digoxin and Hypertrophy--Left-Ventricular

This review focuses on the most recent data published in the field of the sodium-potassium pump inhibitors regarding the hypothetical structure, the secretory stimuli and the pathophysiological implications for particular diseases, such as hypertension. On the basis of the findings published so far, we reconsider and discuss the 'natriuretic hypothesis' for explaining the role of the endogenous sodium-potassium ATPase inhibitor. We propose the ouabain-like factor as a modulator of the renal sodium-potassium pump, that can be considered as a new pharmacological target for hypertension therapy.

Topics: Biological Factors; Cardenolides; Digoxin; Humans; Hypertension, Renal; Hypertrophy, Left Ventricular; Natriuretic Agents; Risk Factors; Saponins; Sodium-Potassium-Exchanging ATPase

Digoxin is widely used for rate control of atrial fibrillation. However, recent studies have reported conflicting results on the association of digoxin with mortality when used in patients with atrial fibrillation. Moreover, the relationship of digoxin use to mortality in hypertensive patients with atrial fibrillation has not been examined.. All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline (n = 134) or who developed atrial fibrillation during follow-up (n = 803), randomly assigned to losartan or atenolol-based treatment, in post-hoc analysis of a substudy of the Losartan Intervention For Endpoint Reduction in hypertension (LIFE) trial. During 4.7 ± 1.1 years of mean follow-up, 167 patients died (17.8%) and 372 (39.7%) were treated with digoxin. In univariate Cox analyses, in-treatment digoxin use, entered as a time-varying covariate, was associated with a 61% higher risk of dying (hazard ratio 1.61, 95% confidence interval 1.18-2.19, P = 0.003). After adjusting for other univariate predictors of death in this population, including age, diabetes, history of ischemic heart disease, stroke, or heart failure, baseline Cornell product, QRS duration, heart rate, serum glucose, creatinine and high-density lipoprotein cholesterol, and a propensity score for digoxin use entered as standard covariates, and for in-treatment heart rate, pulse pressure, and Sokolow-Lyon voltage treated as time-varying covariates, digoxin use was no longer a significant predictor of mortality (hazard ratio 1.04, 95% confidence interval 0.73-1.48, P = 0.839).. In hypertensive patients with ECG left ventricular hypertrophy with existing or new atrial fibrillation, digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use digoxin in this population. These findings suggest that factors other than digoxin use may account for the increased mortality found with digoxin use in some studies.. .

Topics: Aged; Anti-Arrhythmia Agents; Antihypertensive Agents; Atenolol; Atrial Fibrillation; Blood Pressure; Digoxin; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Lipoproteins, HDL; Losartan; Male; Middle Aged; Risk

Cardiac hypertrophy in rats induces a down-regulation of Na(+),K(+)-ATPase alpha(2) isoform, although its functional consequences are poorly understood. Using a mathematical modeling approach that allows differentiation between effects elicited at the receptor and postreceptor level, we studied uptake, receptor binding kinetics, and positive inotropism of digoxin in single-pass Langendorff-perfused hearts of vehicle- and isoprenaline-pretreated rats (2.4 mg/kg per day over 4 days). Digoxin outflow concentration and left ventricular developed pressure data were measured for three consecutive doses (15, 30, and 45 microg) in the absence and presence of the reverse mode Na(+)/Ca(2+) exchange inhibitor 2-[2-[4-(4-nitrobenzyloxyl-)phenyl]ethyl isothiourea methansulfonate] (KB-R7943) (0.1 microM) in perfusate. In hypertrophied hearts, 1) the amount of alpha(2) receptors was reduced to 52% of control levels; 2) the digoxin binding affinity was increased 12-fold due to a decrease in dissociation rate constants of alpha(1) and alpha(2) receptors, and 3) inotropic responsiveness to digoxin the was attenuated on the stimulus-response level, where the coupling ratio of stimulus to response was reduced to 38% of control values. Only in the lowest dose level (15 microg) was this decrease in inotropic potency counterbalanced by the increase in receptor affinity. The Na(+),K(+)-ATPase isoform shift was not responsible for the diminished inotropic effect of digoxin. Coadministration of KB-R7943 significantly reduced cellular response generation at higher digoxin doses to the same limiting stimulus-response relationship in both the vehicle and isoprenaline group.

Topics: Animals; Digoxin; Disease Models, Animal; Down-Regulation; Hypertrophy, Left Ventricular; Isoproterenol; Male; Myocardial Contraction; Protein Binding; Protein Isoforms; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase

Left ventricular hypertrophy commonly complicates chronic renal failure. We have observed that at least one pathway of left ventricular hypertrophy appears to involve signaling through reactive oxygen species (ROS). Green tea is a substance that appears to have substantial antioxidant activity, yet is safe and is currently widely used. We, therefore, studied whether green tea supplementation could attenuate the development of left ventricular hypertrophy in an animal model of chronic renal failure.. Male Sprague-Dawley rats were subjected to sham or remnant kidney surgery and given green tea extract (0.1% and 0.25%) or plain drinking water for the next 4 weeks. Heart weight, body weight, and cardiac Na-K-ATPase activity were measured at the end of this period. To further test our hypothesis, we performed studies in cardiac myocytes isolated from adult male Sprague-Dawley rats. We measured the generation of ROS using the oxidant sensitive dye dichlorofluorescein (DCF) as well as (3H)phenylalanine incorporation following exposure to cardiac glycosides with and without green tea extract.. Administration of green tea extract at 0.25% resulted in attenuation of left ventricular hypertrophy, hypertension, and preserved cardiac Na-K-ATPase activity in rats subjected to remnant kidney surgery (all P < 0.01). In subsequent studies performed in isolated cardiac myocytes, both ouabain and marinobufagenin (MBG) were both found to increase ROS production and (3H)phenylalanine incorporation at concentrations substantially below their inhibitor concentration (IC) 50 for the sodium pump. Addition of green tea extract prevented increases in ROS production as well as (3H)phenylalanine incorporation in these isolated cardiac myocytes.. Green tea extract appears to block the development of cardiac hypertrophy in experimental renal failure. Some of this effect may be related to the attenuation of hypertension, but a direct effect on cardiac myocyte ROS production and growth was also identified. Clinical studies of green tea extract in chronic renal failure patients may be warranted.

Topics: Animals; Blood Pressure; Bufanolides; Cardenolides; Cell Division; Cells, Cultured; Digoxin; Disease Models, Animal; Enzyme Activation; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Myocardium; Myocytes, Cardiac; Nephrectomy; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Rubidium Radioisotopes; Saponins; Sodium-Potassium-Exchanging ATPase; Tea

A 44-year-old woman was admitted to our hospital due to severe hypertension. An electrocardiogram (ECG) and an echocardiogram showed severe left ventricular hypertrophy. Her plasma aldosterone level was elevated. Magnetic resonance imaging revealed a small mass in the right adrenal gland. Before removal of the tumor, plasma endogenous digitalis-like substance (EDLS) levels were elevated. After removal of the tumor, EDLS levels quickly returned to the normal level. A series of echocardiograms and ECGs over a 6- year period after removal of the tumor showed marked regression of cardiac hypertrophy. These findings suggest that EDLS may be closely related to the development of concentric cardiac hypertrophy in primary aldosteronism.

Topics: Adrenal Gland Neoplasms; Adult; Cardenolides; Digoxin; Echocardiography; Electrocardiography; Female; Humans; Hyperaldosteronism; Hypertension; Hypertrophy, Left Ventricular; Saponins

The time course of myocardial uptake of metaiodobenzylguanidine ([123I]MIBG) was studied in 26 patients: seven control subjects (Group 1) and 13 patients with left ventricular hypertrophy secondary to valvular aortic stenosis. Seven of these had received no treatment (Group 2) and six were receiving amiodarone or digoxin (Group 3); six heart transplant recipients were investigated for extra neuronal myocardial uptake of [123I]MIBG (Group 4). The index of myocardial [123I]MIBG uptake was lower in Groups 2 and 3 than in Group 1 (Group 2: 1.42 +/- 0.07, p < 0.001; Group 3: amiodarone, 1.30 +/- 0.10, p < 0.05; digoxin, 1.22 +/- 0.06, p < 0.01; Group I: 1.83 +/- 0.18) and lower in Group 3 than in Group 2. Patients of Group 4 showed a much lower mean index of myocardial [123I]MIBG uptake than the control group (1.07 +/- 0.08, p < 0.001).. 1. Patients with left ventricular hypertrophy secondary to valvular aortic stenosis were found to have lower myocardial [123I]MIBG activity and rapid washout than the control subjects. 2. Amiodarone and digoxin partially inhibited myocardial [123I] MIBG uptake. 3. Extra neuronal myocardial uptake of [123I]MIBG in humans only accounts for 13% of the total cardiac activity.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Amiodarone; Aortic Valve Stenosis; Contrast Media; Digoxin; Female; Heart; Heart Transplantation; Humans; Hypertrophy, Left Ventricular; Iodine Radioisotopes; Iodobenzenes; Male; Middle Aged; Radionuclide Imaging

To evaluate the role of echocardiography in determining the cause of pulmonary edema in pregnancy and the impact this information has on management.. We studied prospectively 45 pregnant or recently postpartum women admitted to an obstetric intensive care unit with pulmonary edema during a 6-year period. Between 1 and 4 days after the onset of pulmonary edema, two-dimensional and M-mode echocardiography was performed, as was continuous, pulsed, and color Doppler echocardiography. The clinical diagnosis obtained from history, physical examination, chest radiograph, and laboratory data was compared with the echocardiographic diagnosis.. Three therapeutically and prognostically distinct groups were identified by echocardiography: 1) those with decreased systolic function (N = 19), 2) those with normal systolic function but increased left ventricular mass and presumed diastolic dysfunction (N = 17), and 3) those with normal hearts (N = 9). During the study period, two patients with systolic dysfunction died and one underwent cardiac transplantation. Patients with systolic dysfunction required short- and long-term treatment with digoxin, diuretics, and angiotensin-converting enzyme inhibitors. Those with diastolic dysfunction received diuretics and long-term antihypertensive therapy. Women with normal hearts required acute therapy only. In 21 patients (47%), echocardiography demonstrated clinically unsuspected findings, which altered the long-term management in 16.. Because clinical and roentgenographic findings do not accurately differentiate patients with respect to the presence and type of cardiac dysfunction, and because these subgroups differ with respect to treatment and probably prognosis, we recommend echocardiography to evaluate all pregnant women with pulmonary edema.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Digoxin; Diuretics; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Oxygen Inhalation Therapy; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Pulmonary Edema