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

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

More and more patients with coronary heart disease (CAD) are admitted to intensive care units. The drugs used to treat these patients have various effects on the myocardium which must be known in order to avoid worsening the CAD. This review examines the metabolic effects on the myocardium of the most commonly used drugs in intensive care. The physiology of myocardial oxygen supply is first recalled with regard to the coronary circulation, myocardial oxygen extraction and consumption. Digitalis glycosides do not affect the coronary circulation, but the decrease myocardial oxygen consumption in patients with heart failure, mainly by lowering heart rate. Dihydropyridine calcium blockers (nifedipine, nicardipine) increase coronary blood flow, despite a decrease in arterial blood pressure. Their effects on myocardial oxygen consumption are mediated by a sympathetic reflex. Verapamil decreases the heart rate and myocardial inotropism, and is responsible for coronary vasodilation. The result is a decrease in myocardial oxygen consumption. Diltiazem and bepridil have almost similar effects: they decrease myocardial oxygen consumption and increase blood supply to the heart. It has been recently shown that verapamil was the most depressant calcium channel blocking agent, and that it resulted in the most important decrease in myocardial metabolism. Beta-blocking agents decrease myocardial metabolism, except those with an important intrinsic sympathomimetic activity, such as pindolol. Amiodarone can be considered as an alpha and beta blocking drug: its main effect is to counteract the effects of endogenous catecholamines on myocardial metabolism. The sympathomimetic amines (noradrenaline, adrenaline, isoprenaline, dopamine, dobutamine) increase, to different extents, myocardial oxygen consumption. Vasodilators, such as the nitrates or sodium nitroprusside, decrease cardiac filling pressures, and increase myocardial blood flow, thus lowering myocardial oxygen consumption. Phosphodiesterase inhibitors (amrinone, enoximone) have both an inotropic and a vasodilating effect. They decrease cardiac afterload, and increase blood supply to the myocardium; this compensates for the increase in myocardial oxygen consumption due to the increase in myocardial contractility. Because all the drugs used in intensive care have different effects on myocardial metabolism, their reasoned use should avoid an inappropriate increase in oxygen demand.
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PMID:[Changes in myocardial metabolism induced by drugs used during intensive care]. 197 Apr 63

As the dual pharmacological action of partial beta 1-adrenoceptor agonists should improve left ventricular function while also protecting the myocardium against excessive sympathetic stimulation they may be useful in the treatment of heart failure. Therefore, we studied the pharmacological effects of xamoterol (Corwin, ICI 118, 587), a compound with mixed agonist and antagonistic properties at cardiac beta-adrenoceptors in electrically driven human papillary muscle strips from failing human hearts. Specimens were obtained from patients with different grades of myocardial failure who underwent mitral valve replacement (NYHA II-III) or heart transplantation (NYHA IV). Xamoterol (0.0001-100 mumol l-1) produced only negative inotropic effects, as measured by changes in isometric force of contraction in diseased human papillary muscle strips. However, isoprenaline (0.0001-10 mumol l-1) and ouabain (0.01-0.3 mumol l-1) enhanced force of contraction in the same hearts. Prestimulation with noradrenaline (3 mumol l-1) augmented the negative inotropic effect of xamoterol. It is concluded that xamoterol exerts primarily beta-adrenoceptor antagonistic activity in the failing human myocardium.
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PMID:The effect of xamoterol in failing human myocardium. 197 May 36

Xamoterol is a beta 1-selective adrenoceptor partial agonist. The acute effects of xamoterol were studied in 30 patients with ischaemic heart failure. Haemodynamic data were assessed at baseline, at rest and after supine bicycle exercise (50 W for 3 min), and repeated 15 min after xamoterol (0.2 mg kg-1) given by infusion over 5 min. At rest, xamoterol increased heart rate, mean blood pressure and cardiac index, and reduced pulmonary wedge pressure. On exercise, heart rate fell while cardiac index was maintained and pulmonary wedge pressure fell slightly but significantly. There was a tendency for plasma renin activity and plasma noradrenaline to fall both at rest and on exercise. The clinical relevance of these haemodynamic and neurohumoral changes were examined in conjunction with the German-Austrian Xamoterol Group's study, screening 443 patients with mild to moderate heart failure and giving xamoterol or placebo for 3 months as part of a randomized, double-blind study. The German experience was then placed in context of the pooled world-wide database of efficacy and safety in three other large (greater than 100 patients) studies with xamoterol in mild to moderate heart failure. In brief, this overview demonstrated a 2.98 +/- 0.68 kJ improvement in work done over placebo, equivalent to 14% (xamoterol) and 6% (placebo) improvements over baseline (P less than 0.0001). Xamoterol is thus a promising new approach to the treatment of mild to moderate heart failure.
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PMID:Sympathetic modulation in practice: the German clinical experience. 197 86

Xamoterol is a selective partial beta-adrenoceptor agonist. In a double-blind randomized placebo-controlled study, 30 patients (1 female, 29 male) with mild to moderate heart failure were treated with 200 mg of xamoterol twice daily or placebo during 3 months. At baseline and 72 h after the last tablet intake, the hemodynamic and humoral effects of a single intravenous dose of xamoterol (0.2 mg/kg) were assessed by right heart catheterization. At baseline, intravenous xamoterol raised resting heart rate by 3% (NS) in the placebo and by 6% (NS) in the xamoterol group. On exercise, heart rate was reduced by 10% (p = 0.015) and 7% (p = 0.016), respectively. Pulmonary capillary wedge pressure (PCWP) dropped in both groups: at rest by 4 mm Hg (p = 0.0004) in the placebo group and by 6 mm Hg (p = 0.0002) in the xamoterol group; on exercise by 1 mm Hg (NS) in the placebo and by 6 mm Hg (p = 0.0001) in the xamoterol group. Similar changes of all variables were obtained after long-term therapy in both groups. Mean arterial blood pressure, cardiac index and systemic vascular resistance did not change importantly. Norepinephrine levels did not change, but plasma renin activity decreased at baseline as well as after long-term therapy in both groups by similar amounts. Thus, no signs of tolerance development were observed after an oral treatment with 200 mg of xamoterol twice daily during 3 months. However, xamoterol as a partial agonist exerted only weak changes of cardiac index and PCWP compared to full beta-adrenoceptor agonists. The drug was well tolerated, and serious side effects were absent.
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PMID:Lack of tolerance development after long-term administration of the partial beta-adrenoceptor agonist xamoterol. 197 49

This study reports the effects of the new beta 1 adrenoceptor partial agonist, xamoterol, on neuroendocrine activity after acute myocardial infarction (AMI). Fifty-one consecutive patients with AMI were randomized to treatment with xamoterol, 200 mg twice a day, or placebo; patients were also stratified as to whether or not diuretic therapy was given for left ventricular dysfunction. Noradrenaline, plasma renin activity (PRA), and atrial natriuretic factor (ANF) were measured over a 10-day period. Noradrenaline concentrations are higher (p less than 0.05) in patients treated with diuretics at the time of admission and fell over the subsequent 10 days (p less than 0.01). Treatment with xamoterol did not affect this noradrenaline response to myocardial infarction. PRA was also significantly higher in the patients treated with diuretics, and there was a nonsignificant trend for xamoterol to blunt the PRA response in these patients. There was no difference in ANF levels between those patients who were treated with diuretics and those who were not; xamoterol did not affect ANF. Thus xamoterol does not further elevate noradrenaline levels as do conventional beta blockers, and it does not activate the renin-angiotensin system as do potent nonselective beta agonists. Furthermore, xamoterol does not increase ANF levels, probably because it is not negatively inotropic. We conclude that xamoterol does not cause deleterious neuroendocrine changes in patients with AMI even in those treated for heart failure.
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PMID:Neuroendocrine changes post myocardial infarction: effects of xamoterol. 197 61

To study the haemodynamic and neurohumoral effects of nisoldipine (2 X 10 mg) vs captopril (3 X 25 mg), 24 patients with heart failure (New York Heart Association class II and III) due to coronary artery disease were treated in a randomized double-blind trial over 3 months. Both drugs were well tolerated. Clinical status was similarly improved in both groups, nisoldipine exerted an additional antiischaemic effect. Nisoldipine lowered the mean arterial pressure and capillary wedge pressure acutely and also after long-term treatment. The increase in cardiac index and stroke volume index, however, which was pronounced after acute administration, was no longer present after 3 months of therapy at rest and was abolished during exercise. Norepinephrine plasma concentration increased after the first dose, plasma renin activity did not change, and aldosterone plasma concentration showed a small insignificant decrease. Urine concentrations of norepinephrine and vasopressin were slightly elevated after the 3-month therapy. After captopril, mean arterial pressure and pulmonary capillary wedge pressure decreased acutely and at follow up. Cardiac index and stroke volume index increased significantly only during exercise at follow-up. Plasma renin activity was significantly elevated and aldosterone plasma concentration only slightly lowered. In contrast to what was seen with nisoldipine, plasma norepinephrine concentration and urine catecholamine and vasopressin concentrations remained unchanged. In conclusion, the pronounced haemodynamic effects seen after the first dose of nisoldipine are mostly abolished after long-term treatment, probably due to neurohumoral counterregulation. The haemodynamic response to captopril is complete only after long-term treatment, without evidence of activation of the neurohumoral systems.
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PMID:Acute and long-term haemodynamic and neurohumoral response to nisoldipine vs captopril in patients with heart failure: a randomized double-blind study. 168 8

On the basis of pathophysiologic mechanisms, the medical therapy of today for chronic heart failure is reviewed. The advantages and disadvantages of the vasodilator drugs and the inotropic drugs are presented. Finally, the therapeutic value of the inodilator drugs, which combine the central myocardial effects of positive inotropic agents with those of peripheral vasodilators, is discussed. In particular, the orally available dopaminergic agents, such as ibopamine, which interact with beta-receptors in the heart (mediating a positive inotropic effect) as well as with dopaminergic receptors in the peripheral vessels (mediating a systemic vasodilator effect) and in the kidneys (potentiating the natriuretic effect of diuresis), seem to be an advancement in the modern medical therapy of chronic heart failure. Data are shown during long-term treatment with ibopamine, in which the sustained clinical benefit in heart failure was not diminished, despite a decrease of the adrenergic receptors in blood cells. Dopamine plasma concentration was permanently normalized during long-term treatment. The discrepancy between clinical improvement and the measured adrenergic downregulation may be due to the interference of the inodilator with neurohormonal systems at multiple sites and is probably independent of receptor activation. It is suggested that the biosynthesis of noradrenaline is improved by increasing intracellular dopamine transport.
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PMID:Medical management of chronic heart failure: inotropic, vasodilator, or inodilator drugs? 197 81

In heart failure, an increase in the activity of the sympathetic nervous system takes place to maintain perfusion pressure to vital organs, resulting in increased levels of noradrenaline in the blood of these patients. This permanent stimulation produces a down-regulation of cardiac beta-adrenoceptors. Since noradrenaline acts primarily on the cardiac beta 1-adrenoceptor subtype, beta 1-adrenoceptors decrease in number, whereas the beta 2-adrenoceptor subpopulation remains unchanged in most instances. Consequently, the positive inotropic response to beta-adrenoceptor agonists is diminished. However, there is also a decrease in the positive inotropic effect of beta 2-adrenoceptor agonists, histamine and cAMP-phosphodiesterase inhibitors such as milrinone, whereas the positive inotropic effect of cAMP-independent Na(+)-channel activators such as DPI 206-106 and the effects of cardiac glycosides are not diminished. These observations suggest a more generalised alteration of the cAMP-adenylate cyclase system in the failing heart. Stimulatory guanine nucleotide-binding protein (Gs) couples receptors to adenylate cyclase that stimulate cAMP formation, such as beta-adrenoceptors, histamine receptors and glucagon receptors. In the failing human heart, Gs content has been reported to remain unchanged as compared with that in non-failing myocardium. However, there is a 35%-40% increase in inhibitory guanine nucleotide-binding proteins (Gi), which are involved in the receptor-mediated inhibition of adenylate cyclase. Taken together, two defects of the cAMP-adenylate cyclase system have been identified: an increase in Gi content and a decrease in the number of beta-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Alterations of the cAMP-adenylate cyclase system in the failing human heart. Consequences for the therapy with inotropic drugs]. 197 43

Hyperactivity of the noradrenergic sympathetic system is one of the essential "compensatory"mechanisms in chronic left ventricular failure. The ensuing stimulation of myocardial beta-adrenergic receptors results in an increase of heart rate and contractility which, to some extent, counterbalances the alteration of left ventricular function, but rapidly reaches its limits: the excessive shortening of diastoles and, mostly, the increase of myocardial oxygen demand neutralize the beneficial haemodynamic effect of beta-adrenergic stimulation, especially when ischaemia is the cause of the heart failure; the chronic exposure of adrenergic receptors to noradrenaline in high concentrations leads to desensitization, to a "down regulation" which primarily affects the beta 1 receptors and spares, at least partly, the myocardial beta 2 receptors which seem to play a quantitatively important inotropic role, particularly in chronic heart failure. These new data on the physiology of the cardiac noradrenergic system have major therapeutic consequences: in practice, the positively inotropic beta-stimulants can only be used for a short period in acute episodes of heart failure; - the use of beta-blockers in low doses is now considered in the treatment of some forms of heart failure; the mechanism of their therapeutic action remains controverted, and their long-term effectiveness in a large patient population is under study; - a new pharmacological class, beta-adrenoceptor partial agonists, seems to give satisfactory clinical and haemodynamic results in mode-rate heart failure, A wider clinical evaluation is needed to determine the therapeutic role of theses new pharmacodynamic agents.
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PMID:[The function of beta receptors in chronic left ventricular insufficiency]. 198 29


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