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[Anti-arrhythmia effect of digoxin antibodies in experimental myocardial infarct (arrhythmogenic action of endogenous digoxin-like factor)].

Suggesting endogenous digoxin-like factor (EDLF) to display arrhythmogenic activities in myocardial ischemia (MI), we studied the effect of anti-digoxin antiserum (ADS) on the ventricular fibrillation threshold (VFT) after the coronary ligation in cats and ventricular arrhythmias caused by MI in rats and chloroform-induced hypoxia in mice. Intravenous administration of ADS (5 mg/kg) enhanced VFT in cats with MI from 11.3 +/- 1.6 to 53.3 +/- 8.1 V (M +/- m; p less than 0.01) and significantly reduced ventricular arrhythmias in rats and mice. Our experiments on the isolated electro-stimulated rat atria demonstrated that EDLF is likely not to be an adrenergic cotransmitter in the heart. Possible mechanisms of the arrhythmogenic action of EDLF are discussed.

Animals↗

Cost-effectiveness analysis of the use of digoxin immune Fab (ovine) for treatment of digoxin toxicity.

Each year many people have digitalis toxicity severe enough to require extensive hospital treatment. Digoxin immune Fab[ovine]-Fab fragments (Digibind) have been shown to reverse digitalis toxicity and substantially reduce the risk of death. Data were used from uncontrolled studies of patients treated with Fab fragments as well as clinical, medical care and pharmacokinetic data from symptomatically treated patients to derive estimates of the difference in clinical outcomes and medical care costs when treating with this new drug. Estimates are derived separately for treatment of patients with toxicity that is immediately life-threatening and patients whose manifestations are not immediately life-threatening. Treatment with Fab fragments reduces the probability of dying more for the seriously toxic than for the less seriously toxic patient. Such treatment is generally associated with an increase in total medical care costs for the seriously toxic patients because more of them survive the toxic episode and require additional medical care before discharge from the hospital. For these patients, the estimated cost per life-year saved is between $1,900 and $5,400. When Fab fragments are used to treat less seriously toxic patients, total medical care costs decrease because of an estimated decreased number of days in the coronary care unit and decreased use of pacemakers and other aggressive treatments.

Accidents↗

Volume sensitive hypertension and the digoxin-like factor. Reversal by a Fab directed against digoxin in DOCA-salt hypertensive rats.

Although volume and vasoconstriction have been considered polar elements in a useful pathogenetic hypertension model, many observations suggest that vasoconstriction is involved in volume-dependent hypertension, reflecting the effect of a digitalis-like factor. To examine that possibility, we assessed the depressor responses to Digibind, an antibody Fab directed against digoxin, in a volume-dependent model--DOCA-salt-induced hypertension in rats. Digibind (10 mg/kg, intravenously) induced a gradual blood pressure fall over 2 h that was sustained for 4 h (P < .001). Blood pressure did not fall with Digibind when DOCA was administered without salt or a high-salt intake was provided without DOCA. The intracellular sodium content of the rat aorta, measured by atomic absorption spectroscopy after cold choline wash, was increased in the DOCA-high-salt rats (23.3 +/- 2.7 mEq/L) compared to control rats (12.1 +/- 0.8 mEq/L; P < .001). Aorta sodium content, in parallel with blood pressure, was not increased either by dietary salt supplementation without DOCA, or by DOCA with a low-salt diet. Sodium pump activity was measured as 86Rb uptake into vascular smooth muscle (VSM). Both ouabain-sensitive and ouabain-resistant 86Rb uptake were significantly higher in VSM from DOCA-high-salt animals (P < .01). Despite its effectiveness in reducing blood pressure in this model, Digibind influenced neither VSM sodium content nor 86Rb uptake. The results are consistent with a role for a circulating digitalis-like factor in this volume-dependent model, but events at the VSM level are complex.

Animals↗

Comparison of sotalol with digoxin-quinidine for conversion of acute atrial fibrillation to sinus rhythm (the Sotalol-Digoxin-Quinidine Trial).

We randomized 61 patients with paroxysmal atrial fibrillation (AF) ( < 48 hours from onset) to either sotalol or quinidine treatment. Conversion of rhythm was recorded by Holter monitoring. The starting 80 mg dose of sotalol was repeated at 2, 6, and 10 hours if AF persisted (heart rate > 80 beats/min), and if systolic blood was > or = 120 mm Hg. In the quinidine group, if heart rate > 100 beats/min, it was decreased with intravenous digoxin, whereafter 200 mg of oral quinidine sulfate was given maximally 3 times, each dose 2 hours apart. Conversion of AF to sinus rhythm occurred in 17 or 33 patients (52%) taking sotalol, and in 24 of 28 patients (86%) taking quinidine (p < 0.0001). Electric cardioversion was necessary in 39% of the former and in 14% of the latter group. The mean delay from first trial drug to sinus rhythm with the trial medication was 10.2 +/- 7.6 hours in the sotalol group and 4.0 +/- 2.9 hours in the quinidine group (p < 0.01). Treatment was discontinued in 16 patients taking sotalol (48%) because of asymptomatic bradycardia or hypotension, and in 20 taking quinidine (71%) because of rhythm conversion. Asymptomatic wide complex tachycardia (QRS > 0.12 second) was found in 13% and 27% of patients taking sotalol and quinidine, respectively. The longest RR intervals were 6.4 and 3.8 seconds in the sotalol and quinidine groups, respectively. Oral sotalol did not appear as effective as quinidine sulfate treatment in conversion of paroxysmal AF.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Effect of incubation time and temperature on the interference of digoxin-like immunoreactive substances in digoxin immunoassays.

We have tested the cross-reactivity of digoxin-like immunoreactive substances (DLIS) of cord serum in three commercially available radioimmunoassay systems. We found that there is a marked difference in the specificity of the three antibodies. We were able to eliminate or greatly reduce the interference of DLIS by incubating for 1 h at 37 degrees C. The degree of interference for various cord blood sera is given at three temperature levels and at incubation times ranging from 15 min to 48 h.

Blood Proteins↗