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)

In patients with chronic heart failure cardiac beta-1 adrenoceptors are reduced, whereas beta-2 adrenoceptor changes vary depending on the etiology of the disease. Beta Adrenoceptor agonists can be used for short-term inotropic support in chronic heart failure; their clinical efficacy might depend on which beta adrenoceptor subtype(s) mediates their positive inotropic effect. Thus, the beta adrenoceptor subtype(s) involved in the positive inotropic effects of clinically used beta adrenoceptor agonists was characterized on isolated electrically driven human right atria by the use of the selective beta-1 adrenoceptor antagonist CGP 20712 A (300 nmol/l) and/or the selective beta-2 adrenoceptor antagonist ICI 118,551 (30 nmol/l). Epinine evoked positive inotropic effects through stimulation of beta-1 and beta-2 adrenoceptors to about the same degree, whereas dobutamine acted mainly at beta-1 adrenoceptors but had a significant beta-2 adrenoceptor component. Both agonists were full agonists causing the same maximum increase in contractile force (Emax) as did isoprenaline or Ca++ (Emax = 1.0). In contrast, denopamine was a partial selective beta-1 adrenoceptor agonist (Emax = 0.75-0.85). Dopamine was in the presence of uptake1-blockade (by 5 mumol/l phenoxybenzamine) a partial agonist (Emax = 0.60-0.70) acting selectively at beta-1 adrenoceptors; in the absence of uptake1-blockade, however, dopamine was a full agonist, indicating that part of its positive inotropic effect is indirect via the release of endogenous noradrenaline. Xamoterol did not exert positive inotropic effects, but concentration-dependently slightly decreased basal force of contraction.
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PMID:Characterization of the beta adrenoceptor subtype(s) mediating the positive inotropic effects of epinine, dopamine, dobutamine, denopamine and xamoterol in isolated human right atrium. 135 51

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

Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure. 167 87

The double-blind, placebo-controlled, multinational trial Xamoterol in Severe Heart Failure randomized 290 patients treated with captopril and 217 treated with enalapril to xamoterol or placebo. At the end of the 100-day follow-up period, the cumulative probability of survival in patients with coronary artery disease or with dilated cardiomyopathy decreased in the captopril group (90.3%) when compared with the enalapril group (97.2%). The excess mortality in the captopril group could not be related to the indexes of the severity of heart failure, such as baseline exercise duration, functional class, cardiothoracic ratio, ejection fraction or dose of diuretic drugs. Furthermore, the excess in mortality was seen in all subsets of patients examined as well as across countries. Examination of the dosing regimen used, however, suggests that insufficient daily dosage of captopril or the inadequate schedule of administration, or both, might be responsible for different degrees of angiotensin-converting enzyme inhibition between the enalapril and captopril groups and hence for the difference in mortality. It is important in future clinical trials to determine to what extent complete circadian angiotensin-converting enzyme inhibition is necessary to provide the full benefit of this therapy in heart failure.
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PMID:Difference in mortality between patients treated with captopril or enalapril in the Xamoterol in Severe Heart Failure Study. 205 42

Xamoterol is a novel partial agonist of beta 1 adrenoceptors that reduces myocardial ischaemia and improves ventricular function in patients with mild to moderate heart failure. In a double blind, randomised, placebo controlled study, the effects of xamoterol given in a dose of 200 mg twice daily were studied in 51 consecutive patients with acute myocardial infarction, including 17 receiving diuretics for left ventricular failure. Treatment was started on the third day of admission and continued for 7 days. Blood pressure was recorded at 0900 daily, and 24 hour ambulatory electrocardiogram monitoring was commenced at this time on days 1 (pre-treatment), 4, 6 and 9 of admission. Additional drug therapy was recorded daily throughout the study. One patient died prior to randomisation and three were withdrawn (1 placebo, 2 xamoterol) with ventricular arrhythmias and/or disturbances of conduction. Compared to placebo, xamoterol had no effect on the rate of ventricular premature beats or ventricular tachycardia. Xamoterol increased nocturnal heart rate (0000-0600 hrs 79 +/- 2; placebo 72 +/- beats/min; P less than 0.03) but did not change blood pressure. Three patients receiving xamoterol, and 7 on placebo, required new (after randomisation) antianginal therapy. One patient treated with placebo developed new heart failure. These results show that xamoterol can be administered safely to selected patients following myocardial infarction, including those treated for mild heart failure.
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PMID:Effects of xamoterol in acute myocardial infarction: blood pressure, heart rate, arrhythmias and early clinical course. 167 47

516 patients with New York Heart Association class III and IV heart failure despite treatment with diuretics and angiotensin converting enzyme inhibitors were randomised in a double-blind between-group comparison to xamoterol 200 mg (352) or placebo (164) twice daily for 13 weeks. There was no difference between the treatments in loss of clinical signs. Visual analogue scale and Likert scores indicated that breathlessness was less severe with xamoterol, but there was no difference in exercise duration or total work done. Xamoterol reduced maximum exercise heart rate and systolic blood pressure, did not affect the number of ventricular premature beats after exercise, showed no arrhythmogenic activity, and had variable (agonist and antagonist) effects on 24 h heart rate. On intention-to-treat analysis 32 (9.1%) patients in the xamoterol group and 6 (3.7%) patients in the placebo group died within 100 days of randomisation (p = 0.02).
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PMID:Xamoterol in severe heart failure. The Xamoterol in Severe Heart Failure Study Group. 197 33

In order to assess potential harmful effects of the partial beta-1 agonist xamoterol during long-term therapy, we randomly assigned 30 patients with coronary arterial disease and heart failure in classes II and III of the classification of the New York Heart Association to 200 mg of xamoterol twice daily or placebo during a treatment period of 3 months. A supine bicycle exercise test was performed at baseline and after three months in order to assess changes of exercise capacity. Blood samples for determination of creatinine, electrolytes, renin and norepinephrine were withdrawn simultaneously. Twenty-four hour ambulatory Holter electrocardiograms were performed before study, at the end of the study and 72 hours after withdrawal of study medication. On xamoterol, exercise capacity increased from 21.9 +/- 9.7 to 27.8 +/- 14.8 kilojoule (P = 0.032) compared to baseline levels. Exercise duration increased from 340 +/- 115 to 400 +/- 144 seconds (P = 0.043). Heart rate decreased by 10% (P = 0.05) at the 50 watt level and by 10% (P = 0.024) on maximum exercise compared to the baseline values. The rate pressure product was unchanged at rest and dropped by 11% (P = 0.038) on maximum exercise. In contrast, on placebo no significant changes occurred. During xamoterol therapy no changes of blood pressure, electrolytes, renal function and the time-intervals of electrocardiogram were observed. Xamoterol did not enhance arrhythmias during 24-hour ambulatory Holter monitoring. No serious side effects were observed. Xamoterol would appear to be a suitable and safe drug in the therapy of mild to moderate heart failure.
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PMID:Exercise capacity, arrhythmias, humoral and chemical parameters during long-term therapy with xamoterol. 169 69

The sympathetic nervous system becomes activated in heart failure, and while this is initially beneficial, the consequences of prolonged raised levels of catecholamines can be counterproductive. Xamoterol, a partial agonist that acts on the cardiac beta 1-adrenergic receptor, modifies the response of the heart to variations in sympathetic activity. At rest, it produces modest improvements in cardiac contractility, relaxation, and filling without increase in myocardial oxygen demand. The improvements are maintained during exercise although the attendant tachycardia is attenuated. The beneficial effects of xamoterol on both systolic and diastolic function suggested that it would be effective in patients with mild-to-moderate heart failure, and this was demonstrated in small placebo-controlled studies where effort tolerance and symptoms were improved. A large multicenter study program comprised of four studies demonstrated that patients with mild-to-moderate heart failure randomized to xamoterol (n = 617) 200 mg b.i.d. for 3 months significantly (p less than 0.0001) improved exercise capacity by 37% as compared with the placebo group (n = 300) with an increase of 18%. The xamoterol group also showed significant improvements in symptoms of breathlessness, fatigue, and life values as compared with the placebo group. In one of the multicenter studies in which 433 patients were randomized to xamoterol (n = 220), placebo (n = 109), and a positive control, digoxin 0.125 mg b.i.d. (n = 104), the percentages of improvement in exercise work were 33%, 5%, and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Review of clinical experience with xamoterol. Effects on exercise capacity and symptoms in heart failure. 196 61

The effects of an intravenous injection of 0.15 mg/Kg of xamoterol were studied non-invasively under basal conditions and during beta-1-adrenergic stimulation with dobutamine in 16 patients with dilated cardiomyopathy and severe cardiac failure. Xamoterol did not cause any detectable agonist effect but was well tolerated under basal conditions. Its potential antagonist effect was only detected during the dobutamine infusion: xamoterol significantly reduced the increase in heart rate (p less than 0.001), the systolic blood pressure (p less than 0.01), the rate-pressure product (p less than 0.001) and the cardiac index (p less than 0.001) produced by the administration of dobutamine.
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PMID:[Noninvasive evaluation of partial beta adrenergic agonist properties of xamoterol in cardiac insufficiency]. 196 39

Xamoterol is a beta-1 selective partial adrenoceptor agonist. Thirty patients (one female, 29 male, mean age 56 +/- 8 years) with coronary artery disease and mild to moderate heart failure, according to NYHA classes II and III, were studied before and 15 min after intravenous administration of 0.2 mg/kg xamoterol, at rest and during standard, supine bicycle exercise. At rest, the pulmonary capillary wedge pressure fell by 39% (p = 0.0001) and the cardiac index increased by 7% (p = 0.0084); heart rate increased only slightly. With exercise, cardiac index did not change and the pulmonary capillary wedge pressure decreased by 11% (p = 0.0003). In addition, the heart rate dropped from 115 to 105 bt/min (p = 0.0001) which resulted in a decrease of the rate pressure product by 9% (p = 0.0041). Arterial blood pressure remained unchanged. Norepinephrine plasma levels did not change at rest or during exercise, whereas at rest plasma renin activity dropped by 18% (p less than 0.05) and by 20% (p less than 0.05) during exercise. No untoward side effects were observed and the drug was well tolerated. In conclusion, xamoterol, given acutely to patients with heart failure NYHA classes II or III exerted advantageous hemodynamic effects at rest and during exercise.
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PMID:[Hemodynamic and humoral changes following intravenous administration of xamoterol in patients with heart failure and coronary heart disease]. 196 85


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