Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587), a beta 1-adrenoceptor partial agonist, improves both systolic and diastolic function in heart failure patients. 2. Double-blind, randomised studies comparing xamoterol with placebo showed that the beneficial haemodynamic effects of xamoterol produced significant improvements in exercise capacity and symptoms in patients with mild to moderate heart failure. These studies formed the basis for a large European multicentre study programme which recruited over 1000 patients, randomised to xamoterol (200 mg twice daily, n = 617), digoxin (0.125 mg twice daily, n = 135) or placebo (n = 300) for 3 months. 3. Efficacy was assessed by measuring exercise capacity and symptoms. The xamoterol group improved exercise capacity by 37% compared with an 18% improvement in the placebo group. Differences in the symptom scores measured by visual analogue scales and Likert scores indicated significant improvements by xamoterol in the cardinal symptoms of heart failure, dyspnoea and fatigue. 4. Analyses of data from subsets of patients in the study showed that elderly patients, patients on no other heart failure therapy and patients with cardiomegaly all had similar improvements in exercise and symptoms to those seen in the whole study population. In the subset which included digoxin treatment, xamoterol produced significantly greater improvements in exercise capacity than digoxin (33% vs 17%, P less than 0.05) and was associated with fewer side-effects. 5. Xamoterol is therefore a promising addition to heart failure therapies currently available.
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PMID:Xamoterol, a beta 1-adrenoceptor partial agonist: review of the clinical efficacy in heart failure. 257 51

1. Cardiac failure is a clinical syndrome of symptoms and signs, which can be confirmed by imaging or invasive haemodynamic techniques. It may be caused by systolic or diastolic dysfunction, but systolic dysfunction rarely occurs alone. It is important to ascertain the degree to which each contributes, and the precise aetiology of the condition, particularly in relation to surgically correctable lesions. 2. Non-pharmacological approaches including weight loss, salt restriction and lifestyle changes may be beneficial in some patients, and diuretics, which reduce the load on the heart, are the traditional baseline therapy. 3. Digitalis has been used where problems with contractility predominate, but its beneficial effect has been disputed, and expectations of improvement in patients in sinus rhythm should not be too high. 4. Vasodilators have been considered as the next line of treatment. Arteriolar dilators tend to increase cardiac output, but have little effect on pulmonary artery wedge pressure, and venodilators tend to have the opposite effect. Probably both actions are necessary and angiotensin converting enzyme (ACE) inhibitors, which have both, have proved effective in terms of symptoms and survival. 5. Various other inotropic agents have been tried. Phosphodiesterase inhibitors improve exercise tolerance, but may increase the probability of serious arrhythmias, already a significant cause of sudden death. beta 1-partial adrenoceptor agonists such as xamoterol have shown some promise, and anti-arrhythmic therapy has also been considered. 6. Drugs which prevent progression of myocardial damage would prove a great advance, and beta-adrenoceptor antagonists and calcium channel blockers appear to have considerable potential in this area.
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PMID:Treatment of congestive heart failure--state of the art and future trends. 257 53

1. Although heart failure is commonly associated with depressed systolic function, there is increasing evidence that impaired diastolic performance is also universally present and might be a key determinant of symptoms, physical capacity and even survival in some subsets of patients. 2. Reduced diastolic distensibility increases cardiac filling pressure not only at rest, but even more during exercise when diastolic filling time is reduced. The increases in filling pressure and diastolic wall stress lead to pulmonary congestion and subendocardial ischaemia, it also triggers myocardial hypertrophy and a detrimental remodelling of the ventricular cavity. Perhaps even more importantly, impaired ventricular distensibility limits the use of the Frank-Starling mechanism, impairing systolic pump function and cardiac output adaptation during exercise. Therapies able to improve the distensibility of the ventricle are, therefore, desirable in heart failure. 3. Nitrates, angiotensin converting enzyme (ACE) inhibitors and diuretics may indirectly increase left ventricular chamber compliance by their effects on the right side of the heart. Cardiac glycosides do not improve myocardial relaxation and may even cause diastolic contracture at toxic doses. The new beta 1-adrenoceptor partial agonist, xamoterol, on the other hand, consistently lowers left ventricular filling pressure at rest and during exercise, and produces an increase in left ventricular dynamic compliance through the direct lusitropic effect of beta 1-adrenoceptor stimulation. These beneficial effects are maintained during prolonged therapy and also appear sufficient to slow the remodelling of the ventricular cavity. The improvement in symptoms and in exercise tolerance observed during xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587) therapy might, therefore, be related to the improvement in left ventricular diastolic distensibility induced by this drug.
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PMID:Focus on diastolic dysfunction: a new approach to heart failure therapy. 257 54

1. Xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587) is a beta 1-adrenoceptor partial agonist which, unlike full beta-adrenoceptor agonists, does not down-regulate beta-adrenoceptors in the rat ventricle during chronic administration. 2. Improvements in myocardial performance have been demonstrated following acute administration of xamoterol to patients with mild or moderate heart failure, and these are sustained during at least 1 year of continued treatment. 3. Exercise duration is increased by xamoterol in patients with left ventricular dysfunction and benefit is still apparent after at least 1 year of therapy. 4. Despite sustained cardiac stimulation, xamoterol does not appear to affect adversely mortality in patients with mild or moderate heart failure. 5. Few adverse events directly attributable to xamoterol were reported during 3 month efficacy studies in more than 600 patients, and the laboratory safety profile over 1 year of treatment is good. 6. Xamoterol is a promising, well-tolerated addition to established therapies for chronic mild or moderate heart failure.
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PMID:Long-term studies with xamoterol in heart failure. 257 55

Impaired left ventricular diastolic dysfunction is common in patients with ischaemic heart failure. The beta 1-adrenoceptor partial agonist xamoterol was compared with pindolol, a beta-adrenoceptor blocker with intrinsic sympathomimetic activity, in a haemodynamic study in 17 patients with ischaemic heart disease. Pindolol caused left ventricular end-diastolic pressure, wall stress and T1 to rise, whereas xamoterol produced improvements in all three parameters. These results suggest that xamoterol may be of greater benefit to patients in heart failure.
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PMID:Contrasting effects of single doses of pindolol and xamoterol on left ventricular diastolic function. 257 64

The stimulant effects of adrenaline and noradrenaline on contractile force and adenylate cyclase, mediated through beta 1 and beta 2-adrenoceptors, are analysed in isolated atrial and ventricular myocardium of man. The tissues were obtained from patients without advanced heart failure undergoing heart surgery. Usually, both adrenaline and noradrenaline stimulated adenylate cyclase predominantly through ventricular and atrial beta 2-adrenoceptors. Because the relative density of beta 2-adrenoceptors is usually smaller than that of beta 1-adrenoceptors, stimulation of one beta 2-adrenoceptor leads to the production of up to 10 times more cyclic AMP molecules than does stimulation of one beta 1-adrenoceptor. Adrenaline and noradrenaline maximally enhance contractile force through both atrial and ventricular beta 1-adrenoceptors. Adrenaline can also maximally enhance contractile force through atrial beta 2-adrenoceptors. In the ventricle, adrenaline increases force via beta 2-adrenoceptors by up to 60% of its maximal beta 1 response. Noradrenaline can increase atrial and ventricular contractile force through beta 2-adrenoceptors but only at high concentrations. Unexpectedly, in atria from patients treated with the beta 1-selective antagonist atenolol, contractile responses to adrenaline are markedly and selectively augmented through activation of beta 2-adrenoceptors. In atria from atenolol-treated patients equi-inotropic concentrations of adrenaline and noradrenaline acting through beta 2 and beta 1-adrenoceptors, respectively, cause similar increases of cyclic AMP and of cyclic AMP-dependent protein kinase activity.
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PMID:A comparison of the effects of adrenaline and noradrenaline on human heart: the role of beta 1- and beta 2-adrenoceptors in the stimulation of adenylate cyclase and contractile force. 257 19

The subtypes of alpha- and beta- and dopaminergic receptors have been identified along with specific agonists and antagonists. The effects of alpha-receptor agonists on haemodynamics results from the interaction of relative changes in vascular tone and increase in myocardial contractility. Predominantly, beta 1 agonists improve cardiac performance by increasing contractility which is usually accompanied by increased myocardial oxygen consumption. Dopaminergic receptor agonists improve left ventricular function primarily by reduction in systemic vascular resistance usually without a change in myocardial oxygen consumption. beta 2-receptor agonists improve cardiac function both by increasing contractility and by peripheral vasodilation usually without an increase in metabolic cost. The effects of various adrenoreceptor agonists such as dobutamine, dopamine, prenalterol, levodopa and dopexamine on systemic and coronary haemodynamics and on myocardial energetics in heart failure are reviewed.
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PMID:Central and peripheral adrenergic receptor agonists in heart failure. 257 21

Myocardial oxygen uptake and an index of mechanical left ventricular efficiency were determined in basal conditions or during prolonged therapy with the new beta 1-adrenoceptor partial agonist xamoterol in 16 patients with mild to moderate ischemic heart failure. During xamoterol therapy, left ventricular end-diastolic pressure decreased from 24.4 +/- 6.5 to 17.8 +/- 8.6 mm Hg (P less than 0.01) and the isovolumic index of inotropic state (dP/dt)/DP40 increased by 14% (P less than 0.01). The heart rate increased slightly and the mean systolic and peak systolic wall stress also tended to increase (+ 7%; NS) but myocardial oxygen uptake (14.1 vs 14.7 ml/min; NS) and the index of efficiency (8.77 +/- 3.44 to 8.82 +/- 4.27; NS) were not significantly modified. In conclusion, prolonged therapy with xamoterol was not accompanied by a deterioration in the mechanical efficiency of the ventricle, even in patients with ischemic heart disease.
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PMID:Effects of long-term xamoterol therapy on the left ventricular mechanical efficiency in patients with ischemic heart disease. 257 38

The failing heart operates with an abnormal combination of heart rate, stroke volume, and enddiastolic volume. This mismatch becomes more evident during exercise of patients with heart failure, when an increase in cardiac output is achieved with higher heart rate, a lower stroke volume and a higher enddiastolic volume. Using the beta 1-adrenoceptor partial agonist xamoterol which lacks beta 2-adrenoceptor agonism the response of the heart to sympathetic stimulation can be modulated. At rest and low levels of exercise xamoterol provides an inotropic support of the heart, whereas it reduces inappropriate tachycardia at higher levels. Thereby, xamoterol tends to normalize the balance of the inotropic and chronotropic control of the failing heart, because cardiac output is increased with a more normal combination of heart rate, stroke volume, and filling pressure. The beneficial effects of xamoterol are discussed as being especially important for failing ischemic hearts, because the balance between energy supply and energy demand may be improved by xamoterol.
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PMID:Modulation of the autonomic control of the failing heart. 257 39

The clinical efficacy of xamoterol, alpha beta 1-adrenoceptor partial agonist, was determined in a multicentre double-blind, randomized, parallel group study of 240 patients with mild to moderate heart failure. At entry, 62% of patients were receiving diuretics (thiazides, or loop diuretics at a dose no greater than the equivalent of 80 mg of frusemide); 32% were taking nitrate formulations and 14% digoxin for control of atrial fibrillation. Assessments were carried out after a 1-week placebo run-in and after 3 months of treatment with either xamoterol or placebo. 198 patients completed the study of whom 186 had valid exercise tests. Mean exercise duration increased by 7% after placebo and by 19% after xamoterol during a progressive treadmill exercise protocol. Xamoterol significantly reduced peak exercise heart rate compared with placebo. Subjectively, there was improvement in breathlessness on the visual analogue scale after treatment with xamoterol compared with placebo, but no change in fatigue. We conclude that xamoterol produces sustained improvement in symptoms and exercise duration in mild to moderate heart failure.
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PMID:Clinical efficacy of xamoterol, a beta 1-adrenoceptor partial agonist, in mild to moderate heart failure. U.K. Xamoterol Study Group. 257 8


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