摘要:

The aim of the study was to compare the effects of atenolol (50 mg b.i.d.), verapamil (80 mg b.i.d.), xamoterol (200 mg b.i.d.), and matching placebo on heart rate (HR) and exercise tolerance in digitalised patients with chronic atrial fibrillation. Each treatment was taken for 4 weeks, and digoxin was continued throughout the study. During treatment with placebo (digoxin alone), the mean postexercise heart rate was 164 beats/min, and four subjects had rates of 2≥170 beats/min. Atenolol, verapamil, and xamoterol achieved significantly better control of exercise-induced tachycardia, mean postexercise heart rates being reduced to 120, 131, and 130 beats/min, respectively (p < 0.01 for each). However, minimum HRs ≤ 45 beats/min occurred during treatment with placebo, atenolol, and verapamil, whereas treatment with xamoterol was associated with a minimum heart rate of 56 beats/min. Treatment with atenolol was associated with a marked reduction in maximum treadmill walking distance (mean 356 m) as compared both with placebo (mean 421 m, p < 0.01) and verapamil (mean 439 m, p < 0.01). Xamoterol reduced maximum walking distances as compared with verapamil (402 vs. 439 m; p < 0.05) but not placebo (402 vs. 421 m; NSS). Thus, atenolol, verapamil, and xamoterol achieved better control of exerciseinduced tachycardia than digoxin, but atenolol clearly impaired exercise tolerance whereas verapamil did not. Xamoterol achieved more even control of ventricular response rates and prevented the resting bradycardias that occurred with the other treatments. However, walking distances were significantly lower than those noted during treatment with verapamil.

ISSN:0160-2446    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Rat kidney glomeruli and cortical tubules were obtained by a combination of sieving and differential centrifugation technique. [3H]Prazosin and [3H]rauwolscine were used to identify and quantify the α- and α-adrenergic receptors, respectively. In the glomeruli, the α,-adrenoceptor concentration was 27% and α-adrenoceptor concentration was 33% of the corresponding values in the tubules. Further localization of the tubular α-adrenoceptors was undertaken by studies in the isolated basolateral membrane and comparison with values in the crude plasma membrane. α-Adrenoceptors were enriched 1.54 ± 0.1 times and α-adrenoceptors were enriched 1.73 ± 0.04 times in the basolateral membrane as compared to crude plasma membrane. However, these values were significantly (p < 0.05) less than the enrichment value of 2.77 ± 0.3 obtained for the basolateral membrane marker (Na++ K+)-ATPase. These results suggested the possibility that α- and α-adrenoceptors may also be distributed in the brush border membrane. Direct-binding studies in the purified renal brush border membrane indicated α-adrenoceptor concentration of 82.1 ± 3.8 and α-adrenoceptor concentration of 108.2 ± 9.3 fmol/mg protein. These values were 32 and 17% of the corresponding values in the basolateral membrane. Overall, our results suggest that α- and α-adrenoceptors are present both in the basolateral and brush border membranes analogous to what has been reported for angiotensin and insulin receptors; their primary concentration, however, is in the basolateral membranes.

ISSN:0160-2446    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

SK&F 86466 is a novel α-adrenoreceptor blocking drug shown in preclinical profiling to have relative selectivity for the pre- and postjunctional α-adrenoreceptor. In the present clinical study, the effects of single oral doses of 10, 25, and 50 mg SK&F 86466 on supine and stimulated circulatory and neuroendocrine function were assessed in eight normal subjects studied in a placebo-controlled balanced cross-over design with the drugs administered in double-blind fashion. SK&F 86466 caused a dose-related increase in stimulated (postural and cold challenge) and supine plasma norepinephrine (NE) concentrations. This increase was associated with an increase in supine heart rate (HR) and plasma renin activity and orthostatically stimulated HR, with little increase in systolic blood pressure (SBP) and no increase in diastolic blood pressure (DBP). Assuming that no changes occurred in catecholamine clearance, SK&F 86466 thus appeared to have a prejunctional α-adrenoreceptor blocking effect, which was countered by a postjunctional α-adrenoreceptor blocking effect at the level of the resistance vessels, whereas this latter effect did not alter the pressor responses to cold and postural challenge.

ISSN:0160-2446    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We compared the efficacy of flecainide versus quinidine in preventing paroxysms of atrial fibrillation in a randomized open crossover study. Twenty-six patients with weekly attacks of atrial fibrillation during the last 3 months, objectified by 24-h holter monitoring or 12-lead electrocardiogram (ECG) were treated for a period of 3 months with flecainide 100 mg b.i.d. or quinidine 500 mg b.i.d. Efficacy was assessed by 24-h holter monitoring and a questionnaire at the end of each month. Dosage was adjusted to flecainide 100 mg t.i.d. or quinidine 500 mg t.i.d. if patients still had symptomatic paroxysms of atrial fibrillation according to a questionnaire or on holter monitoring. In 46% of the patients, flecainide 100 mg b.i.d. caused total abolition of supraventricular tachycardia; after dose adjustment it caused 50% total abolition. For quinidine, the figures are 16% (p &lt; 0.05) and 32% (NS), respectively. Side effects occurred with flecainide only after dose adjustment (23%), but on quinidine they occurred before (8%) and after dose adjustment (20%). We conclude that flecainide suppresses paroxysms of atrial fibrillation significantly more often as compared with quinidine in the lower dosage regimen. Optimal treatment dosage of flecainide is 100 mg b.i.d. After quinidine dose adjustment, the difference in efficacy is no longer significant. However, side effects necessitating discontinuation of quinidine developed in 20% of the patients as compared to none in patients treated with flecainide 100 mg b.i.d.

ISSN:0160-2446    

出版商:OVID    

年代:1989

数据来源: OVID