medigoxin and Arrhythmias--Cardiac

Pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419) reversed congestive heart failure and various arrhythmias, influenced the NO-system and showed no proarrhythmic effect. In therapy analogy, we challenged rats with digitalis, to show attenuation by BPC 157 and the relation between the NO-system and digitalis toxicity. (i). BPC 157 prophylactic effect. Development of cumulative intravenous digitalis toxicity, BPC 157 (50 microg, 10 microg, 10 ng/kg applied intravenously immediately before a methyldigoxin increment regimen (2.0/1.5/1.5/1.0 mg/kg at 15 min-intervals, total dose 6.0 mg/kg/45 min)) reduced the number of ventricular premature beats, prolonged the time before onset of ventricular tachycardia, reduced ventricular tachycardia and AV-block duration (microg-regimes) or reduced mainly the AV-block duration (ng-regimen). (ii). BPC 157 therapy. Advanced methyldigoxin toxicity (6.0 mg/kg i.v. bolus). BPC 157 applied at the 20th second of the grade 3 AV-block shortened AV-blocks, mitigated a further digitalis toxicity course. Ventricular tachycardias were either avoided (50 microg), or markedly reduced (10 microg, 10 ng). Fatal outcome was either avoided (50 microg), reduced (10 microg), or only delayed (10 ng) (iii) BPC 157, L-NAME, l-arginine, L-NAME+l-arginine application. L-NAME-application (5 mg/kg i.p.) aggravated methyldigoxin-arrhythmias. l-arginine (200 mg/kg i.p.) alone had no effect but blunted L-NAME-exaggeration (L-NAME+l-arginine). In this respect, BPC 157 (50 microg/kg i.p.) was prophylactically and therapeutically more effective: the antagonism of L-NAME with BPC 157 produced an effect similar to BPC 157 alone. In conclusion, digitalis-induced arrhythmias in rats could be prevented and counteracted by pentadecapeptide BPC 157, mainly through an interaction with the NO-system.

Topics: Animals; Anti-Arrhythmia Agents; Anti-Ulcer Agents; Arginine; Arrhythmias, Cardiac; Heart Rate; Male; Medigoxin; NG-Nitroarginine Methyl Ester; Nitric Oxide; Peptide Fragments; Proteins; Rats; Rats, Wistar

Three cases of patients with symptoms of digitalis overdosage were presented. The principal manifestations included complex supraventricular dysrhythmias and atrio-ventricular conduction disturbances. In the discussion a special attention was paid to digitalis dosage. Multiple factors influencing plasma concentration of digitalis including pharmacokinetics, bioavailability and drug interactions with glycosides were described. Short review of toxic manifestations of digitalis was made and the treatment of digitalis intoxication was outlined.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrioventricular Node; Captopril; Digitalis; Digitalis Glycosides; Drug Interactions; Drug Overdose; Drug Therapy, Combination; Female; Heart Conduction System; Humans; Male; Medigoxin; Middle Aged; Pentoxifylline; Plants, Medicinal; Plants, Toxic; Tachycardia, Supraventricular

The aim was to compare the binding characteristics of a highly purified digoxin specific antigen binding fragment (digoxin immune Fab: DIGIBIND) with digoxin and with two commonly used derivatives of digoxin, beta methyl digoxin and beta acetyl digoxin, and to assess its ability to abolish the arrhythmogenic effects of these digitalis glycosides.. The binding characteristics of DIGIBIND with digoxin, beta methyl digoxin, and beta acetyl digoxin were assessed in vitro by measuring their ability to inhibit the binding of DIGIBIND to 3H-digoxin. From these studies the affinities of the interactions between DIGIBIND and these glycosides, and the binding capacity of DIGIBIND for each of these glycosides, could be measured. The ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin, beta methyl digoxin, and beta acetyl digoxin was assessed using an in vivo anaesthetised guinea pig model (n = 36, weight 300-400 g), in which these glycosides were infused intravenously (50 micrograms.kg-1 x min-1) until the onset of ventricular arrhythmias, at which point the total amount of glycoside given was calculated. A single bolus dose of either vehicle or DIGIBIND was then given intravenously, and the time to restoration of normal cardiac rhythm noted. After the administration of DIGIBIND, a second infusion of the same glycoside was given to reinitiate the ventricular arrhythmias. The time to onset of the arrhythmias was noted, and the additional amount of glycoside given calculated.. In vitro studies showed the binding of DIGIBIND to 3H-digoxin to be inhibited by digoxin and by the two derivatives. The affinities of these interactions with DIGIBIND were significantly different, that for digoxin being some twofold greater than that for beta methyl digoxin and beta acetyl digoxin. The ED50 concentrations were 14.1 (95% CI 12.2, 15.2), 29.2(26.1, 32.7), and 36.2(33.0, 39.8) nM, respectively. However, there were no significant differences between these glycosides in their binding capacities. The in vivo studies showed that intravenous infusion of digoxin, beta methyl digoxin, or beta acetyl digoxin induced similar ventricular arrhythmias. The onset of the arrhythmias was clearly discernible, and required a significantly lower dose of digoxin compared with that of beta methyl digoxin and beta acetyl digoxin. These doses were 667(SEM 55), 868(33), and 854(40) nmol.kg-1, respectively. Termination of the infusion had no effect on the arrhythmias, and in those animals which received a bolus intravenous injection of saline there was no return to normal cardiac rhythm. By contrast, in animals which received a bolus intravenous injection of DIGIBIND, there was complete abolition of the arrhythmias within 4-6 min. Although the dose of DIGIBIND given to abolish digoxin induced arrhythmias was approximately 25% less than that given to abolish beta methyl digoxin and beta acetyl digoxin induced arrhythmias (p < 0.05), the time to restoration of normal cardiac rhythm after DIGIBIND was not significantly different for digoxin compared with beta methyl digoxin and beta acetyl digoxin, at 4.6(0.9), 4.9(0.8), and 5.7(0.8) min, respectively. To reinitiate the arrhythmias in those animals which had received DIGIBIND, a dose of glycoside was required which was not significantly different from that given prior to the DIGIBIND. This observation therefore confirmed the stoichiometric relationship between DIGIBIND and each of the glycosides in respect of the neutralising action of DIGIBIND in abolishing the arrhythmogenic effects of these agents.. Although there is some small difference in the affinities of the binding interactions, there is no difference in the binding capacities of DIGIBIND for digoxin, beta methyl digoxin, or beta acetyl digoxin in vitro. These binding interactions are manifest as the ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin and the two derivatives in vivo.

Topics: Acetyldigoxins; Animals; Antigen-Antibody Reactions; Arrhythmias, Cardiac; Digoxin; Guinea Pigs; Immunoglobulin Fab Fragments; Male; Medigoxin

A retrospective study of two groups of patients with a different plasma digoxin level (Group A: digoxin greater than or equal to 2 ng/ml, n = 32, Group B: digoxin less than 2 ng/ml, n = 34; total n = 66) showed a significantly lower creatinine clearance (p less than 0.05) in group A. This group also showed a weak correlation between the digoxin level and the length of observation (R = + 0.31, p less than 0.05, n = 29). Furthermore, a weak correlation between digoxin level and the ratio of average daily dosage to creatinine clearance was found for the total sample (R = + 0.30, p less than 0.05, n = 66). Patients treated for less than 7 days and with a higher digoxin level also had a higher dosage and worse renal function (p = 0.05, p = 0.01, respectively). A weak correlation also existed between the digoxin level and creatinine clearance and body weight for the whole sample (R = -0.29, p less than 0.05; R = -0.29, p less than 0.01, respectively; n = 66). The latter correlation was also found within each group. Apart from renal function, the medication taken and body weight seem to be useful variables in predicting impending elevation of the digoxin level. In this study these variables were found to be better suited for the said purpose than the ECG. These conclusions remain to be confirmed by means of a prospective study.

Topics: Acetyldigoxins; Age Factors; Arrhythmias, Cardiac; Body Weight; Creatinine; Digoxin; Dosage Forms; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrocardiography; Female; Humans; Kidney Function Tests; Male; Medigoxin; Risk

Topics: Animals; Arrhythmias, Cardiac; Chick Embryo; Digoxin; Fetal Heart; Heart; Heart Arrest; Medigoxin; Myocardial Contraction

The antiarrhythmic potency of mexiletine was evaluated on three groups of guinea-pig isolated hearts. Arrhythmias were induced (a) with digitalis intoxication, (b) with hypoxia followed by reoxygenation and (c) with ischaemia followed by reperfusion. Mexiletine 10 microM was found to be very effective against all three types of arrhythmias in all three groups. The electrophysiological effects of mexiletine were then studied on sheep cardiac Purkinje fibres manifesting oscillatory afterpotentials and triggered automaticity induced by barium or strophanthidin. Mexiletine 10 microM consistently decreased the amplitude of oscillatory afterpotentials and blocked subsequent triggered activity in sheep Purkinje fibres. In contrast, mexiletine 10 microM had no significant effect on Vmax in normal, barium- and strophanthidin-treated preparations. The results are discussed in relation to the mechanisms of antiarrhythmic action of mexiletine.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Barium; Coronary Circulation; Depression, Chemical; Guinea Pigs; Heart Conduction System; Heart Ventricles; In Vitro Techniques; Medigoxin; Mexiletine; Myocardial Contraction; Oxygen; Propylamines; Purkinje Fibers; Sheep; Strophanthidin

The increasing use of amiodarone as antiarrhythmic drug has raised the possibilities of dangerous effects from amiodarone-digitalis interaction. We have studied twelve patients who were taking digitalis and to whom amiodarone was administered because of arrhythmias. We found a 75,42% increase of digitalis plasma levels (p less than 0,001) in the early days of amiodarone therapy, and a 52,1% increase (p less than 0,001) in the medium term. An inverse correlation was found (r = -0,65; p less than 0,05) between the plasma levels of digitalis during the steady-state control period and during the following 2-to-6 months evaluation. Acute episodes of cardiac failure caused in our patients an abrupt increase of digitalis plasma levels: in three patients digitalis toxicity occurred. Based on our experience, we recommend that the dose of digitalis be halved when the two drugs are given together in patients with various degree of cardiac failure; moreover digitalis plasma levels should be frequently monitored in these patients. On the other hand digitalis administered according to age, sex, weight, kidney function, together with amiodarone, can be given at full dosage in patients without cardiac failure.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digitalis Glycosides; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Male; Medigoxin; Middle Aged

To date, 16 patients with severe glycoside poisoning have been treated with Fab as part of the clinical trial for efficacy and tolerance. The ages of the patients ranged from 4 to 77 years. In 13 cases, the substance was taken with suicidal intent. The following were considered to be indications for the use of Fab: the appearance of life-threatening arrhythmias as high-grade atrioventricular conduction disorders, multifocal ectopic beats, ventricular tachycardia, and relapsing ventricular fibrillation in 5 cases. Serum digoxin concentrations were between 3.8 and 78 ng/ml before the start of treatment. The amount of Fab administered was 240-800 mg, in the majority of cases 480 mg. Regression of the arrhythmias was seen in all patients during or shortly after the Fab infusion. There was a rapid fall in the free digoxin in the serum to levels that were no longer measurable and a marked rise in bound digoxin with a simultaneous intensive excretion of bound digoxin in the urine. Fab therapy is considered to be a major advance in the treatment of severe, previously fatal, glycoside poisoning. No notable side effects were observed, nor were there any allergic reactions to foreign protein.

Topics: Acetyldigoxins; Adolescent; Adult; Aged; Antibodies; Arrhythmias, Cardiac; Child, Preschool; Digoxin; Dose-Response Relationship, Drug; Female; Humans; Immunoglobulin Fab Fragments; Male; Medigoxin; Metabolic Clearance Rate; Middle Aged; Suicide, Attempted

Topics: Adolescent; Adult; Age Factors; Aged; Arrhythmias, Cardiac; Child; Child, Preschool; Digitalis Glycosides; Digoxin; Heart Block; Humans; Infant; Infant, Newborn; Lanatosides; Medigoxin; Middle Aged

In clinical Arrhythmology it is often necessary to associate digitalis and antiarrhythmic agents. This calls for study of possible interaction between the employed drugs. We found a statistically significant correlation between digitalis and amiodarone plasma level in patients on long term treatment with both drugs. A statistically significant linear correlation between plasma amiodarone level and digoxin (0.25 mg/day) or beta-methyldigoxin (0.20 mg/day) was documented in 33 patients. 23 patients had been treated with these drugs for paraxysmal reciprocating supraventricular tachycardia since an average of 52 months (computerized follow-up). (Amiodarone average weekly dose was 1078 +/- 168 mg after a loading dose of 12 gm given over one month). 10 patients were on chronic treatment with higher weekly doses of amiodarone (average dose 2380 +/- 731 mg per week). Thyroid function tests (T4; T3; T3UP; TSH; rT3) were checked in every patients. Further studies are warranted to understand the mechanism of the interaction between amiodarone and digitalis. As a clinical implication we point out that amiodarone-digoxin (or betamethyldigoxin) interaction in our patients has neither resulted in over-therapeutic plasma level nor in signs of digitalis toxicity.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Female; Humans; Male; Medigoxin; Middle Aged; Tachycardia, Paroxysmal

Topics: Arrhythmias, Cardiac; Digoxin; Heart; Heart Failure; Humans; Injections, Intravenous; Medigoxin; Pacemaker, Artificial