UMLS:C0018801 - FACTA Search

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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Potentially malignant ventricular arrhythmias are common in chronic heart failure. The aggravation of such arrhythmias has many causes in these patients and cannot be predicted. Therefore, proarrhythmia due to PDE-inhibitors which increase cytosolic calcium levels by specific inhibition of the degradation of cyclo-AMP may be difficult to recognize. A retrospective analysis of 24-h Holter ECG was performed in 31 patients (NYHA classes III and IV) under long-term enoximone therapy. At baseline, 68% of the patients had ventricular couplets and nonsustained ventricular tachycardia. After a mean treatment period of 7 months, 10% of the patients showed a significant increase, 16% a significant decrease (greater than 90%) of ventricular couplets and salvos, and an additional 32% of the patients showed a significant decrease (greater than 70%) of single PVCs. The change of the arrhythmia profile was not related to the clinical course in these patients. Furthermore, 24-h Holter recordings were analyzed in a randomized long-term trial with captopril and enoximone that included 20 patients of NYHA class II. Despite comparable baseline findings, a reduction of cardiopulmonary exercise capacity was observed in patients treated with enoximone, but not with captopril. However, the arrhythmia profile was similar in both treatment groups. These findings suggest that, in most patients with advanced chronic heart failure, long-term enoximone therapy is not associated with an important increase of ventricular arrhythmias. According to the 24-h Holter findings of the European Enoximone Data Bank, proarrhythmia can be expected in 12% of all patients. Control of the arrhythmia profile, however, is mandatory, because the incidence of proarrhythmia cannot be predicted in the individual patient.
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PMID:[Enoximone and ventricular arrhythmia in chronic heart failure]. 183 3

A model of heart failure produced by rapid ventricular pacing in the conscious dog instrumented with a conductance catheter to monitor instantaneous left ventricular volume has been developed. This experimental model is capable of analysis of the left ventricular pressure-volume relationship on a beat-to-beat basis, and has been used to assess ventricular function serially in the progress of heart failure and effects of pharmacological intervention. In seven dogs the magnitude of cardiotonic effects were significantly attenuated after development of heart failure. These findings support the concept that in the failing heart there is subsensitivity to beta-adrenergic stimulation in proportion to the severity. The failing heart was characterized by incomplete left ventricular relaxation. Dobutamine improved left ventricular early relaxation but did not affect chamber distensibility. In contrast new phosphodiesterase inhibitor, E-1020, improved ventricular distensibility with less marked changes in active relaxation; improved left ventricular relaxation appeared to be mediated by increased systolic shortening with enhancement of internal restoring forces, and improved distensibility by accelerated function of sarcoplasmic reticulum through increased intracellular cyclic AMP.
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PMID:Mechanics of contraction and relaxation of the ventricle in experimental heart failure produced by rapid ventricular pacing in the conscious dog. 191 38

Reports in the literature have suggested that a complex alteration in beta-receptor pathway takes place in failing human myocardium. The purpose of our study was to evaluate the beta-adrenergic receptor system in an experimental model of heart failure induced by monocrotaline in rats. Monocrotaline, administered with a single intraperitoneal injection (50 mg/Kg), causes pulmonary hypertension and right ventricular hypertrophy, associated with congestive heart failure. beta 1 and beta 2-receptors were characterized in the right ventricle by direct radioligand binding utilizing [125I] Iodocyanopindolol and selective beta 1-(CGP 20712A) and beta 2-(ICI 118551) antagonists. Adenylate cyclase was measured in basal condition and in the presence of different stimulators as isoproterenol with ICI 118551 (beta 1-receptor-stimulated activity), isoproterenol with CGP 20712A (beta 2-receptor-stimulated activity), Gpp(NH)p, NaF and forskolin. In the right ventricle of the failing hearts the beta 1-receptor density decreased selectively (-55.8%) while the beta 2-receptor density was unchanged. Modifications in the adenylate cyclase system were demonstrated: a reduction in the basal and beta 1- and beta 2-stimulated adenylate cyclase activity; a decrease in adenylate cyclase activation elicited by Gpp(NH)p, but not by forskolin and NaF. In conclusion, these data suggest that in monocrotaline-induced heart failure in the rat there is a selective beta 1-receptor down-regulation and an impaired coupling efficiency of G proteins. These results are in line with biochemical changes found in patients with heart failure.
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PMID:[The adrenergic beta system in an experimental model of heart failure]. 196 56

Catecholamines play an essential role in the activation of the cardiovascular system and in the regulation of energy metabolism in a variety of physiological conditions. Many of these effects are mediated through beta-adrenoceptors located on cell membranes. Binding of catecholamines to beta-adrenoceptor increases the concentration of intracellular cyclic AMP which in turn activates protein kinase A. This enzyme phosphorylates a number of other intracellular enzymes influencing cell metabolism and functions. The primary structures of the receptor and its topography in the cell membrane as well as its binding domains have been partially clarified. In studies of the human beta-adrenergic receptors blood lymphocytes have mostly been used as model cells. These cells carry receptors of mainly the beta 2-subtype. The adequacy of this model system has been demonstrated in several studies. In clinical work receptor assays have had limited use until now. However, studies on the pathophysiology of the adrenergic system in several diseases have revealed that receptor alterations may constitute an important factor in the disease process. Measurements of adrenergic receptors may also have increasing usefulness in determining optimal drug concentrations. Our own studies have primarily focused on physiological adjustments in the beta-adrenergic system during acute or prolonged physical exercise as well as receptor changes in heart failure, muscle diseases and the alcohol withdrawal syndrome. We have also explored receptor dynamics during therapy with beta-blocking agents. These studies, briefly reviewed in this communication, have led to the following conclusions: (1) High aerobic capacity is associated with an increased density and ability of lymphocytic beta-adrenoceptors to respond to catecholamines. (2) Both short-and long-term physical exercise induce a rapid up-regulation and more effective functioning of lymphocytic beta-adrenoceptors. (3) Administration of beta-blocking drugs is associated with a subnormal exercise-induced up-regulation and decreased functioning of the lymphocytic beta-adrenoceptors. (4) The exercise-provoked up-regulation and improved functioning of beta-adrenoceptors is blunted in heart failure patients. (5) Patients with Duchenne-type of muscular dystrophy have a reduced number of lymphocytic beta-adrenoceptors. (6) In chronic alcoholics the lymphocytic beta-adrenoceptor level is subnormal but during abrupt ethanol withdrawal a rapid increase in the number and functioning of the receptors to a normal level takes place. This sequence of events may lead to a condition of relative adrenergic hypersensitivity.
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PMID:The beta-adrenergic system in man: physiological and pathophysiological response. Regulation of receptor density and functioning. 197 55

46-year-old male patient was born in Niigata Prefecture and thereafter lived in Tokyo. In late January 1985, he noticed swelling of the bilateral inguinal lymph-nodes followed by fever and lumbago. In February, he consulted a local doctor and hepatosplenomegaly, marked leukocytosis and renal dysfunction were pointed out and he was referred to our hospital on February 22nd. The clinical laboratory data on admission were as follows; WBC 23,200/microliter, serum-Ca 18.4 mg/dl, BUN 85.3 mg/dl, creatinine 5.4 mg/dl, antibody to ATLV x160. ATL was diagnosed by biopsy of lymph nodes and examinations of peripheral blood and bone marrow hemogram. Remission was achieved in March by the treatment with adriacin. Renal failure and hypercalcemia also improved. However his respiratory dysfunction gradually worsened. The chest radiographies++ showed pulmonary edema, although there was no clinical evidence of heart failure. When his condition became stable, TBLB was performed and revealed extensive deposition of calcium along alveolar septae, suggesting that pulmonary edema was induced by the metastatic calcification of the lung. After the second treatment for ATL, he died of pneumonia. The autopsy showed calcium deposition not only in the lung but in pyramids of the kidney and in sub-serous layer of the small intestine. There was no tumor cell invasion into the bone or parathyroid gland. High urinary c-AMP together with normal levels of PTH suggested that the hypercalcemia in this case was induced by PTH-related protein. It was concluded that careful treatment for hypercalcemia is important as regards the occurrence of pulmonary edema.
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PMID:[An autopsy case of adult T-cell leukemia complicated with metastatic calcification of the lung]. 204 Dec 50

Theoretically, there are two reasons for using the association of dobutamine and enoximone in patients with acute cardiac failure; the powerful vasodilator effect of enoximone and the different biochemical actions of the two drugs on the myocardial fibre affecting the production (dobutamine) or the degradation (enoximone) of cyclic AMP. The combined effects of beta adrenergic agonists and phosphodiesterase III inhibitors in vitro and in vivo have been previously reported. An increased contractile response to dobutamine has been demonstrated with enoximone on isolated human ventricle obtained during cardiac transplantation. We confirmed the additive effect of dobutamine (5 to 10 micrograms/kg/min) and enoximone (1 mg/kg/bolus IV) in 8 patients with acute cardiac failure with each molecule used alone. Mild changes in heart rate (+19 bpm) and in systolic blood pressure (-3 mmHg) were observed simultaneously. The absence of an increase in SvO2 compared to the use of each molecule in monotherapy is probably related to a tendency to increase myocardial oxygen consumption which may be potentially deleterious in terms of gas exchange. Having demonstrated the additive effects of the association of dobutamine and enoximone, there is probably a place for this therapeutic association in the management of acute cardiac failure. However, the potential risk of inducing an atrial and/or ventricular tachyarrhythmia and the consequences of lowering ventricular filling pressures and systemic vascular resistances should be born in mind; when using this therapeutic association, the authors suggest starting treatment with low doses of dobutamine (5/kg/min) and enoximone (0.5 - 1 mg/kg) with haemodynamic control and steadily increasing the doses, depending on the results obtained.
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PMID:[Role of the enoximone-dobutamine combination in the treatment of congestive cardiac insufficiency]. 214 32

Enoximone belongs to a new class of noncatecholamine-positive inotropes, which selectively inhibit phosphodiesterase type III and increase cyclic AMP (cAMP). This study was performed in 30 coronary artery surgery patients with impaired myocardial function (ejection fraction [EF] less than 50%). The study's two purposes were to investigate the hemodynamic effects of enoximone, 0.5 mg/kg, administered following induction of anesthesia (phase I), and to assess whether enoximone can potentiate the actions of sympathomimetic agents during weaning from cardiopulmonary bypass (CPB) (phase II). Starting with already reduced hemodynamics, induction of anesthesia led to a further deterioration of blood pressure and cardiac output (CO). Administration of enoximone produced a significant increase in cardiac index (CI) (+47%), whereas pulmonary capillary wedge pressure (PCWP) (-37%), pulmonary artery pressure (PAP) (-17%), and systemic vascular resistance (SVR) (-17%) were significantly reduced. Heart rate (HR) was not increased, and no dysrhythmias occurred during the investigation. The hemodynamic effects were maintained for 30 minutes until the start of the operation. In phase II, where weaning from CPB was not possible without pharmacological support, either enoximone (0.5 mg/kg) + epinephrine (0.1 micrograms/kg/min) or only epinephrine (same dosage) was randomly selected. Weaning was successful in both groups, but the combined therapy produced a larger increase in cl and a more pronounced decrease of the elevated filling pressure (PCWP). PAP was not changed in the combined therapy group, but increased in the patients receiving epinephrine alone. It is concluded that enoximone has beneficial hemodynamic effects in the perioperative period, and that potentiation of the effects of epinephrine in severe heart failure may be one of the drug's most useful features.
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PMID:Enoximone treatment of impaired myocardial function during cardiac surgery: combined effects with epinephrine. 215 89

Calcium ions are important in many aspects of normal cardiac function as well as in the response to certain pathologic states. The contribution that myocardial calcium influx makes to the cardiac action potential and the pharmacologic efficacy of compounds designated as calcium channel blockers is examined with respect to current knowledge regarding the structure and characteristics of cardiac sarcolemmal calcium channels. Once intracellular, calcium provides the link between cardiac electrical activity and actual mechanical shortening of cardiomyocytes through a complex interaction of regulatory and structural contractile proteins. This is followed by calcium clearance from the cytosol; the mechanisms by which this occurs are manipulated by drugs such as the digitalis glycosides to enhance myocardial contractility. The importance of intracellular 'second messengers' (eg, cyclic AMP) in constituting a final common pathway for the effects of certain cardiotonic agents is defined. The significance of abnormal calcium homeostasis under conditions of heart failure, myocardial infarction, ventricular fibrillation and cardiomyopathy is examined. The role of calcium in the mediation of myocardial damage under conditions of ischemia and secondary to a phenomenon known as 'the calcium paradox' is discussed. The finding that neonatal hearts are more vulnerable to ischemic contracture than adult hearts may be partially explained by differences between neonatal and adult myocardial calcium handling. Understanding of the interactions that exist between the calcium ion and the cardiomyocyte requires a sound knowledge of this essential partnership by both the physiologist and the practising physician.
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PMID:Calcium and the heart: an essential partnership. 217 38

Low cardiac output in acute heart failure can result in a functional impairment of organs, when tissue hypoxia occurs and cardiogenic shock develops. To restore cardiac output, various forms of therapy can be considered. Fluid replacement is sometimes beneficial in acute situations where oedema can reduce effective plasma volume. Vasodilators are often contra-indicated in shock, when arterial pressure is usually low. Inotropic therapy consists primarily of the administration of adrenergic agents. Dopamine and noradrenaline can be indicated in severe hypotension, to maintain coronary perfusion. Dobutamine is the catecholamine of choice to increase myocardial contractility. However, decreased responsiveness of the myocardial receptors to adrenergic stimulation rapidly becomes an important limitation. Phosphodiesterase inhibitors represent an interesting option to increase contractility, also by increasing cyclic AMP levels in the myocardium. In this respect, the combination of phosphodiesterase inhibitors with adrenergic agents is attractive. The additional vasodilatory properties of these agents can contribute to the increase in cardiac output with limited risk of further reduction in arterial pressure. In 13 patients with cardiogenic shock persisting despite the use of adrenergic agents, the addition of enoximone, 0.5 mg/kg, resulted in significant increases in cardiac index and stroke volume index and a significant decrease in pulmonary artery balloon occlusion pressure without consistent change in mean arterial pressure. In 8 patients, a second infusion of 0.5 g/kg amplified these effects. All but one of these patients survived the episode of cardiogenic shock, and 5 patients were discharged alive. In some cases, even lower doses of enoximone resulted in dramatic increases in cardiac output and oxygen transport in patients already treated with dobutamine with limited success.
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PMID:The role of enoximone in the treatment of cardiogenic shock. 217 30

The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure.
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PMID:Inotropic effects of angiotensin II on human cardiac muscle in vitro. 224 22

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