Mg Of Digoxin Research Articles

Effect of multiple doses of losartan on the pharmacokinetics of single doses of digoxin in healthy volunteers.

1. Losartan (DuP 753, MK-954) is a novel, potent and highly selective AT1 angiotensin II receptor antagonist. The effect of multiple oral doses of losartan on digoxin pharmacokinetics was evaluated in healthy male subjects. 2. In a double-blind and randomized fashion, subjects received 50 mg losartan or placebo once daily for 15 days in each period. At least 7 days elapsed between the two treatment periods. On days 4 and 11 of each period, subjects also received a single 0.5 mg dose of digoxin intravenously and orally respectively. 3. Eleven of 13 subjects completed the study. Side effects were mild and transient (12 out of 13 subjects reported at least one adverse experience). During the study, no laboratory abnormalities were noted. 4. Multiple oral doses of losartan (50 mg daily) did not affect the pharmacokinetic parameters of 0.5 mg of digoxin i.v. AUC(0.48h) of immunoreactive digoxin during losartan 28.8 +/- 2.9 vs 28.5 +/- 3.9 ng ml-1 h during placebo; not significant, and 96 h urinary excretion [% dose] during losartan 54.0 +/- 7.2 vs 51.9 +/- 6.5% during placebo; not significant). Geometric mean ratios (90% confidence interval) for AUC and urinary excretion were respectively, 1.03 (0.98, 1.08) and 1.09 (0.98, 1.21). 5. Multiple oral doses of losartan did not affect the pharmacokinetic parameters of oral digoxin AUC(0.48 h) during losartan 23.6 +/- 3.7 ng ml-1 h vs 22.4 +/- 2.6 ng ml-1 h during placebo; not significant, Cmax 3.5 +/- 0.7 ng ml-1 with vs 3.1 +/- 0.5 ng ml-1 without losartan; not significant and tmax 0.6 +/- 0.2 h with vs 0.9 +/- 0.7 h without losartan; not significant, and 96 h urinary excretion [% dose] during losartan 51.2 +/- 6.3 vs 46.3 +/- 2.4% during placebo; not significant). Geometric mean ratios (90% confidence interval) for AUC and urinary excretion were respectively, 1.06 (0.98, 1.14) and 1.12 (0.97, 1.28). 6. We conclude that multiple oral doses of losartan (50 mg daily) do not alter the pharmacokinetics of immunoreactive digoxin, following either intravenous or oral digoxin. Furthermore, the co-administration of digoxin with losartan is well tolerated by healthy male volunteers.

A comparison of captopril and digoxin in the treatment of patients with mild-to-moderate chronic congestive heart failure

In a double-blind study, 116 patients (mean age, 57.6 years) with mild-to-moderate chronic congestive heart failure who were in sinus rhythm were randomly assigned to receive 25 mg of captopril were daily (up to 50 mg twice daily, if needed) plus hydrochlorothiazide (HCTZ) (group 1) or 0.1 mg of digoxin twice daily plus HCTZ (group 2) for 12 months. During a 3-to 4-week pretreatment stabilization period, group 1 received a mean of 37.7 mg of HCTZ daily and group 2 received 34.9 mg daily. After 6 weeks and 12 months of treatment, improvement was noted in both treatment groups on five measures of cardiac function: exercise tolerance, left ventricular end-diastolic diameter (LVEDD), ejection fraction, blood pressure, and heart rate. At 12 months, significantly greater improvement was noted in group 1 than in group 2 in exercise tolerance (from 329 seconds at baseline to 445 seconds at 12 months in group 1 and from 353 to 427 seconds in group 2; P < 0.05); LVEDD (from 60.5 to 56.5 mm in group 1 and from 60.3 to 57.9 mm in group 2; P < 0.05); and blood pressure (from 103.5 to 95.6 mm Hg in group 1 and from 101.9 to 97.0 mm Hg in group 2; P < 0.03). Clinical severity (New York Heart Association class) improved in both groups; 52% of the patients in group 1 and 41% in group 2 dropped an average of one functional class ( P < 0.01). The results indicate that captopril combined with a diuretic is an effective initial treatment for patients with mild-to-moderate congestive heart failure.

Electrophysiologic findings in Fabry's disease with a short PR interval

Fabry’s disease is an X-linked lysosomal storage disease caused by a deficiency of a-galactosidase-A that results in an accumulation of intracellular glycolipid in the heart and other organs. l Several electrocardiographic changes have been described in affected patients, including varying degrees of atrioventricular block, ST and T-wave changes, and a short PR interval.24 These changes are thought to be due to glycosphingolipid deposition involving the myocardial fibers and conduction system.24 However, the etiology of a short PR interval in Fabry’s disease is not completely understood. We report a patient with heterozygous Fabry’s disease who presented with palpitations and a short PR interval, and underwent detailed electrophysiologic testing. A 43-year-old white woman with a well-documented history of a carrier state for Fabry’s disease (based on decreased levels of a-galactosidase)presented with palpitations and dyspnea. On examination, her pulse was irregular, with a rate of 150 beats1 min. An initial electrocardiogram demonstrated atrialBbrillation, with an average ventricular response of approximately 150 beatslmin and shortest RR interval of 350 ms. A total of 0.75 mg of digoxin was administered in sequential doses, followed by conversion to normal sinus rhythm. Further digoxin dosing was held. An electrocardiogram recorded during sinus rhythm (Figure 1) showed a short PR interval of 110 ms, with a normal QRS duration and no evidence of preexcitation. The echocardiogram was normal. To assess the etiology of the short PR interval, an electrophysiologic

Ventricular Fibrillation Following Adenosine Administration

An 86-year-old woman was treated for atrial fibrillation. A total of 1.00 mg of digoxin and 12.5 mg of verapamil hydrochloride were administered intravenously during an 8-hour period with no slowing of her heart rate, but the rhythm became regular. Subsequently, 15 mg of verapamil hydrochloride was administered intravenously during a 40-minute period with no reduction in heart rate. Adenosine (6 mg) was then administered intravenously. Approximately 20 seconds after adenosine infusion into a vein in the patient's right arm, a 2.2-second pause developed, followed by ventricular flutter and then fibrillation. The patient required resuscitation and defibrillation.

Effect of digoxin on the heart in normal subjects: influence of isometric exercise and autonomic blockade: a noninvasive study.

1. Eight healthy subjects were studied before digoxin and after successive therapy periods of 1 week 0.125, 0.25 and 0.50 mg of digoxin. The mean serum concentrations (+/- s. d.) were 0.4 +/- 0.2, 0.6 +/- 0.3 and 1.4 +/- 0.5 nmol l-1, respectively. The effects of digitalis were studied by echocardiography and systolic time intervals at rest and after 3 min handgrip exercise. Effects of simultaneous autonomic blockade induced by atropine and propranolol were also examined. 2. Digoxin in increasing doses slowed the heart rate at rest; with the daily dose of 0.50 mg from 63 +/- 10 to 53 +/- 6 beats min-1, and fractional shortening rose from 28 +/- 6 to 33 +/- 3% (P less than 0.05 for both). Preload, afterload and cardiac output did not change. The electromechanic systolic time index (QS2I) decreased (P less than 0.001) and the observed alteration of QS2I was dose-related. 3. The influence of digoxin was similar during isometric exercise, except for unchanged fractional shortening. 4. During autonomic blockade digoxin slowed the intrinsic heart rate from 93 +/- 6 to 86 +/- 6 beats min-1 (0.25 mg) and to 83 +/- 6 beats min-1 (0.50 mg) (P less than 0.01 for both). QS2I was shortened (P less than 0.01). Echocardiographically determined ejection phase indices remained unchanged. 5. When handgrip stress was induced during autonomic blockade, digoxin evoked a clearcut increase in contractile function, resembling the effects of digoxin alone at rest. Thus, fractional shortening increased by 14% and QS2I decreased by 16 ms (P less than 0.01 for both). 6. We conclude that digoxin increases the contractility in normal heart without changes in loading conditions. The rise in inotropy at rest is obvious from both fractional shortening by echo and systolic time intervals. The same takes place during handgrip with autonomic blockade, when the heart lacks sympathetic support. The influence of long-term digoxin on heart rate is partly direct without autonomic mediation. The effect of digoxin is dose-dependent.

The effect of dietary fiber on the bioavailability of digoxin in capsules.

Sixteen healthy volunteers were regularly given 0.4 mg of digoxin daily as two capsules with breakfast. After ten days during which breakfast was supplemented with 11 g of bran fiber, steady-state predose mean serum digoxin was lower (0.89 +/- 0.19 versus 0.84 +/- 0.18 ng/mL, P less than .05) and mean 24-hour area under curve determination was lower (30.5 +/- 6.1 versus 28.4 +/- 6.0 ng X hr/mL, P less than .05) than during the control period without bran. Height and time of peak serum digoxin, and 24-hour urinary digoxin were not significantly different. The 6 to 7% reduction in digoxin absorption from capsules is less than that reported from tablets and is probably clinically unimportant.

No increase in serum digoxin concentration with high-dose diltiazem

The effect of incremental diltiazem dosing during concomitant digoxin administration over a four-week period in eight healthy adult volunteers (mean age, 28 ± 4 years) was studied. The study group received 0.25 mg of digoxin twice daily for two days, after which they received 0.25 mg daily for the duration of the study. Following baseline electrocardiographic evaluation and measurement of trough digoxin levels, all subjects received 120 mg of diltiazem daily for one week, then 240 mg daily for one week, followed by 360 mg daily for one week. Resting electrocardiographic parameters (heart rate, P-R interval), renal function, electrolyte values, and digoxin and diltiazem concentrations were measured weekly. Daily administration of 360 mg of diltiazem plus 0.25 mg of digoxin resulted in a significant decrease in heart rate (from 68 ± 9 beats per minute to 61 ± 10 beats per minute; p <0.05), a marginal increase in P-R interval (from 169 ± 22 msec to 179 ± 21 msec; p = 0.08), and no significant change in trough serum digoxin concentration (from 0.85 ± 0.08 ng/ml to 0.90 ± 0.08 ng/ml; p = NS). The administration of up to 360 mg of diltiazem per day with 0.25 mg of digoxin per day was not associated with significant increases in serum digoxin concentrations in healthy subjects.

Inhibitory effect of acute and chronic administration of digitalis on the sick sinus node.

We have determined the effects of the acute administration of intravenous (i.v.) digitalis administration (0.8 mg of digoxin in 5-10 min) on the electrophysiological variables of 12 normal subjects (group 1), 12 patients with asymptomatic sinus node bradycardia (group 2) and 34 patients with symptomatic sinus node dysfunction (SSS) (group 3). The injection of digitalis induced: an increase of sinus node cycle length (SNCL) in all groups; a 10% increase of sinus node recovery time (SNRT) in group 1, no changes in group 2 and a 25% increase in group 3; a tendency to increase, without reaching statistical significance, of corrected sinus node recovery time (CSNRT) and sino-atrial conduction time (SACT) in all groups. In 16 patients of group 3 the effects of oral chronic treatment with digoxin (0.25 mg daily for 7 days) was also determined. The results show that chronic treatment did not further affect SNCL, SNRT or CSNRT, but caused a greater increase of SACT than did the acute i.v. administration. Chronic treatment significantly reduced the sinus rate and increased the number of premature supraventricular and ventricular beats, measured by means of 24 hour-Holter monitoring. These data suggest that digitalis should be used with great caution in patients with SSS.

Acute effects of digoxin on total systemic vascular resistance in congestive heart failure due to dilated cardiomyopathy: A hemodynamic-hormonal study

The effects of the digitalis glycosides on systemic vascular resistance (SVR) in patients with congestive heart failure (CHF) are controversial. Most investigators report a reduction in total SVR, an action that has been attributed primarily to withdrawal of elevated sympathetic tone. Direct proof of this hypothesis is lacking, however, and the roles played by the renin-angiotensin-aldosterone and vasopressin systems have not been fully explored. Moreover, in several studies of patients with CHF, SVR did not decrease after the administration of digitalis. To clarify these issues, the hemodynamic and hormonal effects of digoxin were correlated in 11 normotensive men in sinus rhythm with CHF due to dilated cardiomyopathy. Patients were evaluated at rest and during submaximal exercise before and 6 hours after the intravenous infusion of 1.0 mg of digoxin (mean serum concentration 1.7 ng/ml). With digoxin therapy, heart rate, pulmonary wedge pressure and right atrial pressure declined and cardiac output increased. Although vasopressin was unchanged, both plasma norepinephrine concentrations and plasma renin activity decreased, the reduction in norepinephrine correlating with the increase in cardiac output. Despite these hemodynamic and hormonal effects, there was no change in total SVR at rest or during exercise. It is concluded that the improvement in cardiac function with digoxin in this patient group was a result of the inotropic properties of the drug, without an associated reduction in impedance. The failure of total SVR to decrease despite decreases in plasma norepinephrine levels and plasma renin activity might be explained by concomitant digitalis-induced vasoconstriction, impaired ability of arterioles to dilate in CHF, or offsetting alterations in other vasoactive hormone systems.

Wolff-Parkinson-White Syndrome

Mary Sears, MD, Resident in Medicine, Jewish Hospital at Washington University, St Louis: A 22-year-old man came to the emergency room of another hospital complain ing of light-headedness and palpitation of several hours' duration, the onset of which had occurred while he was swimming in a lake. On initial examination his systolic BP was 80 mm Hg and his apical rate was too rapid to count. A 12-lead ECG of poor technical quality showed a grossly irregular rhythm without distinguishable organized atrial activity. The ventricular rate averaged 285 beats per minute, and the width of the QRS complex varied from 80 to 120 ms. Deep Q waves were present in the inferior limb leads, and a tall, primordial R wave was noted in the anterior chest leads V 2 and V 3 . The patient initially received 1 mg of digoxin in two divided doses intravenously (IV), followed by 6 mg

Interaction of flecainide with digoxin and propranolol

The effect of flecainide, 200 mg twice daily for 5 days, on steady-state plasma digoxin levels was determined in 15 healthy male subjects who received 0.25 mg of digoxin per day. The predose mean plasma digoxin level before flecainide administration on days 9 and 10 was 0.46 ng/ml, compared with 0.57 ng/ml on day 13 (p < 0.05) and 0.49 ng/ml on day 15 (difference not significant [NS]) when flecainide was given concurrently with digoxin. The 6-hour postdose mean level for days 9 and 10 was 0.58 ng/ml, compared with mean levels of 0.62 ng/ml on day 13 (NS) and 0.65 ng/ml on day 15 (p < 0.05). On average, predose and 6-hour postdose digoxin levels increased by 24 ± 35% and 13 ± 19%, respectively, during co-administration. A significant prolongation of the electrocardipgraphic PR interval in 6 of 15 subjects was noted on the combined drug dosage. This reverted to normal after cessation of drug administration. Vital signs showed no significant clinical change during the course of the study. Ten other healthy male subjects were given propranolol, 80 mg 3 times daily, or flecainide, 200 mg twice daily, alone or in combination. Effects on vital signs, exercise heart rate, electrocardiographic interval, M-mode indexes of ventricular function and plasma drug levels were monitored to determine effects of the study drugs when given separately or concurrently. Both drugs caused a decrease in blood pressure, with the systolic pressure affected more than the diastolic; the effects of propranolol and flecainide were additive. Propranolol markedly decreased the pulse rate; flecainide increased the pulse rate slightly; concomitant effects were additive. The electrocardiographic PR interval was prolonged by both drugs; concomitant administration gave a subadditive effect. Echocardiographic changes were consistent with a negative inotropic effect, with propranolol more active than flecainide; concomitant effects were additive. Average plasma drug levels (AUC values) for both propranolol and flecainide were elevated somewhat (≤ 30%) by concurrent administration; the increases were not associated with any synergistic cardiodynamic effects. Plasma half-life was not altered for either drug by co-administration.

Hemodynamic effects of combined digoxin and dopamine administration in postoperative patients with cardiac dysfunction

In 10 patients with postoperative cardiac dysfunction which required dopamine for inotropic and hemodynamic support, we observed the cardiovascular effects of short-term digoxin administration. The average dosage of dopamine was 7.45 μg/kg per minute and was maintained while the patients were given 1 mg of digoxin over 8 hours. The dosage of dopamine was then tapered over the next 4 hours. We observed a significant increase in the cardiac index (4 hours) and a reduction in the heart rate (8 hours) before the dopamine dosage was reduced. After a reduction in dopamine dosage to 2.28 μg/kg per minute, these effects persisted. No significant changes were noted in systemic vascular resistance or pulmonary artery diastolic pressure during digoxin administration. These results indicate that the inotropic effects of dopamine and digoxin are additive when given in combination and that digoxin can be used to significantly reduce the dopamine dosage in patients with postoperative cardiac failure. Thus, the combination of an acute inotropic agent, dopamine, and a chronic inotropic agent, digoxin, appears to be clinically useful in postoperative cardiac dysfunction.

Clinical course of acute atrial fibrillation treated with rapid digitalization

Forty-seven episodes of acute atrial fibrillation (AF) in 45 patients were examined prospectively to determine the course of the disorder treated with rapid digitalization. Patients received 1.5 mg of digoxin intravenously over 12 hours. In 40 of the 47 attacks, reversion to sinus rhythm occurred with no additional therapy at 1 to 96 hours (median 4 hours) after beginning digoxin. In thirty-two patients, conversion occurred within 8 hours; only one patient showed important ventricular slowing before conversion. Thus, if digoxin facilitates conversion, it does not do so by slowing the ventricular response. Of the 11 patients still in AF at 16 hours, conversion subsequently occurred in only four who were receiving digoxin alone. We conclude that the prognosis for quick reversion to sinus rhythm in patients with acute AF treated with rapid digitalization alone is excellent. If reversion does not occur by 16 to 24 hours, additional measures to restore sinus rhythm are indicated.

Massive Reversible Prerenal Azotemia

To the Editor. —We saw a patient with transient excessively high urea levels presumably resulting from starvation and dehydration. Report of a Case. —A 68-year-old hypertensive man was seen initially in July 1980 with severe pulmonary edema in association with acute myocardial infarction. The patient's hospital course was normal, except for moderate renal failure (ie, a serum urea level of 73 mg/dL, a serum creatinine level of 2.4 mg/dL, and a serum creatinine clearance of 40 mL/min). He was discharged from the hospital in satisfactory condition on a combined regimen of 0.25 mg of digoxin five times per week, 40 mg of oral furosemide every other day, and 750 mg of methyldopa per day. Three weeks later, the patient was readmitted to the hospital because of dramatic deterioration of his condition, with vomiting and confusion. The patient recalled that, shortly after being discharged, he had separated from his female companion

Digoxin bioavailability during quinidine administration.

Digoxin serum concentration rises in the presence of quinidine. To determine whether quinidine alters digoxin bioavailability, six subjects received 1.0 mg of digoxin intravenously alone and by mouth on alternate weeks during steady-state oral quinidine administration. The area under the digoxin concentration:time curves (AUC) and the amount of digoxin excreted in the urine (Xxu) were determined for the 96 hr after each of the four experiments. Values for digoxin bioavailability relative to the corresponding intravenous study in the absence and presence of quinidine were (+/- S.D.) 73.5 +/- 8.6% and 79.5 +/- 22.6% (P greater than 0.05) for serum and 69.8 +/- 6.8% and 70.2 +/- 10.5% (P greater than 0.05) for urine. There was no difference in the steady-state quinidine serum concentration during the 4 days after intravenous and oral digoxin. We conclude that quinidine does not alter digoxin bioavailability and therefore that altered absorption does not explain the rise in digoxin serum concentration in the presence of quinidine.

Evidence of nonlinearity in digoxin pharmacokinetics.

Six normal male volunteers received 0.5 mg label doses of digoxin as (a) a bolus intravenous injection over 2 min, (b) a constant rate intravenous infusion over 1 hr, (c) a constant rate intravenous infusion over 3 h, and (d) a solution in 5% dextrose given orally. Plasma concentrations of digoxin were measured by radioimmunoassay for a 4 day period and urinary excretion for a 6 day period after the single doses. The mean (coefficient of variation) total areas under the plasma concentration-time curves per 0.5 mg of digoxin were (a) 35.55 (14.8%), (b) 30.20 (27.7%), (c) 25.80 (35.5%), and (d) 15.47 (49.9%); the means differed significantly (0.01 greater than p greater than 0.005). The mean (coefficient of variation) total amounts excreted in the urine as a fraction of the dose were (a) 0.689 (6.31%), (b) 0.517 (20.4%), (c) 0.588 (16.8%), and (d) 0.374 (23.4%); the means differed significantly (p less than 0.001). Both the total clearance and the nonrenal clearance of digoxin differed significantly with the method of intravenous administration. The slower the rate of input of digoxin to the body, the greater were both the total clearance and the nonrenal clearance of the drug, which strongly suggests nonlinear pharmacokinetics.

Combined therapy with digoxin and nitroprusside in heart failure complicating acute myocardial infarction

The hemodynamic effects of digoxin plus nitroprusside were compared with those of nitroprusside alone in 11 patients with congestive heart failure complicating acute myocardlal infarction. Hemodynamic measurements were made using a Swan-Ganz thermodilution catheter and a bedside thermodilution cardiac output computer. Patients received increasing doses of nitroprusside until mean arterial pressure decreased to 70 mm Hg or pulmonary arterial wedge pressure decreased to 16 mm Hg. The infusion rate of nitroprusside was then held constant for 120 minutes. After 30 minutes of constant nitroprusside infusion, 0.5 mg of digoxin was given intravenously. Hemodynamic measurements were obtained before treatment with nitroprusside and immediately before and 30, 60 and 90 minutes after the administration of digoxin. Nitroprusside produced a significant decrease in pulmonary arterial wedge pressure (24 to 16 mm Hg), mean arterial pressure (92 to 85 mm Hg and systemic vascular resistance (1,816 to 1,480 dynes sec cm −5) and a significant increase in cardiac index (2.19 to 2.51 liters/min per m 2). Ninety minutes after the administration of digoxin, cardiac index was further increased (2.51 to 28.2 liters/min per m 2, P = 0.03) and systemic vascular resistance was tower (1,480 to 1,320 dynes sec cm −5, P = 0.03). Pulmonary arterial wedge pressure was not further decreased by the addition of digoxin. Thus, the addition of digoxin further increases cardiac output in patients with congestive heart failure complicating myocardial infarction who are receiving nitroprusside but does not produce any further decrease in pulmonary arterial wedge pressure.

Quinidine-digoxin interaction

<h3>To the Editor.—</h3> We read the report by Leahey et al (240:533,1978) of a possible interference with serum digoxin concentrations by quinidine. Indeed, we as well as others have made similar observations.¹However, based on the data presented, we have some reservations regarding the incidence of this interaction. Many of the serum digoxin concentrations reported as steady-state values before quinidine therapy were considerably lower than would have been expected based on the dose of digoxin supposedly being administered. We estimated the steady-state serum digoxin concentrations for hypothetical patients with creatinine clearances of 50, 75, and 100 mL/min to be 1.9, 1.5, and 1.2 ng/mL, respectively.²(To make these calculations, we assumed a lean body weight of 70 kg and daily administration of 0.25 mg of digoxin with 80% absorption.) Since these calculated serum digoxin concentration values are considerably higher than many of those reported by the authors, we question

Quinidine-Digoxin Interaction

To the Editor.— We read the report by Leahey et al (240:533,1978) of a possible interference with serum digoxin concentrations by quinidine. Indeed, we as well as others have made similar observations. 1 However, based on the data presented, we have some reservations regarding the incidence of this interaction. Many of the serum digoxin concentrations reported as steady-state values before quinidine therapy were considerably lower than would have been expected based on the dose of digoxin supposedly being administered. We estimated the steady-state serum digoxin concentrations for hypothetical patients with creatinine clearances of 50, 75, and 100 mL/min to be 1.9, 1.5, and 1.2 ng/mL, respectively. 2 (To make these calculations, we assumed a lean body weight of 70 kg and daily administration of 0.25 mg of digoxin with 80% absorption.) Since these calculated serum digoxin concentration values are considerably higher than many of those reported by the authors, we question

Effect of digoxin on coronary blood flow and myocardial oxygen consumption in patients with chronic coronary artery disease

In 10 patients with chronic coronary artery disease and without clinical evidence of congestive heart failure, the effects of 1.0 mg of digoxin intravenously on systemic hemodynamics, coronary blood flow, myocardial oxygen consumption and myocardial lactate extraction were studied both at rest and during atrial pacing. Atrial stimulation at a rate just below the threshold for angina led to a significant decrease in left ventricular enddiastolic pressure, from 10.6 ± 1.6 to 7.1 ± 0.8 mm Hg, associated with a significant decrease in left ventricular stroke work index per beat, from 76.7 ± 5.11 to 40.3 ± 4.01 g-m/m 2. After digoxin, nearly identical results in stroke work index could be observed at rest and during stimulation (75.2 ± 6.74 and 44.1 ± 5.92, respectively). However, left ventricular enddiastolic pressure decreased significantly before and during atrial stimulation (8.1 ± 1.29 and 4.7 ± 1.09 mm Hg, respectively). Cardiac index decreased from 3.08 ± 0.20 to 2.73 ±0.17 liters/min per m 2 at rest but during pacing it no longer differed before and after digoxin (3.17 ± 0.22 and 3.10 ± 0.20 liters/min per m 2, respectively). Myocardial oxygen consumption and lactate extraction remained unchanged after digoxin both at rest and during atrial pacing. It is concluded that some deficiency in left ventricular function is present in patients with chronic coronary artery disease even without clinical evidence of congestive heart failure. Digoxin improves left ventricular performance at rest and during stress conditions. An expected increase in myocardial oxygen consumption due to enhanced contractility is completely counterbalanced, probably by a decrease in left ventricular volume after digoxin.