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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 known properties of xamoterol, a partial beta 1-agonist, provide a basis to pharmacologically modulate cardiac responses to variations in sympathetic tone. Haemodynamic variables were assessed at rest and on exercise before and after intravenous xamoterol (0.2 mg kg-1), in 30 patients with mild to moderate cardiac failure. Xamoterol produced significant improvements in resting cardiac index (2.51 +/- 0.15 to 2.80 +/- 0.14 l min-1 m-2; P less than 0.001), stroke volume (62 +/- 4 to 75 +/- 5 mljbeat-1; P less than 0.001) and stroke work index (42.4 +/- 3.6 to 47.7 +/- 3.9 gm beat-1 m-2; P less than 0.01). This occurred despite a significant reduction in heart rate (78 +/- 3 to 74 +/- 2 beats min-1; P less than 0.05). There were also significant reductions in systemic vascular resistance (1990 +/- 141 to 1669 +/- 112 dynes s-1 cm-5; P less than 0.01) and double product (1146 +/- 46 to 1051 +/- 41 mmHg min-1 x 10(-1); P less than 0.05), with no significant changes in systolic blood pressure, pulmonary wedge pressure or ejection fraction. Xamoterol significantly attenuated the heart rate response to exercise (112 +/- 4 to 97 +/- 3 beats min-1; P less than 0.001), with no impairment in the expected exercise induced increase in cardiac index. This was due to the significant increase in stroke volume from 81 +/- 6 to 95 +/- 7 ml beat-1 (P less than 0.001). There were no significant changes in resting or exercise noradrenaline levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The acute effects of intravenous xamoterol ('Corwin', I.C.I. 118, 587) on resting and exercise haemodynamics in patients with mild to moderate heart failure. 256 33

Xamoterol, a partial agonist of beta 1-adrenoceptors, was tested as a cardiotonic drug in 10 patients with moderate chronic heart failure. The trial was double-blind drug versus placebo for 3 months and open for one year. At 3 months the patients were clinically improved with downgrading by one NYHA class, and there was a significant increase in response to a 36-second exercise, as compared with the placebo group. Haemodynamic index, a 14 per cent fall in pulmonary wedge pressure and a 7 per cent increase in left ventricular stroke work as compared with the placebo group. This clinical and haemodynamic improvement was paralleled by a reduction of the double product on exercise. In long term use, xamoterol did not seem to induce tachyphylaxis, and few side-effects were recorded during this trial.
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PMID:[Effects of xamoterol in moderate cardiac insufficiency]. 256 61

The possible cardiovascular pharmacodynamic interactions at rest and during exercise of combining oral flosequinan (100 mg) with xamoterol (200 mg) was investigated in a four-way randomised double-blind placebo-controlled crossover trial in eight healthy male volunteers. Xamoterol was better tolerated than flosequinan. The most common adverse events were mild to moderate headache and facial flushing. One volunteer developed headache and vomiting following flosequinan treatment and was replaced. Compared to placebo, at supine rest, flosequinan significantly increased heart rate (HR) by 5 beats.min-1, but had no effect on cardiac output (CO), stroke volume (SV) and mean blood pressure (MBP). Xamoterol significantly increased CO by 1.5 l.min-1, HR (5 beats.min-1) and MBP (6 mmHg) but not SV. The combined treatment (flosequinan + xamoterol) significantly increased CO (1.7 l.min-1) and HR (10 beats.min-1), but had no effect on SV and MBP. During exercise, flosequinan had no significant effect on any variable compared to placebo. Both xamoterol and combined treatment reduced the increase in CO (-4.6 l.min-1 after xamoterol and -3.4 l.min-1 after combined treatment vs. 0.1 l.min-1 after placebo), but had no effect on other variables. The effect of the combined treatment on each haemodynamic variable were no more than the anticipated additive effects of the two drugs. Thus, no cardiovascular pharmacodynamic interaction was found between flosequinan and xamoterol in healthy volunteers.
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PMID:Lack of pharmacodynamic interactions between acute dose flosequinan and xamoterol. A pilot study in healthy subjects. 795 23

The central haemodynamic effects of pindolol and xamoterol have been investigated in patients with postural hypotension. Pindolol is a non-selective beta-adrenoceptor partial agonist, whereas xamoterol is beta 1-selective and possesses a higher degree of agonist activity. The study comprised 16 patients with postural hypotension of different aetiologies. Blood pressure, heart rate and stroke volume were measured in the supine and head-up tilted positions. Left ventricular ejection fraction (LVEF) was measured in the supine position, and vascular resistance, left ventricular volume, and left ventricular contractility were derived. Pindolol and xamoterol were administered intravenously in incremental doses to reach total doses of 0.02 and 0.20 mg.kg-1, respectively. Pindolol showed beta-adrenoceptor antagonistic effects in the supine position through decrements in heart rate from 70 to 66 beats.min-1 and LVEF from 0.57 to 0.52, and reduced mean arterial blood pressure from 103 mm Hg to 93 mm Hg. Xamoterol showed beta-adrenoceptor agonistic effects in the supine position through increments in heart rate from 72 to 90 beats.min-1 and LVEF from 0.58 to 0.66, and raised mean arterial blood pressure from 108 to 123 mm Hg. It is concluded that the degree of agonist activity of a beta-adrenergic agent is of importance if it is given to a patient with postural hypotension.
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PMID:Differential effects of beta-adrenoceptor partial agonists in patients with postural hypotension. 843 59