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

A long-term follow-up study was performed for 110 patients with idiopathic dilated cardiomyopathy (DCM) for 34 +/- 12 months (range 3-122 months). Thirteen patients died of heart failure, 15 of sudden death and one of non-cardiac death. The 3- and 5-year survival rates were 78 and 62%, respectively. The important factors in predicting the 3-year survival rate were left ventricular end-diastolic volume index (LVEDVI > or = 150 ml/m2 = 66%, < 150 ml/m2 = 93%, p < 0.01), myocardial cell diameter (> 25 microns = 42%, < or = 25 microns = 87%, p < 0.05) and sustained ventricular tachycardia (VT present = 32%, absent = 85%, p < 0.01). In a prospective study, 26 patients with DCM were given a beta 1-partial agonist, xamoterol (200 mg daily) and were followed for 35 +/- 15 months (6-53 months). The cardiothoracic ratio, left ventricular end-diastolic dimension and exercise heart rate decreased, and the exercise duration, fractional shortening and ejection fraction increased after xamoterol therapy. The 3-year survival rate was 83%. These results suggest that the important factors in predicting the survival rate of DCM patients were LVEDVI, myocardial cell diameter and the occurrence of VT. Adjunctive xamoterol therapy in DCM had a beneficial effect on hemodynamics and symptoms.
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PMID:Risk factors and the effects of xamoterol in idiopathic dilated cardiomyopathy. 133

The prognosis of heart failure patients is poor and as many as half of the deaths are sudden and thereby presumably attributable to arrhythmias. In the present study the effect of traditional therapy of mild heart failure with digoxin on arrhythmias was compared with the effect of xamoterol, a cardioselective beta 1 partial agonist, which has in addition beta-blocking properties at higher levels of sympathetic tone. Fifteen patients (NYHA class II-III) were included in the study. After a two-week baseline period they were randomized to digoxin or xamoterol for four weeks followed by a two-week washout and another four weeks of crossover therapy. Heart rate, blood pressure, and the number of complex ventricular premature beats remained essentially unchanged with digoxin. With xamoterol heart rate increased from 86 to 93 (ns) but was significantly higher during the night in comparison with digoxin. The number of ventricular premature beats decreased from 186 +/- 317 to 110 +/- 137 and increased to 130 +/- 175 after treatment. The number of runs decreased from 11 +/- 35 to 2.7 +/- 5 and increased to 5.6 +/- 9 after therapy. In conclusion, no significant effect of digoxin or xamoterol on ventricular arrhythmias was found. However, xamoterol showed a tendency to reduce simple and complex ventricular arrhythmias in patients with mild to moderate heart failure.
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PMID:Comparative effects of digoxin and xamoterol on arrhythmias in patients with mild to moderate heart failure. 134 3

1. alpha 1-Adrenoceptor (phenylephrine in the presence of propranolol) and beta 2-adrenoceptor (fenoterol)-mediated positive inotropic effects were investigated in human ventricular preparations isolated from five non-failing (prospective organ donors) and from eight explanted failing hearts with end-stage idiopathic dilative cardiomyopathy (NYHA IV). 2. For comparison, the nonselective beta-adrenoceptor agonist isoprenaline, the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX), the cardiac glycoside dihydroouabain, and calcium were studied. 3. Furthermore, the influence of IBMX on adenosine 3':5'-cyclic monophosphate (cyclic AMP) PDE activity as well as total beta-adrenoceptor density, beta 1- and beta 2-adrenoceptor subtype distribution, and alpha 1-adrenoceptor density were compared in nonfailing and failing human heart preparations. The radioligands (-)-[125I]-iodocyanopindolol for beta-adrenoceptor binding and [3H]-prazosin for alpha 1-adrenoceptor binding were used. 4. The inotropic responses to calcium and dihydroouabain in failing human hearts were unchanged, whereas the maximal alpha 1- and beta 2-adrenoceptor-mediated positive inotropic effects were greatly reduced. The inotropic effects of the other cyclic AMP increasing compounds, i.e. isoprenaline and IBMX, were also reduced to about 60% of the effects observed in nonfailing controls. The potency of these compounds was decreased by factors 4-10. 5. The basal PDE activity and the PDE inhibition by IBMX were similar in nonfailing and failing preparations. 6. The total beta-adrenoceptor density in nonfailing hearts was about 70 fmol mg-1 protein. In failing hearts the total number of beta-adrenoceptors was markedly reduced by about 60%. The betal/beta2-adrenoceptor ratio was shifted from about 80/20% in nonfailing to approximately 60/40% in failing hearts which was due to a selective reduction of beta1-adrenoceptors. The beta2-adrenoceptor population remaining unchanged. alpha-Adrenoceptor density was increased from about 4 fmol mg-' protein in nonfailing to 10 fmol mgprotein in failing hearts.7. Changes in PDE activity and adrenoceptor downregulation cannot completely explain the reduced positive inotropic effects of alpha 1- and beta 2-adrenoceptor agonists in failing human hearts. This supports the hypothesis that impairment of other processes such as the coupling between receptor and effector system, i.e. the respective G-proteins, are equally important in end-stage heart failure.
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PMID:Reduced alpha 1- and beta 2-adrenoceptor-mediated positive inotropic effects in human end-stage heart failure. 134 46

Carvedilol, a new beta-blocker with vasodilating properties due to alpha 1-blockade, was investigated in preparations of human ventricular myocardium. Carvedilol demonstrated a high affinity and is a slightly beta 1-selective competitive beta-blocking agent, with a KD for beta 1-receptors of approximately 4-5 nM and a mild selectivity for beta 1 vs. beta 2 receptors of 6- to 39-fold, depending on the method employed to assess subtype potency. In addition, carvedilol was also a potent alpha 1-blocking agent, with a beta 1:alpha 1 blocking relative potency of 1.7-fold. In human lymphocytes containing beta 2-receptors and in human myocardial membranes containing both beta 1- and beta 2-receptors carvedilol exhibited the unique property of guanine nucleotide modulatable binding. Despite this, no intrinsic sympathomimetic activity of carvedilol was detected in preparations of isolated human heart or in myocardial membranes. Vasodilation related to alpha 1-blockade and the lack of intrinsic activity should translate into improved tolerability and good efficacy in the treatment of heart failure.
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PMID:Effects of carvedilol on adrenergic receptor pharmacology in human ventricular myocardium and lymphocytes. 135 Apr 78

Esmolol is a specific beta 1-blocker; it is hydrosoluble, without intrinsic sympathetic activity. Distribution half-life is 2 minutes and elimination half-life 9 minutes. Esmolol is hydrolyzed by the blood esterases. Its indications are all those where inotropism and heart rate must be briefly and specifically diminished using a titration technique: 1) In patients with coronary artery disease, or poor cerebral compliance, just before a strong nociceptive stimulus like intubation, extubation, skin incision, etc. 2) In patients with coronary artery disease, to decrease oxygen consumption by the myocardium. 3) In patients with hypertensive episodes per and post-operatively, especially in vascular surgery and neurosurgery. 4) In cardiac insufficiency due to obstructive cardiomyopathy. 5) In patients with specific cardiac rhythm problems. 6) In all patients where propranolol is indicated bu cannot de administered due to its long duration of action. Esmolol has to be given either as a mini-infusion at a rate of 300-600 micrograms/kg/min for the first 1-2 minutes followed by 200-300 micrograms/Kg/min or as a bolus (just before a nociceptive stimulus) 1-3 mg/kg. When using esmolol, it is important to set limits within which heart rate and blood pressure must remain. Over-dosage can occur easily but can be avoided without difficulty.
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PMID:[Characteristics and clinical use of esmolol]. 135 93

Catecholamines acting through beta 1- and beta 2-adrenergic receptors cause positive inotropic and chronotropic effects in the human heart. However, recent evidence suggests that in the human heart other receptor systems can also affect heart rate and contractility. Positive inotropic effects can be mediated by receptor systems acting through accumulation of intracellular cyclic adenosine monophosphate (cAMP; Gs-protein-coupled receptors such as 5-hydroxytryptamine(5-HT)4-like, histamine H2, and vasoactive intestinal peptide) or by receptor systems acting independently of cAMP, possibly through the phospholipase C/diacylglycerol/inositol-1,4,5-trisphophate pathway (such as alpha 1-adrenergic, angiotensin II, and endothelin). In the nonfailing human heart, activation of all these receptor systems induces only submaximal positive inotropic effects compared with those caused by beta-adrenergic receptor stimulation, indicating that in humans the cardiac beta-adrenergic receptor/Gs-protein/adenylate cyclase pathway is the most powerful mechanism to increase heart rate and contractility. However, the human heart contains only a few spare receptors for beta-adrenergic receptor-mediated positive inotropic effects and nearly all beta-adrenergic receptors are needed to cause maximal inotropic effects. Thus any decrease in the number of beta-adrenergic receptors will automatically lead to a reduction in functional responsiveness of beta-adrenergic receptors. In chronic heart failure the number and responsiveness of cardiac beta-adrenergic receptors are reduced, presumably because of the enhanced sympathetic drive to the heart and hence endogenous down-regulation by an elevated release of (cardiac-derived) norepinephrine, and this loss in cardiac beta-adrenergic receptor function is strongly related to the severity of the disease. However, beta 1- and beta 2-adrenergic receptors are differentially changed in different forms of heart failure. In dilated cardiomyopathy and possibly in aortic valve disease the number of cardiac beta 1-adrenergic receptors is selectively reduced without alteration in the number of beta 2-adrenergic receptors (although beta 2-adrenergic receptors become somewhat uncoupled). In ischemic cardiomyopathy, mitral valve disease, and possibly tetralogy of Fallot, the number of both beta 1- and beta 2-adrenergic receptors is concomitantly decreased. Because of the lack of a substantial receptor reserve, such a decrease in the number of beta-adrenergic receptors is accompanied by reduced inotropic and chronotropic responses to beta-adrenergic receptor stimulation in vitro and in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Receptor systems affecting force of contraction in the human heart and their alterations in chronic heart failure. 135 62

A review over adrenergic transmembrane signalling in human heart muscle cells, changes in this signalling in patients with heart failure and the influence of medical treatment of heart failure, is presented. In heart failure, the myocardial contractibility is decreased, although the plasma level of catecholamines is elevated. This can be due to changes in the transmembrane signalling. In heart failure, the numbers of beta-receptors are decreased, the amount of Gs-protein is probably unchanged and the amount of Gi-protein is probably increased. Changes in signalling are described in more detail in patients with heart failure based on idiopathic dilated cardiomyopathy (DCM), where a selective down regulation of beta 1-receptors is seen. In heart failure of other origin, there is probably a concomitant reduction in beta 1- and beta 2-receptors. The selective regulation in patients with DCM, can be based on autoantibodies. A 30% reduction in maximal response on selective beta 2 stimulation is additionally seen in patients with DCM, probably based on an increase in the amount of Gi-protein. beta-antagonists increase and beta-agonists decrease the numbers of beta-receptors. The regulation is selective when selective antagonists and agonists are used, and nonselective when nonselective drugs are used. How other drugs affect the transmembrane signalling is still to be elucidated.
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PMID:[Adrenergic signal transduction in heart failure]. 135 1

Xamoterol acts as a beta 1-adrenoceptor agonist at low sympathetic activity and as an antagonist at high activity. Although its long-term efficacy has been proven in patients with mild to moderate heart failure, it remains unclear which effect, agonism or antagonism, accounts for its long-term activity. To clarify the effect of xamoterol on cardiac sympathetic activity in daily life, 24-h R-R interval histograms were obtained during administration of xamoterol 100 mg b.d. for 1 week to 10 patients with mild to moderate heart failure. Eight normal subjects were also studied as controls. To examine the relation between the effect of xamoterol and sympathetic activity, plasma noradrenaline (NA) levels were measured under 5 graded conditions simulating daily living. Xamoterol administration significantly decreased the standard deviation of the R-R interval, both in patients with heart failure and in normal subjects. The mean R-R interval, however, was increased in patients with heart failure, relative to normal subjects. In both groups, the R-R interval histograms had two peaks, i.e. a short daytime peak and a long night-time peak. Xamoterol decreased the median of the night-time peak without changing the daytime peak in normal subjects. In contrast, it increased the median of the daytime peak without producing a significant change in the night-time peak in patients with heart failure. Levels of plasma NA were significantly higher in patients than in normal subjects under all conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Predominant beta-adrenoceptor blocking effect of xamoterol averaged over the day in patients with mild to moderate heart failure: insight into the mechanism of its long-term clinical efficacy. 136 83

Dopexamine hydrochloride is a synthetic catecholamine proposed for the short-term treatment of heart failure and postoperative low cardiac output. The pharmacological profile and anatomical localization of dopexamine binding were investigated in sections of right and left ventricle using [3H]-dopexamine and ligand techniques associated with light microscope autoradiography. Its effects on the 3-5-cyclic adenosine monophosphate (cAMP) generating system in membrane particles of the human right or left ventricle were also studied. [3H]-Dopexamine was specifically bound to sections of human right or left ventricle. The binding was time-, temperature- and concentration-dependent and was dissociable. The apparent equilibrium constant of dissociation was 3.5 nM. A decreased [3H]-dopexamine binding capacity from the base to the apex and ventricles was noticeable. The pharmacological profile of [3H]-dopexamine binding to sections of right or left ventricle was consistent with the labelling of both beta 2-adrenoceptors and dopamine DA-2 receptors. The most potent displacer of [3H]-dopexamine was the beta 2-adrenoceptor antagonist ICI 118,551 followed by dopamine, noradrenaline and domperidone. The beta 1-adrenoceptor antagonist metoprolol or the dopamine DA-1 receptor antagonist SCH 23390 were ineffective as displacers of [3H]-dopexamine binding. Light microscope autoradiography revealed the localization of [3H]-dopexamine binding sites within the wall of the human right and left ventricle. The density of silver grains was slightly higher in the right than in the left ventricle and showed a uniform transmural distribution across the ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dopexamine hydrochloride in the human heart: receptor binding and effects on cAMP generation. 136 32

Substantial evidence has accumulated that in the human heart both beta 1- and beta 2-adrenoceptors coexist. As a rule, the amount of beta 2-adrenoceptors is higher in the atria (about 30% of the total beta-adrenoceptor population) than in the ventricular myocardium (about 20%). Both beta 1- and beta 2-adrenoceptors couple to adenylate cyclase and mediate positive inotropic effects of isoprenaline and adrenaline on isolated, electrically driven cardiac preparations. In the atria, stimulation of both beta 1- and beta 2-adrenoceptors causes maximal increases in contractile force; in the ventricular myocardium, however, only beta 1-adrenoceptor stimulation maximally increases contractile force, whereas beta 2-adrenoceptor stimulation evokes only submaximal increases. On the other hand, noradrenaline induces its positive inotropic effect on atrial and ventricular preparations solely via beta 1-adrenoceptor stimulation. Because nordadrenaline is the main transmitter of the human sympathetic nervous system, this indicates that under normal physiological conditions, the heart rate and contractility are under the control of cardiac beta 1-adrenoceptors, whereas cardiac beta 2-adrenoceptors play only a minor role, if at all. However, in situations of stress, when large amounts of adrenaline (acting at both beta 1- and beta 2-adrenoceptors with the same affinity) are released from the adrenal medulla, activation of cardiac beta 2-adrenoceptors may contribute to an additional increase in heart rate and/or contractility. In chronic heart failure, cardiac beta-adrenoceptor function decreases (presumably due to endogenous "downregulation" by the elevated catecholamines) and this decrease is related to the severity of the disease (judged clinically by NYHA functional class).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Importance of beta 2-adrenergic receptors in heart failure]. 136 62


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