Integrated effects of the vasodilating beta-blocker nebivolol on exercise performance, energy metabolism, cardiovascular and neurohormonal parameters in physically active patients with arterial hypertension.

OBJECTIVE: The present study was designed to investigate the integrated effects of the beta-1-selective blocker with vasodilator properties, nebivolol, on systemic haemodynamics, neurohormones and energy metabolism as well as oxygen uptake and exercise performance in physically active patients with moderate essential hypertension (EH). DESIGN AND METHODS: Eighteen physically active patients with moderate EH were included: age: 46.9 +/- 2.38 years, weight: 83.9 +/- 2.81 kg, blood pressure (BP): 155.8 +/- 3.90/102.5 +/- 1.86 mm Hg, heart rate: 73.6 +/- 2.98 min(-1). After a 14-day wash-out period a bicycle spiroergometry until exhaustion (WHO) was performed followed by a 45-min submaximal exercise test on the 2.5 mmol/l lactate-level 48 h later. Before, during and directly after exercise testing blood samples were taken. An identical protocol was repeated after a 6-week treatment period with 5 mg nebivolol/day. RESULTS: Nebivolol treatment resulted in a significant (P < 0.01) decrease in systolic and diastolic BP and heart rate at rest and during maximal and submaximal exercise. Maximal physical work performance, blood lactate and rel. oxygen uptake (rel. VO(2)) before and after nebivolol treatment at rest and during maximal and submaximal exercise remained unaltered. Free fatty acid, free glycerol, plasma catecholamines, beta-endorphines and atrial natriuretic peptide (ANP) increased before and after treatment during maximal and submaximal exercise but remained unaltered by nebivolol treatment. In contrast, plasma ANP levels at rest were significantly higher in the presence of nebivolol, endothelin-1 levels were unchanged. CONCLUSIONS: Nebivolol was effective in the control of BP at rest and during exercise in patients with EH. Furthermore, nebivolol did not negatively affect lipid and carbohydrate metabolism and substrate flow. The explanation for the effects on ANP at rest remain elusive. This pharmacodynamic profile of nebivolol is potentially suitable in physically active patients with EH.

[The role of routine chest radiography after percutaneous dilatational tracheostomy. A prospective randomized study]. / Bedeutung der routinemäßigen Röntgenkontrolle nach perkutaner Dilatationstracheotomie. Eine prospektive randomisierte Studie.

BACKGROUND: Routine chest radiography (X-ray) after percutaneous dilatational tracheostomy has been considered standard procedure in the past. However, recent observations show this to be unnecessary and cost ineffective. Prospective randomised trials have been lacking. PATIENT AND METHODS: Critically ill patients admitted to an ICU with an indication for a percutaneous tracheostomy were consecutively randomized into group 1 (routine postprocedural chest X-ray) and group 2 (chest X-ray only when considered clinically indicated). Tracheostomy was performed under bronchoscopic guidance. RESULTS: A total of 100 patients (50 per group) were included. Three major complications were observed in group 1 and one presumed complication in group 2. There were 11 minor complications in group 1 and 16 in group 2. Routine chest X-ray in group 1 did not reveal any abnormality related to the tracheostomy. A control chest X-ray was considered necessary in only one patient in group 2, but with no pathological change observed. CONCLUSION: Routine chest radiography after a percutaneous dilatational tracheostomy conducted under fibre optic bronchoscopic guidance is probably not useful.

[Nebivolol, a beta blocker of the 3rd generation: modern therapy of arterial hypertension. Results of a multicenter observation study]. / Nebivolol, ein Betablocker der 3. Generation: Die moderne Therapie der arteriellen Hypertonie. Ergebnisse einer multizentrischen Beobachtungsstudie.

BACKGROUND: Nebivolol represents a therapeutic class of beta blockers with high beta 1 selectivity and modulatory effect on vascular reactions by releasing nitric oxide (NO) from endothelial cells. Its antihypertensive effect by once a day application is established. The aim of the study was to investigate the acceptability and the antihypertensive efficacy of Nebivolol in hypertensives with and without concomitant diseases. METHODS AND RESULTS: An observational study was carried out in 6376 patients with arterial hypertension in 1529 centres in a period of time of six weeks. The initial dosage was 5 mg daily resp. 2.5 mg daily in patients over 65 years. The systolic blood pressure (BP) decreased during treatment from initial values of 173 +/- 18 mm Hg (mean +/- standard deviation) by 29 mm Hg to 144 +/- 14 mm Hg at the end of the observational period. The diastolic BP decreased from 101 +/- 9 mm Hg initially by 16 mm Hg to 85 +/- 8 mm Hg at the last examination of the patients. The normalization of the diastolic BP (< 90 mm Hg) was achieved in 62.2% of the patients. The mean heart rate (HR) was 84 +/- 12 beats/minute at the beginning of the study and decreased by 11 to 73 +/- 8 beats/minute. During the observational period cholesterol, triglycerides and blood glucose showed a significant decrease (p < 0.001). Triglycerides were diminished by 13%, cholesterol by 8%. In diabetic patients the most favourable effect was observed (decrease of triglycerides by 18% and cholesterol by 9%); glucose decreased in diabetics by 16%. CONCLUSIONS: In this multicentre observational study Nebivolol was proved as a safe and well-tolerated antihypertensive drug. The results of the analysis of metabolic parameters during Nebivolol treatment are of interest as a contribution to the preventive effect of this beta blocker on coronary heart disease.

[Nebivolol, a third generation beta blocker: the modern treatment of hypertension. Results of a multicentric observational study]. / Nebivolol, ein Betablocker der dritten Generation: Die moderne Therapie der arteriellen Hypertonie. Ergebnisse einer multizentrischen Beobachtungsstudie.

BACKGROUND: Nebivolol represents a new therapeutic class of beta blockers with high beta1 selectivity and the ability to modu late the direct vascular reactions through the liberation of nitric oxide (NO) by the endothelial cell. Its antihypertensive action develops at a once-daily dosage. The main aim of the study was to determine the tolerability and antihypertensive efficacy of nebivolol in hypertensives with or without concomitant diseases. METHODS AND RESULTS: The observational study was carried out in 1529 centers on 6376 patients with hypertension over a period of 6 weeks. The initial daily dosage was 5 mg or 2.5 mg in patients older than 65. Under treatment, the systolic blood pressure decreased by a mean (+/- 1 standard deviation) of 29 mmHg (+/- 17 mmHg) from 173 mmHg (+/- 18 mmHg) initially, to 144 mmHg (+/- 14 mmHg) by the end of the observation period. The diastolic blood pressure decreased by a mean of 16 mmHg (+/- 10 mmHg) from 101 mmHg (+/- 9 mmHg) initially to 85 mmHg (+/- 8 mmHg) by the end of the observation period (p < 0.001). Normalization of the diastolic blood pressure (< 90 mmHg) was achieved in 62.2% of the patients. The mean heart rate at the start of the study was 84 (+/- 12) vs. 73 (+/- 8) beats per minute by the end of the study (reduction: 10.6 +/- 10.3 beats per minute). The decrease in blood pressure and heart rate depended on the baseline values, that is, higher blood pressure and higher heart rates initially showed a greater reduction (both parameters) in comparison with moderately elevated initial values. Cholesterol, triglycerides and blood sugar decreased significantly (p < 0.001) duringthe observation period. For triglycerides the decrease was 13%, for cholesterol 8%. Diabetics benefited most (reduction in triglycerides 18%, in cholesterol 9%); here, the glucose concentration decreased by 16%. Physician-assessment of the efficacy of nebivolol was 93%, tolerability 97% (very good or good). CONCLUSION: In this large multicentric observational study, the substance nebivolol proved to be a safe, largely side effect-free antihypertensive. Its favorable metabolic properties must be considered positive, in particular with regard to the possible development of coronary heart disease.

[Nebivolol (nebilet) a beta blocker of the third generation--also for patients with obstructive lung diseases?]. / Nebivolol (Nebilet)--ein sicherer Betablocker der dritten Generation--auch für Patienten mit obstruktiven Lungenerkrankungen?

UNLABELLED: Twenty-four patients with bronchial hyperreactivity due to asthma (8 patients), COPD (13) and of unknown origin (3) entered and completed a randomized double-blind intraindividual cross-over study. Thirteen patients first received the highly selective vasodilatating beta 1-blocker Nebivolol (5 mg) and 11 patients first placebo with a wash-out period of at least 2 days. Before the controlled oral intake of the tablets, the patients were challenged with increasing inhalative doses of carbachol between 8 and 9 a.m. according to the recommendation of the German Society of Pneumology. At 10, 11 and 12 a.m. and 1 and 2 p.m. control measurements of airway patency (Raw, FEV1) were performed in the body box. At the same time intervals, oxygen saturation and pulse rate (pulsoximetry) including systolic and diastolic blood pressure were monitored. From 2-3 p.m. the carbachol provocation was repeated as in the morning to assess the changes in hyperreactivity due to Nebivolol. RESULTS: During the Nebivolol phase, blood pressure values and pulse rates were significantly reduced compared to the placebo phase. At the same time intervals, no significant changes of the measured body box variables to assess airway obstruction were observed during therapy with Nebivolol compared to placebo. Comparing the measured variables (maximal deviation from base-line values of Raw and FEV1) during carbachol provocation in the afternoon under Nebivolol and placebo with the values in the morning before any medication (base-line values), there were also no significant detectable differences indicating an increase of bronchial hyperreactivity under Nebivolol treatment. CONCLUSION: It seems that Nebivolol in these hyperreactive patients is as safe as placebo despite its significant effect on blood pressure and pulse rate.

Beta-blockers of the third generation inhibit endothelin-1 liberation, mRNA production and proliferation of human coronary smooth muscle and endothelial cells.

Endothelin-1 (ET-1) plays an important role in atherogenesis. The aim of the study reported here was to investigate the effects of the third generation beta-blockers nebivolol and carvedilol on ET-1 liberation, preproendothelin-1 production and on proliferation of human coronary cells. Human coronary endothelial (HEC) and smooth muscle cells (HCSMC) were grown with carvedilol or nebivolol (10(-7)-10(-5) mol/l). Incubation for 1, 2 or 7 days resulted in an 80% concentration- and time-dependent reduction in HCSMC proliferation. beta-blockers such as propranolol or metoprolol did not influence cell proliferation. Nebivolol (10(-7) mol/l) inhibited accelerated HCSMC proliferation in the presence of growth factors such as transforming growth factor-beta1 or platelet-derived growth factor BB. During incubation with nebivolol or carvedilol ET-1 secretion decreased. For nebivolol this is a result of a reduction in preproendothelin-1 mRNA levels. beta-blockers of the third generation that reduce the cell proliferation and ET-1 secretion may represent strategies with great promise for antiproliferative therapy of coronary heart disease.

[Danazol for treatment of fibrocystic mastopathy]. / Danazol für die Behandlung der fibrozystischen Mastopathie.

59 patients with extensive mastopathia, aged between 23 and 58 years, had been examined over a period of approximately 36 months. They were treated with danazol (Winobanin, Sanofi-Winthrop, Munich) at doses between 100 and 800 mg/day because of an extensive and partly persisting mastopathia. The documented period of treatment ranged between 40 and 774 days. According to the chosen medium daily dose the patients were divided into three groups (< 400 mg/d, 400-600 mg/d, > 600 mg/d). These groups were then subdivided according to criteria of symptoms, palpation findings, mammography and sonography. Between the onset and the end of treatment there was a significant improvement of mastopathia up to a complete recovery in more than 60% of the women. There were no significant systematic differences between the various dosages of danazol. In this respect it was impossible to verify assumed relation between dosage and success of treatment according to anamnestic or demographic factors. The objective evaluation by mammography and ultrasound showed an improvement in 81.4% of the patients, demonstrated by a decreased density of parenchyma and an increased subcutaneous fatty tissue of the mammae. The subjective success of therapy of the patients concerned was judged to be good in 75% of the cases by the doctor and in more than 63% by the patient herself. In conclusion, this study confirms that danazol offers very good therapeutic results for the treatment of the frequently persisting benign breast disease.