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PubMed1980

Serum digoxin concentrations in dogs before, during, and after concomitant treatment with phenobarbital.

Healthy dogs were treated once a day for 26 days with a liquid, oral dosage form of digoxin (0.022 mg/kg). From day 10 to 24 they were also given phenobarbital (12 mg/kg, sid, orally). Serum digoxin concentration was measured by a radioimmunoassay technique. Eight hours after the 2nd daily dose of digoxin had been administered, serum digoxin concentration was in the accepted therapeutic range. After 3 days of concomitant administration of digoxin and phenobarbital, serum digoxin concentration began to increase. Beginning on day 15 until day 24 (last day of combined digoxin and phenobarbital treatment), a significant (P less than 0.05) increase in serum digoxin concentrations occurred. Blood urea nitrogen values remained within the normal limits throughout the study. There was no significant (P greater than 0.05) difference between base-line heart rate and P-R intervals and the values recorded during the investigation.

Animals↗
PubMed1981

Effects of apparently nontoxic doses of digoxin on ventricular ectopy after direct-current electrical shocks in dogs.

To determine whether nontoxic doses of digoxin increase the risk of serious ventricular arrhythmias after d.c. cardioversion, studies were made of the effects of different doses of digoxin on the incidence and severity of ventricular arrhythmias after graded, external d.c. shocks in 14 closed-chest dogs. Electrocardiograms were recorded continuously for 20 min before and 10 min immediately after sequential QRS-synchronized shocks of 10, 100 and 150 joules. Ventricular premature beats were counted and their severity was graded. Digoxin (0.01--0.05 mg/kg) was then given i.v. to 12 dogs. Despite a wide range of serum digoxin concentrations (1.3--12.5 ng/ml), electrocardiographic signs of digitalis toxicity did not develop in any of these animals. The same sequence of d.c. shocks was repeated after 2 hr in nine dogs and after more than 24 hr in three dogs. Neither the total number of ventricular ectopic beats nor the arrhythmia grade postshock differed significantly before and after digoxin. Furthermore, more dogs developed ventricular ectopy at each energy level after control shocks than following shocks after digoxin administration. Two additional dogs were given repeated digoxin doses until electrocardiographic evidence of digitalis toxicity was apparent. Both developed sustained ventricular tachycardia after electrical shocks at all energy levels. Whereas overt digitalis toxicity predisposes to serious ventricular arrhythmias after d.c. shocks, we conclude that the risk of postshock ventricular ectopy is not increased by pretreatment with apparently nontoxic digoxin doses.

Animals↗
PubMed1980

[Routine serum digoxin determination on hospital admission (author's transl)].

The purpose of the present study was the collection of data concerning digitalis treatment of patients outside hospital. The investigation was carried out on 200 patients over 60 years of age, consecutively admitted to a 750-bed general hospital (35% ot a medical ward, 65% to other specialities). An ECG and serum creatinine and digoxin determinations were performed on the day of admission and a careful history taken of the drugs administered before admission. 30 patients reported the use of digoxin or other digitalis drugs, whilst another 48 patients reported taking cardiac drugs in general. The prevalence of digoxin levels exceeding 2 ng/ml was 11.5% in the group of patients known to have taken digitalis preparations, 18% among the 92 patients with positive serum digoxin levels and highest (30%) in the subgroup admitted due to cardiac failure. In patients with digoxin levels above 2 ng/ml the prevalence of elevated serum creatinine values (greater than 1.2 mg%) was markedly increased. Among patients with normal serum creatinine levels the mean age of patients with digoxin levels above 2 ng/ml was significantly higher than of those with digoxin levels below 2 ng/ml. A clear correlation between digoxin levels and ECG changes was not demonstrable; simultaneous administration of diuretics promotes the appearance of electrocardiographic signs of digitalis toxicity.

Aged↗
PubMed1995

Determination of free digoxin in sera of 8 patients with chronic cardiac insufficiency.

AIM: To establish a method for the determination of free digoxin in serum for clinical use and to study the relationship between the free and total digoxin concentrations in chronic cardiac insufficiency patients receiving digoxin with different renal function. METHODS: The ultrafiltration with fluorescence polarization immunoassay was used to determine the concentration of free digoxin. RESULTS: The concentrations of digoxin standards in serum were 0.96, 1.92, and 3.84 nmol.L-1. The relative standard deviation was < 7% for intra-day and < 6% for inter-day determinations. The average recovery was 99.95 +/- 2.18%. The ratio of free/total digoxin in chronic cardiac insufficiency patients with renal dysfunction was lower than that in patients with normal kidneys (63.5 +/- 4.7% vs 75.1 +/- 3.9%, P < 0.01). CONCLUSION: The present method is simple and reliable. In these patients there is an over-measurement for total digoxin concentration, suggesting the presence of elevated endogenous digoxin-like immunoreactive substances.

Aged↗
PubMed1976

Pharmacist's effect on digoxin usage and toxicity.

Digoxin usage and toxicity were compared in a prospective group of patients who were monitored by a pharmacist and a retrospective group for which there was no pharmacist consultation. For the prospective group, the pharmacist monitored patients and estimated the steady-state digoxin levels by the use of a nomographic method. Level greater than 2.2 ng/ml and concurrent ECG or physical signs of digoxin toxicity were communicated to the physician. For the retrospective group, digoxin levels were calculated based on data from the patients' charts. The 49 patients in the two study groups were categorized according to four levels of digoxin toxicity (ranging from "no evidence" to "probable"). The only characteristic that was significantly different between the two groups was the calculated creatinine clearance (lower for the retrospective group). The maintenance dose of digoxin and the incidence of digoxin toxicity were significantly lower in the prospective group. It is concluded that pharmacist intervention may have had an effect in reducing digoxin dosage and toxicity.

Adult↗
PubMed1995

Lack of interaction between pantoprazole and digoxin at therapeutic doses in man.

Substituted benzimidazole inhibitors of the gastric H+/K+ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs. On the other hand, changes in intragastric pH might alter the absorption of other drugs. The primary aim of the present study was to determine whether pantoprazole modifies the steady-state serum concentrations of orally administered digoxin. Secondary aims were the influence of digoxin on the pharmacokinetics of pantoprazole as well as safety and tolerability. Eighteen healthy volunteers received a single oral dose of pantoprazole (40 mg) and serum concentrations were determined. Three to 10 days later, subjects received in a single-blind, randomized, crossover fashion oral beta-acetyldigoxin (0.2 mg) twice daily and concomitant oral pantoprazole (40 mg) or placebo once daily for 5 days. Serum concentrations of pantoprazole and digoxin were determined on day 5. Primary characteristics for confirmative assessment of no interaction were AUC and Cmax of digoxin. Lack of interaction in the sense of equivalence was concluded for both digoxin (with and without pantoprazole) and pantoprazole (with and without digoxin) as the 90%-confidence intervals of the respective AUC- and Cmax-ratios were within the equivalence range of 0.8-1.25. Pantoprazole did not influence the characteristic ECG modifications (T-wave) caused by digoxin. Both drugs were well tolerated and no adverse events or clinically relevant alterations in vital signs or clinical laboratory parameters were observed during treatment. In conclusion, pantoprazole and digoxin may be administered concomitantly without the need for dose adjustment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Absence of a sertraline-mediated effect on digoxin pharmacokinetics and electrocardiographic findings.

UNLABELLED: The effects of oral administration of sertraline on the plasma concentration profile and renal clearance of digoxin were assessed in 20 healthy male subjects in a double-blind, randomized study. METHOD: All subjects first received digoxin 0.5 mg twice daily on Day 1, 0.25 mg twice daily on Day 2, and 0.25 mg daily thereafter. On Day 11, 10 subjects began concomitant sertraline administration with an initial dose of 50 mg/day that was titrated upward over 7 days to 200 mg/day, which was given over the remainder of the study period. The other 10 subjects received concomitant digoxin and placebo for 17 days beginning on Day 11. Trough plasma concentrations of digoxin were monitored daily beginning on Day 7. Blood samples and 24-hour urine collections were used to determine steady-state digoxin concentration and renal clearance before, during, and after sertraline coadministration. RESULTS: Sertraline had no effect on digoxin pharmacokinetics, except for a decrease in the time to reach the maximum plasma digoxin concentration (Tmax) compared with placebo (p = .0046), a finding thought to be of limited clinical significance. Side effects of mild-to-moderate severity were reported by 5 of 10 sertraline-treated subjects and by 6 of 10 placebo-treated subjects. CONCLUSION: The results of this study suggest that dosing adjustments of digoxin may not be necessary in patients receiving concomitant sertraline administration.

1-Naphthylamine↗
PubMed1979

Microencapsulated antibodies in radioimmunoassay--I. Determination of digoxin.

We describe the application of the microencapsulated-antibody technique to the radioimmunoassay of digoxin in serum. Droplets of emulsified rabbit antibody are microencapsulated in a semipermeable nylon membrane by an interfacial polymerization technique. The antibody microcapsules are incubated with 125I-labeled digoxin and unlabeled digoxin for 15 min at 37 degrees C, then free and bound digoxin are separated by centrifugation. Subtherapeutic, therapeutic, and toxic concentrations of digoxin in sera can be determined, with use of a standard curve prepared by use of known amounts of digoxin. With this technique we obtained an intra-laboratory correlation coefficient of 0.945 for 100 patients' sera and one of 0.940 for interlaboratory results for 21 sera (10 laboratories) when compared to a routine clinical laboratory radioimmunoassay for digoxin. Icterus, lipemia, hemoglobin, or disproteinemia had no effect on the analytical recovery of digoxin. The standard curve was linear to 6 microgram/L; the sensitivity was 0.25 microgram/L.

Antibodies↗
PubMed1996

Lack of interaction between pantoprazole and digoxin at therapeutic doses in man.

Substituted benzimidazole inhibitors of the gastric H+/K+ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs. On the other hand, changes in intragastric pH might alter the absorption of other drugs. The primary aim of the present study was to determine whether pantoprazole modifies the steady-state serum concentrations of orally administered digoxin. Secondary aims were the influence of digoxin on the pharmacokinetics of pantoprazole as well as safety and tolerability. Eighteen healthy volunteers received a single oral dose of pantoprazole (40 mg) and serum concentrations were determined. Three to 10 days later, subjects received in a single-blind, randomized, crossover fashion oral beta-acetyldigoxin (0.2 mg) twice daily and concomitant oral pantoprazole (40 mg) or placebo once daily for 5 days. Serum concentrations of pantoprazole and digoxin were determined on day 5. Primary characteristics for confirmative assessment of no interaction were AUC and Cmax of digoxin. Lack of interaction in the sense of equivalence was concluded for both digoxin (with and without pantoprazole) and pantoprazole (with and without digoxin) as the 90%-confidence intervals of the respective AUC- and Cmax-ratios were within the equivalence range of 0.8-1.25. Pantoprazole did not influence the characteristic ECG modifications (T-wave) caused by digoxin. Both drugs were well tolerated and no adverse events or clinically relevant alterations in vital signs or clinical laboratory parameters were observed during treatment. In conclusion, pantoprazole and digoxin may be administered concomitantly without the need for dose adjustment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Inhibition of Na,K-ATPase by oleandrin and oleandrigenin, and their detection by digoxin immunoassays.

Ingestion of oleander plant, containing the cardiac glycoside oleandrin, has been reported to induce fatal poisonings. Derivatives of oleandrin are structurally similar to digoxin. We investigated the cross-reactivities of oleandrin and its aglycone metabolite, oleandrigenin, in several commercially available digoxin immunoassays; assessed their ability to inhibit Na,K-ATPase catalytic activity; and measured their binding to proteins in serum. As assayed with ACS:180, Stratus, RIA, On-Line, and TDx digoxin assays, oleandrin at 100 micromol/L in digoxin-free serum gave apparent digoxin values of 0, 0.83, 2.24, 2.37, and 5.34 nmol/L, respectively, whereas oleandrigenin at that concentration gave results of 0, 0.52, 0.77, 4.94, and 1.40 nmol/L. Study of Na,K-ATPase inhibition showed IC50 values (micromol/L) of 0.22 for ouabain, 0.62 for oleandrin, 1.23 for oleandrigenin, and 2.69 for digoxin. At 25 degrees C, 96% of oleandrin and 48% of oleandrigenin were bound to serum proteins. Because detection of oleandrin and oleandrigenin by digoxin immunoassays is variable between assays as well as between congeners, assessment of cross-reactivity is warranted for each assay. The inhibition of Na,K-ATPase by oleandrin and oleandrigenin confirms that they likely exert their toxic effects through inhibition of sodium pump activity. In cases of digitalis-like poisoning with suspicion of oleander ingestion, a combination of digoxin immunoassays may be useful to effectively rule out the presence of oleander.

Blood Proteins↗
PubMed1997

Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy.

BACKGROUND: This prospective study was designed to determine whether diltiazem is superior to digoxin for the prophylaxis of supraventricular dysrhythmias (SVD) after pneumonectomy or extrapleural pneumonectomy (EPP) and to assess the influence of these drugs on perioperative cardiac function. METHODS: Seventy consecutive patients without previous SVD were randomly allocated immediately after pneumonectomy or EPP to receive diltiazem (n = 35) or digoxin (n = 35). Diltiazem-treated patients received a slow intravenous loading dose of 20 mg, followed by 10 mg intravenously every 4 hours for 24 to 36 hours, then 180 to 240 mg orally daily for 1 month. Digoxin-treated patients received a 1-mg intravenous loading in the first 24 to 36 hours, then 0.125 to 0.25 mg orally daily for 1 month. A concurrent prospective cohort of 40 patients without previous SVD, who did not participate in the study and underwent pneumonectomy or EPP without prophylaxis, served as a comparison group for SVD occurrence. Serial Doppler echocardiograms were performed to assess cardiac function and all patients were continuously monitored with Holter recorders for 3 days. Data were analyzed by intent-to-treat. RESULTS: In patients undergoing standard or intrapericardial pneumonectomy, diltiazem prevented the overall incidence of postoperative SVD when compared with digoxin, 0 of 21 patients versus 8 of 25 patients, respectively, p < 0.005. When EPP patients were included in the analysis, diltiazem decreased the incidence of all SVD from 11 of 35 patients (31%) to 5 of 35 patients (14%) when compared with digoxin, p = 0.09. Digoxin-treated patients had a similar incidence of all SVD (31%) as concurrent controls (11 of 40 patients [28%]). The two treated groups did not differ in right or left atrial size, left ventricular ejection fraction, or right heart pressure. When all patients were combined, those in whom SVD developed were significantly older (65 +/- 12 years versus 55 +/- 11 years, p = 0.004) and had a longer median hospital stay (9 versus 6 days, p = 0.03), when compared with those in whom SVD did not develop, respectively. The subset of patients undergoing EPP had a greater incidence of atrial fibrillation and electrocardiographic changes suggestive of postoperative pericarditis than all other pneumonectomy patients. CONCLUSIONS: Diltiazem was both safe and more effective than digoxin in reducing the overall incidence of SVD after standard or intrapericardial pneumonectomy. Digoxin therapy had no effect on the incidence of postoperative SVD and is not recommended for prophylaxis of SVD. Dysrhythmias after pneumonectomy or EPP occur in older patients and are associated with a greater length of hospital stay.

Aged↗
PubMed1997

Relationship between high serum digoxin levels and toxicity.

A retrospective study of 1,269 patients on digoxin was done to determine the relationship between serum digoxin levels of 3.0 ng/ml or higher and clinical toxicity. Of 1,269 patients, 58 (4.6%) had digoxin serum levels of 3.0 ng/ml or higher. Clinical evidence of digoxin toxicity was present in only 11 of these patients and premature blood sampling accounted for the high levels in 10 other nontoxic patients. None of the patients with clinical toxicity died. The other 37 patients tolerated the high digoxin levels without exhibiting toxic effect. Low cardiac output, concomitant use of other drugs, and impaired renal function increased the serum digoxin levels in patients with and without clinical toxicity. Appropriate therapeutic digoxin level monitoring and confirmatory laboratory-clinical relationship may have important influences on these results. Additional work on further definition of "toxic" digoxin levels needs to be performed.

Adult↗
PubMed1998

[Comparison of the effects of digoxin or enalapril in the treatment of heart failure due to mitral insufficiency].

BACKGROUND: There is not much evidence about the usefulness of digoxin or enalapril in the treatment of heart failure due to mitral insufficiency. AIM: To compare digoxin and enalapril in the treatment of heart failure due to mitral insufficiency. PATIENTS AND METHODS: Patients with mitral insufficiency, in sinus rhythm, with a heart failure grade II or III and with echocardiographic left ventricular dilatation were eligible for the study. They received sequentially, during 12 weeks each, digoxin 0.25 mg/day or enalapril in doses up to 20 mg/day, with a washout in-between period of 2 weeks. The order of the sequence was determined randomly. At the start and end of treatment, functional class according to NYHA and maximal exercise tolerance in the treadmill were assessed and a color Doppler echocardiogram was done to measure ventricular dimensions, function and degree of mitral insufficiency. RESULTS: Nine patients on enalapril and 12 on digoxin improved their functional capacity. Digoxin improved exercise time in 76 +/- 168 sec (p = 0.022), whereas this change was not significant with enalapril (38 +/- 158 sec; p = 0.2). With enalapril treatment, ventricular diastolic dimension decreased from 59.3 +/- 8.1 to 58 +/- 9.3 mm and the area of mitral insufficiency decreased from 8.1 +/- 3.5 to 6.6 +/- 3.1 cm2. Digoxin did not induce any significant echocardiographic change. CONCLUSIONS: In these patients, digoxin and enalapril improved functional class. Digoxin improved exercise time and enalapril reduced ventricular dimensions and mitral insufficiency.

Adult↗
PubMed1997

Comparative study of the effects of ouabain and digoxin on blood pressure of rats.

OBJECTIVE: To compare the effect of ouabain on the blood pressure of rats with that of digoxin to find the evidences of the relationship between endogenous ouabain (EO) and development of hypertension. METHODS: Sprague-Dawley rats, which were divided into 3 groups, were infused with ouabain (23 x 75 micrograms.kg-1/day, i.p.), digoxin (36 x 84 micrograms.kg-1/day, i.p.) and normal saline (NS) once a day respectively. Systolic blood pressure and body weight were recorded weekly. Five weeks later, rats of ouabain group were randomly assigned to three infusion subgroups: Oc group, continued with ouabain infusion; Od group, added digoxin (73 x 68 micrograms.kg-1/day, i.p.) and Os group, stopped administration of ouabain. Another week later, direct blood pressure was recorded in aorta. Systolic and diastolic cardiac function, plasma renin activity and aldosterone levels of all the rats were measured. RESULTS: After a latent period of one week, blood pressure of Ouabain group increased significantly [95.4 +/- 11.8 mmHg (1 mmHg = 0.133 kPa) at the beginning of the experiment vs 122.5 +/- 16.9 mmHg at the end of week 6, P < 0.05] with normal plasma renin activity and higher aldosterone (1.28 +/- 0.45 ng/ml vs 0.69 +/- 0.27 ng/ml, P < 0.05). The blood pressure decreased after either withdrawal of ouabain or addition of digoxin (116.3 +/- 14.4 mmHg vs 100 +/- 10.7 mmHg, P < 0.05; 123.9 +/- 13.9 vs 103.3 +/- 10.5 mmHg, P < 0.05, respectively). No difference of blood pressure was found between the digoxin and NS group. CONCLUSIONS: Our results suggested that EO might be one of the causes of the development of hypertension. Aldosterone might play some role in the mechanism of ouabain-induced hypertension. Digoxin can not induce hypertension. There is a great difference between the effect of ouabain and digoxin on the blood pressure. Moreover, digoxin can reverse the hypertension induced by ouabain.

Animals↗
PubMed1994

Population Pharmacokinetics of Digoxin in Duchenne Muscular Dystrophy (DMD) Patients.

Routine clinical pharmacokinetic data collected from Duchenne muscular dystrophy (DMD) patients receiving digoxin have been analyzed to evaluate the role of patients' characteristics for estimating dosing regimens. The data were analyzed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The pharmacokinetic model of digoxin was described using a one-compartment steady-state model. The effect of factors on digoxin clearance was investigated. NONMEM estimates indicate that digoxin clearance was influenced by the variables of body weight and combination with diuretics. The interindividual variability in digoxin clearance was modeled with proportional error with an estimated coefficient of variation of 25%, and the intraindividual variability in digoxin concentration was modeled with equal error with an estimated standard deviation of 0.0828 ng ml(minus sign1). In order to determine whether the population parameters obtained in this study were accurate, we administered digoxin according to individual dosage regimens in four DMD patients, using these values obtained by the Bayesian method. As a result, we found that mean prediction error, which indicates the deviation of prediction accuracy for digoxin concentration in plasma, was small, as were mean absolute prediction error and root mean squared error, showing the accuracy of this prediction method. The dosing method based on clearance values obtained by NONMEM analysis allowed the prediction of the steady-state concentration as a function of maintenance dose with acceptable error for therapeutic drug monitoring.

Journal Article↗
PubMed1998

Effect of Digoxin on Ventricular Remodeling and Responsiveness of beta-Adrenoceptors in Chronic Volume Overload.

BACKGROUND: Digoxin improves baroreflex function and reduces neurohumoral activation in severe heart failure, but it is uncertain how digoxin affects ventricular remodeling and progression to left ventricular dysfunction. In addition, the effect of digoxin in in vitro beta-adrenoceptor density and function, and contractile reserve in vivo is not well understood. METHODS AND RESULTS: To study this, we compared digoxin with placebo treatment in rats with chronic volume overload induced by aortocaval fistula and in sham-operated control animals. Left ventricular end-diastolic cavity dimensions (LVDd) and wall thickness were measured weekly by in vivo transthoracic echocardiography, and left ventricular mass (LVM) and percent fractional shortening (%FS) were calculated. Six weeks after fistula creation, simultaneous echocardiographic and invasive hemodynamic evaluation at rest and in response to incremental dobutamine (1-10 µg/kg/min intravenously) were measured. Myocardial plasma membrane beta-adrenoceptor density and maximal adenylate cyclase responses (V(max)) to isoproterenol, 5'-guanylylimi dodiphosphate, and forskolin were measured in vitro. Volume overload induced progressive increases in LVDd and LVM over the 6-week study period. Percent fractional shortening at rest, and the change in %FS in response to dobutamine stress were dramatically reduced 6 weeks after fistula creation. Although 6-week fistula animals had unchanged beta-adrenoceptor density (B(max)) and binding affinity (K(d)) as compared with controls, maximal adenylate cyclase responses to stimulation in vitro (V(max)) were markedly reduced. Digoxin treatment prevented this loss of responsiveness of adenylate cyclase but did not affect beta-adrenoceptor density or affinity in vitro. Digoxin had no effect on LVDd, LVM, %FS, or the response to dobutamine infusion in vivo. CONCLUSIONS: Although digoxin prevented beta-adrenoceptor desensitization and improved in vitro myocardial adenylate cyclase response, the cardiac response to adrenergic stimulation in vivo was not significantly improved. These results suggest that the role of beta-adrenoceptor desensitization in the progression from volume overload hypertrophy to left ventricular dysfunction and heart failure may be less important than previously thought. Furthermore, although digoxin treatment did produce modest hemodynamic benefits, it did not prevent progressive remodeling in this model.

Journal Article↗
PubMed1976

Effects of ischemia and reperfusion on myocardial uptake of tritiated digoxin.

The effect of coronary reperfusion on the uptake of cardiac glycosides by ischemic myocardium was studied in 17 open chested dogs undergoing anterior wall infarction produced by snaring confluent branches of the left coronary system. Epicardial electrograms delineated ischemic zones of S-T elevation, border, and nonischemic zones. Animals were reperfused by snare release 1, 2, and 6 hr after occlusion. After 15 min of reperfusion, 1.0 mg of [3H] digoxin was given intravenously, and 2 hr later the hearts were excised and endocardial (endo) and epicardial (epi) samples from each zone were analyzed for [3H] digoxin concentration. In five dogs occluded for 1 hr and reperfused, [3H] digoxin uptake was comparable in endo and epi layers of all three zones. In six dogs reperfused after 2 hr of occlusion, mean (+/-S.E.) [3H] digoxin concentrations (nanograms per gm) were significantly reduced by 54 percent in endo (111 +/-18) and 35 percent in epi (151 +/- 23) layers of the ischemic zone as compared with the mean nonischemic concentration (endo249 +/- 34; epi 239 +/- 34). Border zone endo and epi [3H] digoxin uptake was reduced by 21 and 17 percent, respectively. In six dogs reperfused after 6 hr of occlusion, [3H] digoxin uptake in the ischemic zone was markedly reduced by 85 percent in endo (34 +/- 4) and 60 percent in epi (86 +/- 12) layers as compared with the nonischemic concentration (endo 232 +/- 19; epi 217 +/- 15). Border zone uptake was decreased by 54 percent in endo and 38 percent in epi regions. We conclude that coronary reperfusion between 2 and 6 hr of coronary occlusion is associated with markedly reduced myocardial digoxin uptake, more pronounced in subendocardial regions of ischemic tissue. This alteration in digoxin binding by reperfused ischemic myocardium is consistent with ischemia-induced structural or functional alterations in the putative digitalis receptor, (Na++K+)-ATPase.

Animals↗
PubMed1994

Electrophysiologic and electroretinographic evidence for photoreceptor dysfunction as a toxic effect of digoxin.

PURPOSE: To investigate photoreceptor dysfunction caused by digoxin toxicity. METHODS: First, a patient who experienced toxic side effects from digoxin was studied acutely by serial electroretinography and later during convalescence. Second, the light responses of isolated photoreceptors exposed to varying amounts of digoxin were studied in vitro. RESULTS: Electroretinographic amplitudes were reduced and implicit times were delayed when digoxin levels were elevated and recovered slowly after return to normal digoxin levels. Isolated photoreceptors exhibited concentration-dependent reductions in the magnitude of the light response during digoxin exposure, suggesting reduction in the dark current due to blockade of the sodium-potassium-adenosine triphosphatase pump. Cones were about 50-fold more sensitive than rods. CONCLUSIONS: Reversible rod and cone dysfunction occur during exposure to toxic levels of digoxin. Photoreceptor dysfunction is probably due to the diminution of the dark current in response to the sodium-potassium-adenosine triphosphatase blockade.

Ambystoma↗