenous norepinephrine stores and myocardial responsiveness to certain inotropic in-.terventions were studied. In muscles from hyperthyroid cats, the velocity of shortening and the rate of tension development were markedly augmented, while duration of active state was decreased, compared to euthyroid muscles. These findings occurred in the presence and absence of intact norepinephrine stores and over a wide range of temperature and contraction frequency. The opposite changes occurred in muscles from hypothyroid cats. Isometric tension was slightly higher in muscles from hyperthyroid and lower in muscles from hypothyroid cats. The inotropic response to both norepinephrine and strophanthidin varied inversely with the level of thyroid state and allowed all three groups of muscles to reach a common ceiling of isometric tension regardless of thyroid state. Creatine phosphate and adenosine triphosphate stores were intact at all three levels of thyroid state. Thus, the level of thyroid activity profoundly affects the intrinsic contractile state of cardiac muscle, independent of both norepinephrine stores and alterations in high energy phosphate stores, and, in addition, modifies the responsiveness of cardiac muscle to inotropic agents.

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Problems in the use of digitalis in the management of congestive heart failure

Cited by 15 publications

References 86 publications

Studies on digitalis. 13. A comparison of the effects of potassium on the inotropic and arrhythmia-producing actions of ouabain.

Studies on digitalis. 13. A comparison of the effects of potassium on the inotropic and arrhythmia-producing actions of ouabain.

Digitalis intoxication

Influence of the Thyroid State on the Intrinsic Contractile Properties and Energy Stores of the Myocardium*

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