Studies on Myocardial Metabolism. V. The Effects of Lanatoside-C on the Metabolism of the Human Heart 1

Blain, John M.; Eddleman, E.E.; Siegel, A.; Bing, Richard J.

doi:10.1172/jci103280

Cited by 42 publications

(10 citation statements)

References 20 publications

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“…The finding in previous investigations that digitalis does not increase MVo2 (2)(3)(4)(5)(6)(7)(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.…”

mentioning

confidence: 91%

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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mentioning

confidence: 91%

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

Covell¹,

Braunwald²,

Ross³

et al. 1966

J. Clin. Invest.

160

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“…Cardiac medications included digitalis and thiazides; the latter have been reported to raise blood pyruvate levels (18). Blain, Eddleman, Siegel, and Bing (19) indicated that digitalization had no effect on lactate and pyruvate metabolism. In most cases no premedication was necessary; in a few, 1 ml of a mixture of meperidine (25 mg per ml), Phenergan (6.25 mg per ml), and chlorpromazine (6.25 mg per ml) was given intramuscularly.…”

Section: Methodsmentioning

confidence: 99%

Myocardial Lactate and Pyruvate Metabolism*

Krasnow¹,

Neill²,

Messer³

et al. 1962

J. Clin. Invest.

128

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Although the heart has been considered primarily an aerobic organ, recent work (1) has reemphasized the possibility that measurement of oxygen consumption alone may not 1)e adequate to define the total energy utilization under all conditions. The role of anaerobic metabolism must be reviewed.Methods of defining as well as quantifying anaerobiosis are currently in dispute. When oxidation and glycolysis proceed at the same rate, carbohydrate is oxidized to CO2 and H20. Lactate arises whenever the rate of glycolysis exceeds the rate of oxidation. Net production of lactate by an organ, as evidenced for example by venous concentration greater than arterial, has been considered to represent anaerobic metabolism due to cellular hypoxia (2). More recent work (3) has demonstrated that large changes in lactate production can occur unassociated with hypoxia, but related instead to increased pyruvate production. Huckabee introduced the concept of "excess lactate" in order to distinguish between pyruvateinduced changes in lactate and those related solely to a shift in DPN: DPNH redox potential. This was inferred from alterations in arterial lactatepyruvate ratio and the relative arteriovenous differences of the two substrates. "Excess lactate," so defined, was considered an indicator of cellular oxygenation and was used quantitatively as a measure of anaerobic metabolic rate.Anaerobic metabolism in cardiac muscle has been considered to occur only under extreme conditions. Whereas earlier work (4-9) showed lactate production only sporadically with stresses of hypoxia, shock, or myocardial emboli, Huckabee (1) found that in dogs the stress of either 10 per cent oxygen breathing or leg exercise would result in myocardial excess lactate despite positive

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“…Digoxin;i augnientava (1) le intonsitate del utilisation de glucosa per lc myocardio (50 pro cento), (2) le contribution do glucossi ill inctiibolisiuo totnl del myocardio (ab 8 a 23 pro cento), (3) le iutensitatc del production de bioxydo do carbon a C" (250 pro cento), o (4) le intensitiito del transition del metabolites intcrinodiari in le vins glycolytic e respiratori. Iste altoratioiies oecurrova in le absentia, do alterntiones significative in lo functioiics dynamic del myocardio.…”

Section: Summario In Interlinguaunclassified

“…Studies of the changes in the substrate utilization of the heart in congestive failure 2 and after treatment with a cardiac glycoside 3 have indicated a lack of significant alteration in the metabolic activity of the myocardium. There have been no direct studies of the intermediary metabolism of the heart to substantiate these findings.…”

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confidence: 99%

The Effect of Digoxin on the Intermediary Metabolism of the Heart as Measured by Glucose-C ¹⁴ Utilization in the Intact Dog

Kien

Sherrod

1960

Circulation Research

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Adniinistrntion of a therapeutic close level of digoxin in the intact clog resulted in an augmentation of the glucose utilization of the myocardium accompanied by a. greatly increased rate of glycolytic and oxidative activity. The contribution of glucose to the total metabolism of the heart was increased, and the utilization of noncarbohydrate substrates was decreased. These metabolic changes occurred in the absence of changes in the dynamic functions of the heart, indicating that the metabolic alterations were due to a primary effect of the drug rather than an effect secondary to an altered state of cardiac activity.A /ITIOUGH great advances have been made in the basic biochemical and physiological mechanisms of cardiac contractility 1 there still remains a general lack of agreement concerning the mechanism of action of the cardiac glycosides. A further knowledge of the mechanism of action of digitalis in returning the failing heart to a state of compensation would facilitate an understanding of the metabolism of the normal myocardium and the pathogenesis of cardiac failure.Studies of the changes in the substrate utilization of the heart in congestive failure 2 and after treatment with a cardiac glycoside 3 have indicated a lack of significant alteration in the metabolic activity of the myocardium. There have been no direct studies of the intermediary metabolism of the heart to substantiate these findings. Based on the utilization of C" labeled substrates by clog ventricle strips, Wollenberger 4 suggested an action of ouabaiu on metabolic processes.The following experiments were specifically designed to correlate the cardiac hemodynamic action of digoxin with possible alterations in the dynamics of the intermediary metabolic pathways involved in the myocardial utilization of glucose-C 14 in the normal dog. Methods Cardiovascular Effects of DigoxinThe cardiovascular effects of 0.065 mg./Kg\ digoxin, administered rapidly as a, single intravenous dose, wore determined in young male dogs weighing-10 to 16 Kg. The animals were anesthetized by the intravenous administration of pentobarbital sodium (25 to 35 nig./Kg.) to the point of loss of the lid reflex but presence of a cornea 1 reflex. The trachea was cannulated and the animal was allowed to breathe room air which was supplemented with oxygen via a tracheal catheter in order to insure an arterial blood oxygen content of not less than 19 volumes per cent. The carotid artery was cannulated, and a polyethylene catheter was placed in the aorta for measurement of blood pressure by means of a, Statham transducer. Venous pressure was similarly measured by means of a catheter inserted via the jugular vein and positioned at the bifurcation of the inferior and superior vena, cavae. Left ventricular pressure was obtained via a fine polyethylene catheter inserted into the left ventricular chamber by way of the carotid artery and aorta. Cardiac output, coronary blood flow (in the circumflex branch of the left coronary artery), cardiac work, cardiac arterio-venous oxygen differ...

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Studies on Myocardial Metabolism. V. The Effects of Lanatoside-C on the Metabolism of the Human Heart 1

Cited by 42 publications

References 20 publications

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

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

Myocardial Lactate and Pyruvate Metabolism*

The Effect of Digoxin on the Intermediary Metabolism of the Heart as Measured by Glucose-C ¹⁴ Utilization in the Intact Dog

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Studies on Myocardial Metabolism. V. The Effects of Lanatoside-C on the Metabolism of the Human Heart 1

Cited by 42 publications

References 20 publications

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

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

Myocardial Lactate and Pyruvate Metabolism*

The Effect of Digoxin on the Intermediary Metabolism of the Heart as Measured by Glucose-C 14 Utilization in the Intact Dog

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The Effect of Digoxin on the Intermediary Metabolism of the Heart as Measured by Glucose-C ¹⁴ Utilization in the Intact Dog