The effect of deslanoside on the duration of the phases of ventricular systole in man

Weissler, Arnold M.; Kamen, Alan R.; Bornstein, Richard S.; Schoenfeld, Clyde D.; Cohen, Sidney

doi:10.1016/0002-9149(65)90449-2

Cited by 86 publications

(23 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar results were obtained by Das et al (1977), although the method for correcting STI for variations in heart rate was not comparable. (Weissler et al, 1965;Lewis et al, 1974;Das et al, 1977). While the PEP in the present study certainly tended to shorten with a profile similar to that observed for the QS2 and LVET the analysis of variance failed to show that this represented a significant change over the placebo.…”

Section: Discussionsupporting

confidence: 62%

Haemodynamic effects of BM 10.188, a new orally active inotropic agent, in healthy volunteers.

Whiting¹,

Kelman²,

Sumner³

et al. 1982

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 62%

Haemodynamic effects of BM 10.188, a new orally active inotropic agent, in healthy volunteers.

Whiting¹,

Kelman²,

Sumner³

et al. 1982

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…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%

“…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: 65%

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.

View full text Add to dashboard Cite

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...

show abstract

“…The responses to digoxin are variable, small, and do not show a dose-response relationship. These fmdings are in contrast to several studies examining the response of left ventricular function to digoxin therapy in adults (21)(22)(23). Although differences in the physiologic response to digoxin may reflect developmental changes in the interaction of digoxin with its membrane receptor (24), there is little evidence to substantiate age-related differences in the binding to, dissociation from or inhibiting effect of digoxin on the myocardial Na-K ATP-ase system (25)(26)(27)(28)(29).…”

Section: Statisticsmentioning

confidence: 58%

The Effects of Ouabain in Lambs with Depressed Myocardial Function

1982

View full text Add to dashboard Cite

SummaryThe effects of ouabain infusion were tested in six lambs before and after depression of myocardial function by halothane anesthesia. Halothane reduced the left ventricular rate of pressure rise (dp/dt), stroke work, and stroke volume; the ratio of preejection period to left ventricular ejection time rose. Heart rate and systemic vascular resistance did not change. Before halothane, ouabain infusion did not alter the hemodynamic variables measured. After myocardial depression, ouabain infusion returned dp/ dt, stroke work, stroke volume and the ratio of preejection period to left ventricular ejection time to control levels. Pacing studies showed a biphasic relationship between left ventricular dp/dt and heart rate. Maximal dp/dt occurred at a heart rate 42 beats/min higher than the resting rate.These studies suggest resting myocardial performance in the healthy, newborn lamb is at near maximal level.The tolerance to and physiologic effects of cardiac glycosides differ in newborn and adult sheep (1,2). Studies have shown that age-related variations in the pharmacokinetics, metabolism, protein binding or tissue penetration of digoxin do not explain the biologic differences documented (3-7). The differences in drug effect may relate to developmental variation in the effects of cardiac glycosides on the myocardial sodium-potassium ATP-ase (Na-K ATP-ase) system. Recently, however, evidence has accumulated that the resting level of myocardial function in healthy newborn lambs is much higher than that in mature sheep (8-10). The high resting level of heart rate and myocardial function in the normal, nonfailing neonatal lamb heart may make inotropic stimulation with cardiac glycosides difficult to document.We tested the effects of ouabain infusion on the hemodynamic function of newborn lambs. Drug effects were measured in undisturbed, chronically instrumented, awake animals; studies were repeated after myocardial depression by halothane anesthesia. We also studied the contribution of heart rate to resting myocardial function in newborn lambs by testing the effect of atrial pacing on the hemodynamic variables measured. MATERIALS A N D METHODS ANIMAL PREPARATIONStudies were performed on six lambs ranging in age from 5-26 days and in weight from 3.8-12.5 kg. Animals were prepared surgically using 0.5% halothane anesthesia, administered by face mask, and pentobarbital sedation (5 mg/kg, IV). Polyvinyl catheters (0.050 inches ID; 0.090 inches OD) were inserted into the right atrium via the jugular vein and into the descending abdominal aorta via the femoral artery. A #5 French Millar catheter tip mesh pouch, sewn to the skin. Animals were treated postoperatively with 50,000 units/kg/day of penicillin and 15 mg/kg/day of Kanamycin, given intramuscularly. Studies were performed 48 h or more after surgery. RESTING STUDIESBaseline measurements. Resting measurements of hemodynamic function were made while the lambs rested quietly, blindfolded in an open cage. Physiologic data were recorded on a Beckman R-611 direct writing ...

show abstract

The effect of deslanoside on the duration of the phases of ventricular systole in man

Cited by 86 publications

References 15 publications

Haemodynamic effects of BM 10.188, a new orally active inotropic agent, in healthy volunteers.

Haemodynamic effects of BM 10.188, a new orally active inotropic agent, in healthy volunteers.

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

The Effects of Ouabain in Lambs with Depressed Myocardial Function

Contact Info

Product

Resources

About