digitoxin and Cardiomegaly

Although the etiology of congestive heart failure is complex, a disturbance of myocardial function due to ischemic heart disease or various forms of cardiomyopathy is by far the leading causative factor. In the early stages of failure various cardiac compensating mechanisms, such as hypertrophy, an increase in contractility and the Frank-Starling mechanism, prevent a major reduction in function. With ongoing failure, myocardial muscle function further deteriorates because of a disturbance in myocardial energy utilization, abnormalities in sympathetic neurotransmitter metabolism, a reduction in beta-receptor density, and, more importantly, a derangement of intracellular calcium transport. The subsequent reduction in cardiac output leads to activation of peripheral neurohumoral mechanisms, including sympathetic stimulation, an increase in circulating norepinephrine, stimulation of the renin-angiotensin-aldosterone system (RAAS), and increased arginine vasopressin production, which result in arterial and venous vasoconstriction, redistribution of tissue blood flow, and an increase in circulating blood volume. The adjustments, however, lead to a vicious circle, where heart function is further depressed by the increase in afterload, whereas the changes in the venous bed and the increase in circulating volume ultimately result in congestion. At this point, digitalis and diuretics alone are no longer sufficiently effective and vasodilators are indicated, possibly combined, in the later stages of failure, with positive inotropic drugs. The angiotensin converting-enzyme inhibiting agents seem particularly useful in this context, presumably because of their complex mode of action, interfering with the neurohumoral systems and peripheral vasculature at multiple sites. Particularly with these agents, a remarkable improvement in clinical condition and exercise capacity has been observed. Even so, the long-term prognosis in patients with severe congestive heart failure is still extremely poor with one-year mortality rates in New York Heart Association class III and IV patients ranging from 34% to 48%. In this article, the pathophysiology of congestive heart failure and the potential of drug therapy are further discussed.

Topics: Autonomic Nervous System; Blood Pressure; Calcium; Cardiomegaly; Cardiotonic Agents; Digitalis; Diuretics; Energy Metabolism; Heart; Heart Failure; Heart Rate; Humans; Myocardial Contraction; Myocardium; Nitrates; Plants, Medicinal; Plants, Toxic; Sodium; Sympathomimetics; Vasodilator Agents

Topics: Adolescent; Adult; Aged; Angiocardiography; Aortic Valve Insufficiency; Cardiomegaly; Child; Child, Preschool; Diet, Sodium-Restricted; Digitalis; Diuretics; Endocarditis, Subacute Bacterial; Heart Failure; Heart Septal Defects, Ventricular; Hemodynamics; Humans; Infant; Infant, Newborn; Middle Aged; Phytotherapy; Plants, Medicinal; Plants, Toxic; Pulmonary Circulation; Pulmonary Valve Stenosis

Topics: Adams-Stokes Syndrome; Adolescent; Adult; Bradycardia; Cardiomegaly; Child; Child, Preschool; Digitalis; Europe; Heart Block; Heart Defects, Congenital; Heart Failure; Humans; Infant; Infant, Newborn; Isoproterenol; Pacemaker, Artificial; Phytotherapy; Plants, Medicinal; Plants, Toxic; Prognosis; Tachycardia; United States

The indication for digitalis treatment was investigated in a controlled and prospective study lasting 12 months in 110 patients on long-term haemodialysis. In ten patients, digitalis was needed because of tachyarrhythmia due to atrial fibrillation and in five because of recurrent pulmonary edema. In 57 patients receiving digitoxin, therapy was discontinued for 4 to 6 weeks, whereas 13 patients not yet treated with digitalis, received digitoxin for 4 weeks. Without digitoxin, trial fibrillation occurred in 4 patients, while no patient experienced atrial fibrillation with digitoxin (P = 0.002). In 13 patients, radiological findings (heart enlargement, pulmonary congestion) were better with digitoxin than without. Thus digitoxin appeared to be clearly indicated in 29% of the haemodialysed patients. Additionally, digitalis was indicated in 31 patients because of heart enlargement, pulmonary congestion and (or) previous pulmonary edema. Initially, 76% of the patients were receiving digitoxin, whereas, after the investigation, the rate was only 57% (P less than 0.001). The prospective frequency of clinically apparent digitoxin intoxication was low (3%) and so were the overall toxic plasma digitoxin levels (5%). Digitalis should be given deliberately but not restrictively to haemodialysis patients, since atrial fibrillation (13%) and heart failure (50%) are frequent and often concealed.

Topics: Adult; Aged; Atrial Fibrillation; Cardiomegaly; Clinical Trials as Topic; Digitalis; Digitoxin; Digoxin; Female; Heart Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Plants, Medicinal; Plants, Toxic; Pulmonary Edema; Renal Dialysis; Tachycardia; Time Factors

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Bradycardia; Cardiac Complexes, Premature; Cardiomegaly; Clinical Trials as Topic; Coronary Disease; Digitalis Glycosides; Digitoxin; Heart Aneurysm; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Kidney Diseases; Lung Diseases; Middle Aged; Spinal Diseases; Tablets; Tachycardia

Thyroxine (T4) administered to rats in a dose of 1 mg/kg for 12 days induces cardiac hypertrophy. The purpose of the present study was to determine the effect of prophylactic + simultaneous digitoxin treatments on the development of T4-induced cardiac hypertrophy. Digitoxin (1 mg/kg body weight) was given per os, once daily for 6 days prior to T4 administration and continued simultaneously with T4 treatment. To determine myocardial enlargement, wet heart weight, myocardial nucleic acid and protein were measured. Digitoxin treatment induced a slight increase in wet ventricle weight and a significant elevation of myocardial RNA content (mg/ventricles) and concentration (mg/g). At the same time, the degree of T4-induced cardiac hypertrophy in digitoxin-treated and untreated animals was nearly the same. On the basis of these results it can be stated that--unlike the cardiac hypertrophy induced by pressure overload or hypoxia,--the T4-induced cardiac hypertrophy is not altered by digitoxin administration.

Topics: Animals; Body Weight; Cardiomegaly; Digitoxin; DNA; Male; Myocardium; Organ Size; Oxygen Consumption; Proteins; Rats; RNA; Thyroxine

Topics: Cardiomegaly; Digitalis; Heart Failure; Humans; Myocardial Contraction; Plants, Medicinal; Plants, Toxic

Topics: Cardiomegaly; Digitalis; Humans; Myocardial Contraction; Plants, Medicinal; Plants, Toxic

Topics: Adult; Aged; Aortic Valve Stenosis; Cardiomegaly; Digitalis; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Necrosis; Plants, Medicinal; Plants, Toxic

Isoproterenol (IPR) administered to rats in a dose of 5 mg/kg for 4 days induces cardiac hypertrophy. The purpose of the present study was to determine the effect of prophylactic + simultaneous digitoxin treatment on the development of IPR-induced cardiac hypertrophy. Digitoxin (1 mg/kg body weight) was given per os, once daily for 6 days prior to IPR administration and continued simultaneously with IPR treatment. To determine myocardial enlargement, wet heart weight, myocardial nucleic acid and protein were measured. Digitoxin treatment induced slight but significant increase in wet ventricle weight and myocardial RNA content (mg/ventricle). At the same time the degree of IPR-induced cardiac hypertrophy in digitoxin-treated and untreated animals was nearly the same. On the basis of these results it can be stated that--unlike the cardiac hypertrophy induced by pressure overload or hypoxia,--the IPR-induced cardiac hypertrophy is not altered by digitoxin administration.

Topics: Animals; Body Weight; Cardiomegaly; Digitoxin; Heart Ventricles; Isoproterenol; Male; Myocardium; Organ Size; Proteins; Rats; RNA

Under conditions of experimental cardiac overload and hypertrophy in rats, a digoxinlike immunoreactivity appears in their serum which is correlated with cardiac growth. It is hypothesized that this is caused by the presence of an endogenous cardiotropic factor displaying cross immunoreactivity with digoxin. Additional evidence of the existence of the putative cardiotropic factor is provided by the finding that the sera of rats with cardiac overload displaying digoxinlike immunoreactivity stimulate the multiplication of rat cardiac myocytes in the tissue culture. This factor may be an adrenal steroid different from corticosterone and aldosterone. The name endocardin or endocardiotonin for this substance is suggested.

Topics: Adrenal Glands; Animals; Cardiomegaly; Digitoxin; Digoxin; Heart; Male; Organ Size; Rats; Rats, Inbred Strains

Topics: Adrenal Glands; Animals; Aorta; Biological Products; Cardiomegaly; Cardiotonic Agents; Digitoxin; Digoxin; Heart; Heart Ventricles; Ligation; Male; Organ Size; Rats

A significant positive correlation between heart weight and adrenal weight was found in rats with myocardial hypertrophy induced by experimental hyperthyroidism or ligation of the abdominal aorta. The simultaneous administration of digitoxin partly inhibited myocardial hypertrophy after ligation of the abdominal aorta, but not after experimental hyperthyroidism. Digitoxin also inhibited adrenal hypertrophy after ligature of the abdominal aorta but, again, not after experimental hyperthyroidism. The possible existence of an endogenous cardiotropic hormone participating in the development of cardiac hypertrophy from overloading is discussed.

Topics: Adrenal Glands; Animals; Aorta, Abdominal; Cardiomegaly; Digitoxin; Hyperthyroidism; Ligation; Male; Myocardium; Organ Size; Rats; Rats, Inbred Strains; Thyroid Hormones

The synthesis of poly(A) containing RNA was increased in heart of non-digitalized and digitalized rats after aortic constriction, the increase being of the same degree as that of the RNA lacking this sequence. No differences were found, either in the absence or presence of polyuridylic acid, in the incorporation of radioactivity into protein by cardiac ribosomes isolated from animals treated differently. It may be concluded, that after the constriction of the aorta the synthesis of mRNA proceeds at a similar rate as that of the bulk RNA, and that the treatment of the animals with digitoxin does not abolish the stimulus for hypertrophy.

Topics: Animals; Aorta, Abdominal; Cardiomegaly; Digitoxin; Male; Muscle Proteins; Myocardium; Poly A; Rats; Ribosomes; RNA

The effect of prophylactic digitalization on the development of left ventricular hypertrophy was studied in adult rats. Digitoxin, 0.1 mg/100 g body wt or solvent was given daily for 1 wk prior to either aortic constriction or sham operation and was continued until the animals were killed, either 1 or 4 wk after surgery. A hemodynamic study was done in those animals killed 1 wk after surgery; hearts of all animals were examined for evidence of myocardial hypertrophy. Constriction of the ascending aorta had no significant effect on cardiac output but did reduce peak flow velocity and flow acceleration. An increase in left ventricular mass, RNA, and hydroxyproline was found in the animals with aortic constriction. Digitoxin treatment did not alter peak flow velocity or flow acceleration, but did significantly increase isovolumic (dP/dt)P-1. Digitoxin had no effect on body weight, heart weight, RNA, or hydroxyproline in either the sham-operated animals or in the animals with aortic constriction. Therefore, despite plasma digitoxin levels sufficient to affect myocardial contractility, left ventricular hypertrophy still developed after aortic constriction.

Topics: Animals; Aorta; Blood Pressure; Cardiomegaly; Collagen; Coronary Circulation; Digitoxin; Female; Heart; Hydroxyproline; Ischemia; Myocardial Contraction; Myocardium; Rats; RNA

Topics: Animals; Aortic Valve Stenosis; Cardiomegaly; Deslanoside; Digitalis Glycosides; Digitoxin; Digoxin; Male; Medigoxin; Rats

It is generally agreed that cardiac hypertrophy is accompanied by the hyperplasia of connective tissue cells. In the present work, collagen metabolism was studied in the heart of nondigitalised and digitalised rats after the constriction of the aorta. The activity of prolyl hydroxylase was maximally increased 2 days after the operation. The incorporation of proline into collagen hydroxyproline increased without any increase in the specific radioactivity of free intracellular proline, the peak labelling of collagen occurring at 4 days. Although the treatment of the rats with digitoxin prevented the development of cardiac hypertrophy and an increase in collagen labelling, an increase in the activity of prolyl hydroxylase was observed. The intracellular free proline pool and its specific radioactivity were significantly lower in digitalised rats as compared with non-digitalised rats. The results indicate that constriction of the aorta is accompanied by an activation of connective tissue cells leading to increased synthesis of collagen. However, digitoxin treatment can prevent the increase in collagen labelling, possibly by inhibiting the amino acid transport, but it is unable to remove the stimulus for hypertrophy.

Topics: Aminoisobutyric Acids; Animals; Cardiomegaly; Collagen; Digitoxin; Extracellular Space; Heart; In Vitro Techniques; Male; Myocardium; Procollagen-Proline Dioxygenase; Proline; Rats

Bilateral compression of the adrenal glands combined in mononephrectomy and followed by the imposition of a high NaC1 intake resulted in severe hypertension in all rats so treated. It was accompanied by enlargement of the heart, kidneys, and adrenal glands, atrophy of the thymus, and the occurrence of severe nephrosclerosis. Digitoxin treatment delayed the onset, reduced the incidence, and ameliorated the magnitude of the hypertensive response in such animals; it also reduced the degree of cardiac hypertrophy and the severity of nephrosclerosis and completely prevented enlargement of the adrenals and kidneys and atrophy of the thymus.

Topics: Adrenal Glands; Animals; Blood Pressure; Body Weight; Cardiomegaly; Digitoxin; Female; Hypertension; Kidney; Nephrosclerosis; Organ Size; Rats; Thymus Gland

In cardiac hypertrophy the total content of collagen is increased in the myocardium. The first indicator of the increased activity of connective tissue cells is an increase in the activity of prolyl hydroxylase of the myocardium. This is later followed by an increase in the rate of collagen synthesis and subsequently collagen is accumulated in the myocardium. Digitoxin treatment prevents the hypertrophy and the accumulation of proteins to the myocardium. This effect of digitoxin is, at least partly, explained by a decreased transport of amino acids into the cells, The results emphasize the importance of amino acid supply to the process of hypertrophy.

Topics: Animals; Cardiomegaly; Collagen; Digitoxin; Myocardium; Rats

Removal of the pericardium in combination with a mild exercise programme of swimming resulted in a significant increase in heart weight and heart weight/body weight ratio of young rats. Heart weight/body weight ratios were 3.46+/-0.25 in the sedentary control animals, 4.16+/-0.26 in pericardiectomized animals swimming 2 h each day, and 4.60+/-0.22 in pericardiectomized animals swimming 6h/d. The effect of pericardiectomy on the development of cardiac hypertrophy is additive to that of mild exercise (2h/d) but not to prolonged exercise (6h/d). The administration of digitoxin significantly decreased the development of cardiac hypertrophy in pericardiectomized animals that were exercised for 2 h/d but not those exercised for 6 h/d. These findings further substantiate the physiological effect on the heart of the pericardium. The effects of pericardiectomy should be considered in experimental studies of cardiac hypertrophy and in clinical studies involving cardiac surgery.

Topics: Animals; Body Weight; Cardiomegaly; Digitoxin; Female; Organ Size; Pericardium; Physical Exertion; Rats; Swimming

To determine the effect of prolonged digitoxin administration on contractile function of nonfailing myocardium, right ventricular papillary muscle mechanics were examined after 6 or 24 wk of glycoside administration to control and pulmonary artery banded cats. Resting length-tension relations were not affected by digitoxin; however, isometrically developed force and the maximal rate of force development at the peak of the length-tension curve were increased in all treated groups. In untreated animals, banding resulted in a 28% incidence of deaths from heart failure. 6 wk after constriction, contractile function was depressed whereas normal function was observed 24 wk after banding. Digitoxin significantly reduced mortality from heart failure and enhanced the recovery of contractile function; contractile function in the 6 wk banded treated group approached that of untreated control and 24-wk banded groups. The long-term effects of digitoxin on contractile function were not importantly related to the temporal association between banding and institution of glycoside administration. Development of myocardial hypertrophy was comparable in treated and untreated banded groups.These results demonstrate that a significant positive inotropic effect persists in both normal and nonfailing hypertrophied myocardium during chronic digitoxin administration.

Topics: Animals; Body Weight; Cardiac Output; Cardiac Volume; Cardiomegaly; Cats; Digitoxin; Disease Models, Animal; Heart Failure; Myocardial Contraction; Papillary Muscles; Stimulation, Chemical; Time Factors

Topics: Animals; Cardiomegaly; Digitoxin; Digoxin; Hypoxia; Male; Rats

Topics: Alcoholism; Cardiomegaly; Cell Membrane Permeability; Diagnosis, Differential; Diet Therapy; Digitalis; Diuretics; Electrocardiography; Electrolytes; Ethanol; Heart Conduction System; Heart Diseases; Heart Failure; Humans; Mitochondria; Myofibrils; Nutrition Disorders; Plants, Medicinal; Plants, Toxic; Substance Withdrawal Syndrome; Thiamine; Wolff-Parkinson-White Syndrome

Topics: Altitude; Animals; Body Weight; Cardiomegaly; Digitoxin; Heart Ventricles; Hemodynamics; Hypoxia; Organ Size; Rats

Topics: Age Factors; Aged; Atrial Fibrillation; Cardiac Complexes, Premature; Cardiomegaly; Digitalis; Electrocardiography; Female; Heart Block; Heart Conduction System; Heart Rate; Humans; Male; Myocardial Infarction; Plants, Medicinal; Plants, Toxic

Topics: Adrenal Gland Diseases; Adult; Arrhythmias, Cardiac; Athletic Injuries; Autopsy; Cardiomegaly; Cholelithiasis; Coronary Vessel Anomalies; Coronary Vessels; Death, Sudden; Digitalis; Electrocardiography; Heart Conduction System; Heart Diseases; Humans; Male; Military Medicine; Myocarditis; Myocardium; Phytotherapy; Plants, Medicinal; Plants, Toxic; Pulmonary Edema; Quinidine; Thymus Gland

Topics: Body Weight; Cardiac Catheterization; Cardiomegaly; Codeine; Cough; Diagnosis, Differential; Digitalis; Dyspnea; Female; Hemoptysis; Humans; Leiomyosarcoma; Lung Neoplasms; Middle Aged; Pericardial Effusion; Phytotherapy; Plants, Medicinal; Plants, Toxic; Pulmonary Artery; Pulmonary Valve Stenosis; Respiratory Function Tests

Topics: Animals; Aorta, Abdominal; Cardiomegaly; Constriction; Digitoxin; DNA; Leucine; Ligation; Male; Myocardium; Organ Size; Protein Biosynthesis; Rats; RNA; Time Factors; Tritium; Uridine; Water

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Aorta; Blood Pressure; Cardiomegaly; Dactinomycin; Digitoxin; Kinetics; Leucine; Male; Myocardium; Phenylalanine; Phosphoric Acids; Phosphorus Isotopes; Puromycin; Rats; RNA; Time Factors; Tritium

Topics: Animals; Cardiomegaly; Digitoxin; Heart; Hypoxia; Mice; Organ Size; Respiratory Insufficiency

Topics: Animals; Cardiomegaly; Digitoxin; Heart Failure; Hypertension; Rats

Topics: Ascites; Cardiomegaly; Chlorothiazide; Digitoxin; Diuretics; Electrocardiography; Endocardial Fibroelastosis; Heart Atria; Heart Failure; Humans; Organomercury Compounds; Pathology

Topics: Aneurysm, False; Anticoagulants; Cardiomegaly; Digitoxin; Heart Aneurysm; Heart Failure; Heart Ventricles; Humans; Infarction; Myocardial Infarction; Pathology; Pericardium; Quinidine

Topics: Cardiomegaly; Coronary Disease; Digitalis; Digitalis Glycosides; Diuretics; Drug Therapy; Heart Diseases; Heart Failure; Humans; Hypertension

Topics: Adolescent; Cardiomegaly; Digitalis; Electrocardiography; Female; Heart Aneurysm; Heart Auscultation; Heart Septum; Heart Valve Diseases; Humans; Maternal Death; Maternal Mortality; Pathology; Prednisone; Pregnancy; Pregnancy Complications, Cardiovascular; Tachycardia

Topics: Anemia, Sickle Cell; Black People; Cardiomegaly; Child; Digitalis; Digitalis Glycosides; Electrocardiography; Heart Failure; Humans; Hypertension; Hypertension, Pulmonary

Topics: Arrhythmias, Cardiac; Cardiomegaly; Digitalis; Digitalis Glycosides; Heart Valve Prosthesis; Humans; Hypokalemia; Mitral Valve; Toxicology; Ventricular Fibrillation

Topics: Angiocardiography; Cardiomegaly; Child; Coronary Vessel Anomalies; Diagnosis, Differential; Digitalis; Digoxin; Drug Therapy; Electrocardiography; Endocardial Fibroelastosis; Glycogen Storage Disease; Humans; Infant; Mumps; Myocarditis; Skin Tests

Topics: Cardiomegaly; Digitalis; Electrocardiography; Humans; Hypertrophy, Left Ventricular

Topics: Cardiomegaly; Digitalis; Electrocardiography; Hypertrophy, Left Ventricular; Plant Extracts

Topics: Cardiomegaly; Digitalis; Heart; Humans

Topics: Cardiomegaly; Digitalis; Digitalis Glycosides; Plant Extracts