digoxin and Magnesium-Deficiency

Congestive heart failure is characterized by contractile dysfunction and frequent complex ventricular ectopy. Despite advances in therapy, mortality from heart failure is substantial, estimated at 10-80 percent per year, and sudden death is common. Magnesium is the second most common intracellular cation, strongly influences cardiac cell membrane function, and is an important catalyst of many enzymatic reactions in the myocyte. Epidemiological studies have implicated magnesium deficit in the genesis of sudden death. Patients with congestive heart failure are predisposed to magnesium deficit for many reasons, including neurohormonal activation, poor gastrointestinal absorption, and drug therapy. Hypomagnesaemia is common in these patients and has been linked to an increased frequency of complex ventricular ectopy. Several early, uncontrolled studies have suggested a beneficial effect of magnesium administration on ventricular arrhythmias in patients with congestive heart failure. Two recent randomized, double blind, placebo-controlled trials have shown that both intravenous and oral administration of magnesium chloride results in a significant reduction in the frequency and complexity of ventricular arrhythmias in patients with congestive heart failure. Magnesium administration is well tolerated and serious adverse effects are rare. The potential mechanisms of the antiarrhythmic action of magnesium and limitations of the available data are discussed. The evidence reviewed suggests that serum magnesium concentrations should be monitored and corrected in patients with congestive heart failure. Ventricular arrhythmias may respond to acute intravenous magnesium administration, which should be considered as early therapy. Further study is needed to define magnesium dose and the effect of concomitant potassium administration. A prospective clinical trial is warranted to determine the chronic effects of magnesium administration in patients with heart failure.

Topics: Absorption; Aged; Anti-Arrhythmia Agents; Death, Sudden; Digoxin; Diuretics; Heart Failure; Humans; Kidney Tubules; Magnesium; Magnesium Deficiency; Middle Aged; Prognosis; Ventricular Fibrillation

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Diuretics; Dogs; Haplorhini; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Potassium

We have examined the effects of magnesium replacement therapy upon post-exercise heart rate and incidence of ventricular premature beats (VPB) in digitalised patients with AF. In 11 such patients, all of whom had serum magnesium concentrations of less than 0.85 mmol/l, treatment with magnesium glycerophosphate was associated with a significant reduction in number of VPBs (982 v. 416 VPB/24 h). Five patients had a high prevalence of ventricular ectopy (greater than 300 VPB/24 h) and these subjects showed particularly marked decreases in VPBs during magnesium treatment (1998 v. 690 VPB/24 h). Three patients had slightly increased QTc intervals but these did not change during magnesium replacement. No significant changes were seen in the mean post-exercise heart rate although 2 subjects did show falls of 25% or more during magnesium replacement. We conclude that treatment with magnesium glycerophosphate may be associated with a decreased prevalence of ventricular ectopy in some digitalised patients with chronic AF and mild-moderate hypomagnesaemia.

Topics: Aged; Atrial Fibrillation; Cardiac Complexes, Premature; Digoxin; Electrocardiography; Exercise; Exercise Test; Female; Heart Rate; Humans; Magnesium; Magnesium Deficiency; Male; Middle Aged

Severe digoxin toxicosis in a 13-year-old mixed-breed dog with dilated cardiomyopathy was successfully treated with i.v. administration of ovine digoxin-specific IgG Fab fragments. Management of this dog following treatment with Fab fragments was complicated by hypomagnesemia and loss of the positive inotropic effect of digoxin.

Topics: Animals; Anti-Arrhythmia Agents; Antihypertensive Agents; Blood Cell Count; Blood Chemical Analysis; Cardiomyopathy, Dilated; Cardiotonic Agents; Digoxin; Dog Diseases; Dogs; Electrocardiography; Enalapril; Female; Immunoglobulin Fab Fragments; Isoproterenol; Magnesium Deficiency; Magnesium Sulfate

Digitalised patients with chronic atrial fibrillation (AF) have a high prevalence of ventricular premature beats (VPB); magnesium deficiency may be a contributory factor. We have used a magnesium loading-test to examine the relationship between ventricular ectopy and magnesium status in 14 digitalised patients with chronic AF. Among seven patients with infrequent VPB (less than 250 24 h-1; mean 107 24 h-1) mean magnesium retention was 10.1% and four subjects retained no significant quantities of magnesium, indicating magnesium repletion. Among the remaining seven patients, mean magnesium retention was significantly higher (33.1%, P less than 0.02) and all patients retained 20% or more of the load given. There was an overall relationship between Mg retention and numbers of VPB (rs = 0.54; P less than 0.05). Magnesium deficiency may be determinant of ventricular ectopy in digitalised patients with chronic AF.

Topics: Aged; Atrial Fibrillation; Cardiac Complexes, Premature; Chronic Disease; Digoxin; Electrocardiography; Female; Humans; Magnesium Deficiency; Male; Middle Aged

1. Eighty-one hospital patients receiving digoxin were separated into groups with and without digoxin toxicity using clinical criteria. Serum digoxin, sodium, potassium, calcium, creatinine, magnesium and monocyte magnesium concentrations were compared. 2. Subjects with digoxin toxicity had impaired colour vision (P less than 0.0001, Farnsworth-Munsell 100 hue test) and increased digoxin levels (1.89 (1.56-2.21) vs 1.34 (1.20-1.47) nmol l-1, P less than 0.01) (mean (95% confidence limits], though there was considerable overlap between two groups. 3. Subjects with digoxin toxicity had lower levels of serum magnesium (0.80 (0.76-0.84) vs 0.88 (0.85-0.91) mmol l-1, P less than 0.01) and monocyte magnesium (6.40 (5.65-7.16) vs 8.76 (7.81-9.71) mg g-1 DNA, P less than 0.01), but there were no significant differences in other biochemical parameters. A greater proportion of toxic subjects were receiving concomitant diuretic therapy (20/21 vs 37/60, P less than 0.05). 4. Magnesium deficiency was the most frequently identified significant electrolyte disturbance in relation to digoxin toxicity. In the presence of magnesium deficiency digoxin toxicity developed at relatively low serum digoxin concentrations.

Topics: Adult; Aged; Aged, 80 and over; Color Vision Defects; Digoxin; Electrolytes; Female; Humans; Magnesium; Magnesium Deficiency; Male; Middle Aged

Topics: Digoxin; Humans; Hypokalemia; Magnesium Deficiency

The efficacy of magnesium therapy in patients with ventricular tachycardia has previously been reported. Recently completed and ongoing studies validate earlier observations that potassium and magnesium supplementation may control other cardiac arrhythmias, particularly in hypomagnesemic patients. Magnesium treatment is a viable therapeutic option when other antiarrhythmic agents fail to suppress ventricular tachycardia, ventricular fibrillation, multifocal atrial tachycardia, atrial fibrillation and supraventricular tachycardia.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Female; Humans; Magnesium; Magnesium Deficiency; Male; Middle Aged; Tachycardia

Hamsters fed a Mg-deficient diet (MD) develop a cardiomyopathy (CM) with foci of myocardial necrosis, calcification, and modest mononuclear and giant cell infiltration. We hypothesize that the lesions are secondary to Ca overload following an increase in myocardial Na due to inhibition of (Na.K)-ATPase and secondary Na-Ca exchange. Nifedipine and digoxin were selected as agents to test this hypothesis. Hamsters were given nifedipine, digoxin, or placebo as sustained release subcutaneous pellets the same day they were started on the MD diet. Animals were killed after 14 days, and MD lesions were quantified in H&E stained slides. Regression analysis showed that nifedipine produced a dose-dependent reduction in lesion abundance (p less than .005) and diameter (p less than .05), while digoxin produced a dose-dependent increase in lesion abundance (p less than .005) and diameter (p less than .005). These results support the hypothesis that MDCM is secondary to Ca overload coupled to inhibition of (Na.K)-ATPase of cardiac myocytes.

Topics: Animals; Calcium; Calcium Channels; Cardiomyopathies; Cricetinae; Digoxin; Dose-Response Relationship, Drug; Heart; Magnesium; Magnesium Deficiency; Male; Mesocricetus; Myocardium; Nifedipine; Sodium; Sodium-Potassium-Exchanging ATPase

Hypomagnesaemia and hypokalaemia are known to predispose to digoxin toxicity. Elderly patients receiving diuretics may be at special risk. A 12-month survey of all patients receiving digoxin at the time of admission to our Geriatric Assessment Unit revealed 16% were hypomagnesaemic, whereas no patient was hypokalaemic. There is a need for greater awareness of the risk of magnesium depletion in elderly patients receiving concurrent diuretic and digoxin therapy.

Topics: Aged; Aged, 80 and over; Digoxin; Diuretics; Drug Therapy, Combination; Humans; Magnesium; Magnesium Deficiency; Potassium; Sodium

Topics: Digoxin; Heart Conduction System; Humans; Magnesium Deficiency

Male Wistar rats were injected intraperitoneally for 3 consecutive days with hydrochlorothiazide (HCTZ; 15 mg/kg), chlorothiazide (CTZ; 100 mg/kg), bendroflumethiazide (BFTZ; 1.5 mg/kg), chlorthalidone (CHLOR; 15 mg/kg), methyclothiazide (METH; 1.0 mg/kg) or metolazone (MET; 1.5 mg/kg). Magnesium content was measured in the hypothalamus, medulla oblongata, cerebral cortex, heart, skeletal muscle and serum. Although there was no consistent alteration of Mg in the serum, skeletal muscle and heart, there was a significant effect on hypothalamic and medullary Mg. Compared to a control value of 17.20 +/- 1.24 mEg/kg in the hypothamus there was a decrease by HCTZ (26%; p less than 0.01), CTZ (24%; p less than 0.01) and BFTZ (30%; p less than 0.01). Similarly, there was a decrease by HCTZ (22%; p less than 0.01), CTZ (30%; p less than 0.01) and BFTZ (25%; p less than 0.01) on Mg in medulla. In contrast MET increases Mg in hypothalamus (31%; p less than 0.01) and medulla (26%; p less than 0.01). Furthermore, digoxin infusion (0.051 ml/min) in animals pretreated with HCTZ induced arrhythmias earlier than in animals receiving digoxin alone (30 vs. 60 min; p less than 0.01). The effects of digoxin toxicity in HCTZ-pretreated animals were partially reversed by CNS administration of 50 micrograms of Mg. These findings strongly suggest that thiazide-induced depletion of Mg in the CNS predisposes to digoxin intoxication.

Topics: Animals; Arrhythmias, Cardiac; Bendroflumethiazide; Brain Chemistry; Digoxin; Diuretics; Electrocardiography; Hydrochlorothiazide; Magnesium; Magnesium Deficiency; Male; Muscles; Myocardium; Rats; Rats, Inbred Strains; Sodium Chloride Symporter Inhibitors

Magnesium (Mg2+) plays a significant role in the electrical stability of the heart and hypomagnesemia may predispose patients to arrhythmias and digitalis toxicity. We measured the serum and skeletal muscle Mg2+ content of patients with chronic Chagasic cardiomyopathy (CCC) during treatment for congestive heart failure and compared it to 15 normal patients who were used to establish the normal values of our population. There is a high frequency of muscle Mg2+ deficiency (66%) in patients with CCC during treatment for heart failure. However, serum Mg2+ is not a sensitive index of deficiency, since hypomagnesemia occurred in only 50% of the patients whose muscle Mg2+ was low. Digitalis toxicity was observed in all muscle Mg2+-deficient patients (100%) and in 25% of patients with normal Mg2+ levels (P less than or equal to 0.05). Ventricular tachycardia (VT) occurred in 75% of muscle Mg2+-deficient patients and in none of the patients with normal magnesium levels (P less than or equal to 0.05). The frequency and severity of premature ventricular contractions (PVC) were higher in muscle Mg2+-deficient patients. We conclude that muscle Mg2+ deficiency is very common in patients with CCC being treated for congestive heart failure and that muscle Mg2+ deficiency defines a higher risk CCC group in terms of digitalis toxicity and severe ventricular arrhythmias such as ventricular tachycardia.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Chagas Cardiomyopathy; Digoxin; Female; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Magnesium Sulfate; Male; Middle Aged; Muscles

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Magnesium Deficiency; Magnesium Sulfate

Topics: Aged; Digoxin; Humans; Magnesium; Magnesium Deficiency; Magnesium Sulfate; Male; Middle Aged; Myocardium; Potassium; Tachycardia

Seven patients with congestive heart failure receiving long-term diuretic treatment (more than three years) experienced idionodal tachycardia in the presence of apparently normal serum digoxin levels. Intravenous bolus administration of magnesium (Mg) sulfate, followed by intramuscular Mg repletion, abolished the digitalis-toxic arrhythmia. The finding of decreased lymphocyte Mg and potassium contents proved the existence of cellular Mg depletion associated with normal serum Mg levels in five patients and with hypomagnesemia in the other two. Decreased cellular Mg content with normal serum Mg level predisposes to digitalis-toxic arrhythmias.

Topics: Aged; Digoxin; Heart Failure; Humans; Lymph Nodes; Magnesium; Magnesium Deficiency; Magnesium Sulfate; Male; Middle Aged; Tachycardia

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Female; Humans; Magnesium Deficiency; Magnesium Sulfate; Male

Serum magnesium estimation was done in 19 children who had heart failure of varied etiology. Five of nine toxic patients and three of 10 nontoxic ones had magnesium deficiency (serum magnesium less than 1.5 mEq. per liter). Mean serum magnesium level was significantly lowered (P less than 0.01) in 19 children and it was further lowered in nine toxic patients (P less than 0.001) as well as in eight hypomagnesemic patients (P less than 0.001) than in healthy control subjects. Mean serum digoxin level in toxic patients was significantly higher than in nontoxic ones (P less than 0.05). In three cases magnesium sulfate was successfully used for the management of cardiac arrhythmias.

Topics: Adolescent; Arrhythmias, Cardiac; Child; Child, Preschool; Digoxin; Heart Defects, Congenital; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Magnesium Sulfate; Rheumatic Heart Disease

Magnesium levels in serum, erythrocytes, skeletal muscle, and bone were measured in 10 patients with valvular heart disease who had received diuretic therapy for heart failure for an average of 3.3 years. Five patients were found to have diminished values for skeletal muscle, indicating significant magnesium deficit. Values for erythrocytes were low in only two of the five patients, and none had low values for serum ultrafiltrate and bone: Magnesium replacement therapy restored skeletal muscle values to normal. Clinical features consistent with the presence of magnesium deficiency were found in all five magnesium-deficient patients. These features were, with few exceptions, corrected by magnesium replacement. The latter also corrected low skeletal muscle potassium values present in all five patients with low skeletal muscle magnesium, four of whom showed clinical features of digoxin poisoning before magnesium therapy was given. Concomitant secondary aldosteronism, inadequate dietary intake, and digoxin therapy had probably augmented the magnesium loss due to diuretic therapy.

Topics: Adult; Aged; Aldosterone; Bone and Bones; Diet; Digoxin; Diuretics; Erythrocytes; Female; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Male; Middle Aged; Muscles; Time Factors

Topics: Animals; Blood Urea Nitrogen; Calcium; Digoxin; Female; Heart; Magnesium Deficiency; Mice; Myocardium; Potassium Deficiency; Time Factors; Tritium

Topics: Aspartic Acid; Coronary Disease; Digoxin; Humans; Magnesium; Magnesium Deficiency; Potassium

Topics: Animals; Blood; Calcium; Carbon Dioxide; Cardiac Output; Cell Nucleus; Chlorides; Digitalis Glycosides; Digoxin; Dogs; Endoplasmic Reticulum; Hemodynamics; Hydrogen-Ion Concentration; Magnesium; Magnesium Deficiency; Mitochondria, Muscle; Myocardium; Osmolar Concentration; Potassium; Renal Dialysis; Sodium; Tritium