Studies on Digitalis. Ix. Effects of Ouabain on the Nonfailing Human Heart

Mason, Dean T.; Braunwald, Eugene

doi:10.1097/00132586-196410000-00023

Cited by 20 publications

(23 citation statements)

References 7 publications

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“…But MacKenzie (1910) clearly appreciated the positive inotropic effect of digoxin and Lewis (1946) in his later writings believed digitalis to be of value in patients in sinus rhythm. Other physicians such as Christian (1922), Luten (1924) and Marvin (1927) More recent studies have established that cardiac glycosides given acutely to either the failing or non-failing heart are inotropic (Braunwald et al, 1961;Mason & Braunwald, 1963;Sonnenblick et al, 1966;Weissler et al, 1966). The drugs also cause an increase in systemic vascular resistance (Mason & Braunwald, 1964) although this effect is less evident if the drug is given slowly (DeMots et al, 1978).…”

Section: Historymentioning

confidence: 99%

The role of digitalis in the future.

Pa¹

1984

Brit J Clinical Pharma

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Cardiac glycosides exert an acute positive inotropic effect on the normal and failing heart. Recent evidence establishes that the positive inotropic effect is maintained over several months in many patients. The effectiveness of long‐term treatment with cardiac glycosides in relieving symptoms is less certain; only a small subset of patients benefits. An effect on mortality is not established. The use of digoxin in the treatment of mild heart failure is questionable since the drug has serious side‐effects and the efficacy in patients already taking diuretics has not been established. The use of glycosides in the treatment of severe chronic heart failure is being challenged because of the availability of powerful diuretics, new vasodilators and alternative positive inotropes.

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Section: Historymentioning

confidence: 99%

The role of digitalis in the future.

Pa¹

1984

Brit J Clinical Pharma

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“…Standard cardiac catheter-manometer systems are not believed to be suitable for this type of analysis. [6][7][8] Circulation, Volume XLIV, July 1971 In calculating (dp/dt)/CPIP, it is important to point out that the dp/ dt used in this ratio is that which occurs simultaneously with CPIP and is not necessarily the peak dp/dt. For example, in figure 12, the relation between dp/dt and developed ventricular pressure in a single patient is shown during isovolumic contraction in a representative systole in both the control period and following isoproterenol administration.…”

Section: Assessment Of Contractilitymentioning

confidence: 99%

Assessment of Cardiac Contractility

et al. 1971

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SUMMARYIt was considered that the relationship between dp/dt and simultaneously developed pressure during the course of isovolumic contraction might afford a more accurate measure of contractility than the maximum rate of intraventricular pressure rise (peak dp/dt). In six cat papillary muscles contracting isometrically from any given preload, the ratio of the rate of tension development (dT/dt) to simultaneously occurring isometric tension always varied directly with the contractile state. This ratio rose slightly as preload was increased, but it was not affected by changes in afterload. In 17 experiments in an intact canine heart preparation in which left ventricular end-diastolic pressure was constant, dp/dt at any given pressure during isovolumetric contraction again was observed to be a function of the contractile state when the latter was enhanced by norepinephrine and acetylstrophanthidin. High-fidelity left ventricular pressures and dp/dt were recorded throughout isovolumic contraction in eight patients. Isoproterenol and exercise raised the level of dp/dt at any given pressure prior to ejection. Interventions known to alter ventricular loading but not to influence the contractile state, such as elevation of ventricular end-diastolic pressure by leg raising and increases in aortic pressure induced by methoxamine, did not influence this relation significantly. In conclusion, the determination of dp/dt and intraventricular pressure throughout isovolumic contraction in the presence of variable arterial pressure and small changes of preload provides a useful, simple, and experimentally verified approach to the assessment of alterations of the contractile state of the heart in intact man.

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“…Cardiac glycosides have been shown to elevate systemic vascular resistance (27) and arterial pressure (28) and to increase-the velocity of myocardial contraction, as reflected in augmentations of the rate of rise of intraventricular pressure (29), mean systolic ejection rate (30), and the rate of movement of radiopaque markers on the ventricles (10). These hemodynamic changes would tend to increase MVo2 and in the presence of coronary artery disease without heart failure could lead to myocardial ischemia.…”

Section: Fig 1 Effects Of Acetylstrophanthidin (Acs)mentioning

confidence: 99%

Studies on digitalis. XVI. Effects on myocardial oxygen consumption.

Covell¹,

Braunwald²,

Ross³

et al. 1966

J. Clin. Invest.

160

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The effects of cardiac glycosides on myocardial oxygen consumption (MVo2) have been investigated extensively, and although the results of these studies have not been entirely uniform, it is now generally considered that these agents are "the only drugs which increase the force of contraction of the myocardium without at the same time increasing oxygen consumption" (1). The finding in previous investigations that digitalis does not increase MVo2 (2-8) would not appear to be compatible with observations that the glycosides increase the velocity of myocardial fiber shortening (9, 10), since recent studies have suggested that the latter variable is an important determinant of MVo2 (11,12). These considerations prompted an examination of the effect of acetylstrophanthidin on MVo2 in a preparation that allowed control of hemodynamic variables other than contraction velocity that can significantly influence MVo2. MethodsExperiments were performed on eight dogs weighing 15.5 to 17.2 kg and anesthetized with morphine, 2.8 mg per kg; chloralose, 96 mg per kg; and urethane, 620 mg per kg. The chest was entered through a sternal splitting incision, and ventilation was maintained with a Harvard respiratory pump, using 100%o 02. Heparin (500 U per kg) was administered. The venae cavae were then cannulated, and the venous return was diverted into a reservoir, from which bypass of the right side of the heart was achieved with an occlusive roller pump, as described in detail previously (12). The pump supplied blood to the pulmonary artery through a cannula inserted via the right ventricular outflow tract; the right ventricle was therefore empty and performing no external work. Fresh blood obtained from donor dogs and exchanged with that of the experimental animal was used to prime the reservoir and circuit. Mean systemic arterial pressure was regulated by a reservoir connected to a com-* Submitted for publication April 25, 1966; accepted June 16, 1966. tAddress requests for reprints to Dr. Eugene Braunwald, Cardiology Branch, National Heart Institute, Bethesda, Md. 20014. pressed air circuit and attached by large bore cannulae to the femoral arteries. The sino-atrial node was crushed, and heart rate was maintained constant by electrical stimulation 1 of the right atrium or ventricle.Stroke volume could therefore be controlled by maintaining the output of the pump constant.A flow transducer was placed around the ascending aorta, and instantaneous aortic blood flow was measured with a gated-sine wave electromagnetic flowmeter.2 Left ventricular pressure was measured with a Statham P23Db pressure transducer attached directly to a largebore metal cannula that was inserted through the the ventricular apex. Central aortic pressure was measured through a similar cannula inserted into the aortic arch through the left subclavian artery. The first derivative (dp/dt) of the left ventricular pressure pulse was determined with an analogue differentiating circuit 3 In two hearts the effects of acetylstrophanthidin were studied at high...

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Studies on Digitalis. Ix. Effects of Ouabain on the Nonfailing Human Heart

Cited by 20 publications

References 7 publications

The role of digitalis in the future.

The role of digitalis in the future.

Assessment of Cardiac Contractility

Studies on digitalis. XVI. Effects on myocardial oxygen consumption.

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