Time course for blood pressure lowering of beta-blockers with partial agonist activity.

BACKGROUND: Beta-blockers are commonly used in the treatment of hypertension. We do not know whether the blood pressure (BP) lowering efficacy of beta-blockers varies across the day. This review focuses on the subclass of beta-blockers with partial agonist activity (BBPAA). OBJECTIVES: To assess the degree of variation in hourly BP lowering efficacy of BBPAA over a 24-hour period in adults with essential hypertension. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for relevant studies up to June 2020: the Cochrane Hypertension Specialised Register; CENTRAL; 2020, Issue 5; MEDLINE Ovid; Embase Ovid; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We sought to include all randomised and non-randomised trials that assessed the hourly effect of BBPAA by ambulatory monitoring, with a minimum follow-up of three weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the included trials and extracted the data. We assessed the certainty of the evidence using the GRADE approach. Outcomes included in the review were end-point hourly systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), measured using a 24-hour ambulatory BP monitoring (ABPM) device. MAIN RESULTS: Fourteen non-randomised baseline controlled trials of BBPAA met our inclusion criteria, but only seven studies, involving 121 participants, reported hourly ambulatory BP data that could be included in the meta-analysis. Beta-blockers studied included acebutalol, pindolol and bopindolol. We judged most studies at high or unclear risk of bias for selection bias, attrition bias, and reporting bias. We judged the overall certainty of the evidence to be very low for all outcomes. We analysed and presented data by each hour post-dose. Very low-certainty evidence showed that hourly mean reduction in BP and HR visually showed an attenuation over time. Over the 24-hour period, the magnitude of SBP lowering at each hour ranged from -3.68 mmHg to -17.74 mmHg (7 studies, 121 participants), DBP lowering at each hour ranged from -2.27 mmHg to -9.34 mmHg (7 studies, 121 participants), and HR lowering at each hour ranged from -0.29 beats/min to -10.29 beats/min (4 studies, 71 participants). When comparing between three 8-hourly time intervals that correspond to day, evening, and night time hours, BBPAA was less effective at lowering BP and HR at night, than during the day and evening. However, because we judged that these outcomes were supported by very low-certainty evidence, further research is likely to have an important impact on the estimate of effect and may change the conclusion. AUTHORS' CONCLUSIONS: There is insufficient evidence to draw general conclusions about the degree of variation in hourly BP-lowering efficacy of BBPAA over a 24-hour period, in adults with essential hypertension. Very low-certainty evidence showed that BBPAA acebutalol, pindolol, and bopindolol lowered BP more during the day and evening than at night. However, the number of studies and participants included in this review was very small, further limiting the certainty of the evidence. We need further and larger trials, with accurate recording of time of drug intake, and with reporting of standard deviation of BP and HR at each hour.

Comparative efficacy and usefulness of acebutolol and diltiazem for the prevention of atrial fibrillation during perioperative time in patients undergoing pulmonary resection.

BACKGROUND: Postthoracic surgery atrial fibrillation (AF) is the most frequently occurring arrhythmia. Strategies for preventing AF have been amply evaluated, but currently there are no clearly defined guidelines for treatment of AF after thoracic surgery. METHODS: The study was prospective and randomized controlled trial. Acebutolol and diltiazem versus placebo were compared, among 117 patients postpneumonectomy or lobectomy at the Thoracosurgery Clinic, Poznan University of Medical Sciences in Poland. Patients who were enrolled in the study were randomly assigned to one of the three groups: those who received acebutolol (Group 1) or diltiazem (Group 2) and compared with patients without antiarrhythmic drugs (Group 0). Each group consisted of 39 patients. The patients were continuously monitored postoperatively with 24 ECG (Holter monitor) in the intensive care unit. RESULTS: In patients receiving acebutolol AF occurred in 5% compared with 23% of patients receiving diltiazem and 20% of patients receiving placebo (difference not statistically significant). CONCLUSIONS: Acebutolol and diltiazem appear to have been non-effective for the treatment or prevention of AF. Side effects were mild. In comparison to diltiazem, however, acebutolol had a beneficial effect on the circulatory system. Patients who had received acebutolol proved to have had fewer tachycardia episodes and supraventricular ectopy during the postoperative period. It seems that acebutolol can be useful, especially in patients with sympathetic activity dominance.

A population-based analysis of the class effect of beta-blockers after myocardial infarction.

BACKGROUND: Long-term treatment with beta-blockers reduces mortality after acute myocardial infarction (AMI). Whether beta-blockers exert a class effect is unknown. METHODS: We analyzed mortality after AMI in Canadian patients 65 years or older who were discharged from hospital with a diagnosis of AMI from April 1996 to March 2000. Administrative data from Quebec, Ontario, and British Columbia were merged. We compared patients prescribed with metoprolol, acebutolol, or atenolol within 90 days after discharge. RESULTS: Among 31576 patients, 67% were prescribed with metoprolol, 24% with atenolol, and 9% with acebutolol. Clinical characteristics and proportion of days covered with a beta-blocker prescription were similar across groups. Although controlling for time-dependent covariates representing current use and dosage, as well as for age, sex, congestive heart failure, and several other comorbidities, patients who filled a prescription for acebutolol (hazard ratio 0.71, 95% CI 0.62-0.81) or atenolol (hazard ratio 0.79, 95% CI 0.73-0.87) had significantly lower mortality in comparison with metoprolol. CONCLUSIONS: The higher mortality observed in patients receiving metoprolol compared with those receiving atenolol or acebutolol challenges the concept of a class effect of beta-blockers for secondary prevention of AMI.

[Interrelationship between changes of rate and variability of cardiac rhythm under influence of beta-adrenoblockers].

BACKGROUND: Beta-blocking agents (BB) decrease mortality particularly sudden in post-myocardial infarction patients and in patients with chronic heart failure that is closely related to heart rate (HR) lowering at rest. The hypothesis exists that BB decrease mortality due to increase of cardiac vagal activity. AIM: To evaluate the relation between HR changes on therapy with BB and changes in heart rate variability (HRV). MATERIAL AND METHODS: Sixty patients with arterial hypertension randomized in three groups were studied before and after treatment with atenolol (AT), acebutolol (AC) or talinolol (TL) until doses of 100, 600 and 300 mg/d correspondingly were reached or resting HR was decreased by 10 bpm. 24-hour Holter monitoring was used to measure HR and HRV indexes. RESULTS: Arterial blood pressure decreased significantly in every group. HR max, min and average decreased significantly on AT. AC and TL lowered HR max and AT average but did not change HR min. AT did not change SDNN, SDANN, TotP and ULFP, but AC and NL decreased them significantly (p < 0.001). AT increased SDNNind, VLFP (p < 0.002), rMSSD, pNNSO and HFP (p < 0.003), but did not change LFP. AC and TL did not change these indexes. Changes of HRV indexes were closely related to changes of HR particularly HR min (r=0.53 - 0.84). Linear regressions of these relations did not differ between three drugs except for low frequency indexes of HRV between AC and TL. According to the equations the differences in HRV indexes between the drugs were well explained by the differences in HR changes. When all patients were evaluated together statistical significance of increase in rMSSD, pNN50 and HFP was not reached until HR average decreased by 10 bpm or more. The effect of TL on HR and HRV is very similar to AC what suggests its intrinsic sympathomimetic activity or anticholinergic properties.

Arrhythmogenic right ventricular dysplasia in pregnancy: a case report.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by progressive fibrous or fibrofatty tissue replacement of the right ventricular myocardium. Interspersed adipocytes and fibrous tissue may provide foci for arrhythmias. The clinical spectrum of ARVD may include asymptomatic premature ventricular complexes to ventricular tachycardia and sudden death. There is currently little information about ARVD in pregnancy. CASE: A 29-year-old primigravida, diagnosed with ARVD 1 year prior to pregnancy, underwent a full-term, uncomplicated pregnancy and delivery while maintained on acebutolol and an implanted cardioverter defibrillator. Her infant was born without an apparent cardiac anomaly or heart rate abnormality. CONCLUSION: Successful management of pregnancy complicated by ARVD can be accomplished with an implanted cardioverter defibrillator and an antiarrhythmic agent. Such patients should be managed with close monitoring during pregnancy for signs and symptoms of arrhythmia and preventive obstetric care appropriate to their clinical profile to optimize normal deliveries.

First Case Report of Smith-Magenis Syndrome (SMS) Among the Arab Community in Nazareth: View and Overview.

Smith-Magenis syndrome (SMS0) is a complex and rare genetic multisystem disorder characterized by a variable pattern of cognitive deficits accompanied by a1 distinctive behavioral phenotype. SMS is characterized by subtle facial dysmorphology, short stature, sleep disturbances, and neurobehavioral abnormalities. Little is known about the manifestation of his unique case among Arab population and its strategic treatment.This study comes to present a case of SMS in an Arab newborn male who was born in spontaneous delivery on June 29, 2015, with tachypnea, tracheomalacia, and mild hypotonia. The newborn was admitted on the Neonatal Intensive Care Unit (NICU), and various laboratory examinations and clinical examinations were performed.Throughout his hospitalization, feeding difficulties appeared and thus a peripheral venous catheter was inserted in the left leg.After 22 days of follow-up and hospitalizations, the patient status improved and he was discharged with recommendations to be in follow up in pediatric outpatient clinic.However, notwithstanding the different investigations, intermittent tachypnea continued at a rate of 72 to 77 breaths/min. Search for diagnosis begin intensively owing to persistence of tachypnia, mild hypotonia, feeding difficulties, sleep disturbances, and mild dysmorphic facial features. Suspicions of genetic abnormalities were considered and blood samples were sent for chromosome analysis and for fluorescent in situ hybridization (FISH) testing.The genetic results revealed the following: cytogenetic findings: 46, XY, del(17)(p11.2) and the FISH results: del(17)(p11.2p11.2) (D17S29). The chromosome diagnosis revealed an interstitial deletion of 17p11.2 and the diagnosis of the SMS was confirmed.Accurate clinical diagnosis, therapeutic assessments and a holistic management plans, including multidiscipline therapeutic strategies, periodic neuro-developmental assessments, and an early intervention programs, are recommended.However, cytogenetic analysis or FISH using an RAI1-specific probe is the most frequently used technique for DS. Sleep and behavioral disturbances treatment include a combination of the daytime dose of acebutolol with an evening oral dose of melatonin. Melatonin as chronobiotic, antioxidant, and analgesic agent showed to be effective in different primary sleep disorders and in those associated with neurobehavioral disorders. Based on the beneficial effect of melatonin, it will be useful to use serum levels of melatonin as a follow-up test.

beta(1)-adrenergic antagonists improve sleep and behavioural disturbances in a circadian disorder, Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a clinically recognisable contiguous gene syndrome ascribed to interstitial deletions of chromosome 17p11.2. Patients have a phase shift of their circadian rhythm of melatonin with a paradoxical diurnal secretion of the hormone. Serum melatonin levels and day-night behaviour were studied in nine SMS children (aged 4 to 17 years) given acebutolol, a selective beta(1)-adrenergic antagonist (10 mg/kg early in the morning). Cardiac examination, serum melatonin, motor activity recordings, and sleep diaries were monitored before and after drug administration. The present study shows that a single morning dose of acebutolol suppressed the inappropriate secretion of melatonin in SMS. A significant improvement of inappropriate behaviour with increased concentration, delayed sleep onset, increased hours of sleep, and delayed waking were also noted. These results suggest that beta(1)-adrenergic antagonists help to manage hyperactivity, enhance cognitive performance, and reduce sleep disorders in SMS.

Efficacy and tolerance of antihypertensive treatment in men and women with stage 1 diastolic hypertension. Results of the Treatment of Mild Hypertension Study.

OBJECTIVE: To explore the sex-specific benefits and risks of treatment of stage 1 diastolic hypertension. METHODS: Participants were African-American and white hypertensive men (n = 557) and women (n = 345) (age range, 45 to 69 years) with a diastolic blood pressure less than 100 mm Hg. Participants were randomized to treatment with placebo, chlorthalidone (15 mg/d), acebutolol hydrochloride (400 mg/d), doxazosin mesylate (2 mg/d), amlodipine besylate (5 mg/d), or enalapril maleate (5 mg/d); all were given nutritional-hygienic intervention. RESULTS: After 4 years, women who were randomized to lifestyle intervention only were less likely to be receiving step 1 therapy alone (placebo) than men who were randomized to placebo therapy (46% vs 66%, respectively, P < .01). There were significantly greater decreases in the mean systolic blood pressure in both men and women who were assigned to treatment with active drugs compared with those participants who were receiving placebo therapy; differences among treatments with active drugs were similar between men and women. Men experienced larger falls in their total and low-density lipoprotein cholesterol and triglyceride levels regardless of the treatment assignment than did women; however, there were no significant sex-by-treatment interactions. Quality-of-life indexes were generally improved with active drug treatment compared with placebo therapy in both sexes; there was a sex-by-treatment interaction for the general health index. The relative risk (RR) for combined clinical events was similar in women (RR, 0.64; 95% confidence interval [CI], (0.36 to 1.16) and in men (RR, 0.67; 95% CI, 0.40 to 1.14) who were assigned to treatment with all active drugs combined, compared with those who were receiving placebo therapy. CONCLUSION: In these exploratory analyses, men and women who were assigned to treatment with active drugs experienced greater and generally similar benefits from treatment than those participants who were assigned to lifestyle intervention only.

Prevention of postischaemic ventricular fibrillation by long term beta adrenoceptor blockade with acebutolol in the anaesthetised dog.

Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment underwent the same procedure. Coronary ligations in the randomised study were performed during seven consecutive days, and four dogs were operated on each day. This schedule was chosen in order to measure acebutolol plasma concentrations just before ligation from 60 to 540 min after the last dose of the drug. Long term oral treatment with acebutolol protected against postischaemic ventricular fibrillation and significantly reduced the incidence of both early phase (0-10 min postocclusion) ventricular arrhythmias and ventricular fibrillation. As a result the outcome was significantly improved after 60 min of ischaemia in acebutolol compared with placebo treated animals. The results in the control animals were similar to those in the placebo treated dogs. The protective effect of long term oral treatment with acebutolol lasted for nine hours and was apparently independent of the plasma concentrations of the drug. These data show that improved outcome in this canine model is due to the prevention of ischaemia induced ventricular fibrillation by long term beta adrenoceptor blockade, which is able to overcome the effect, if any, of partial agonist activity of acebutolol. A direct myocardial anti-ischaemic effect might explain the effectiveness of long term oral treatment, which is independent of plasma concentrations of the drug.

Effect of beta-adrenergic receptor blockade on atrial natriuretic peptide in essential hypertension.

Plasma levels of atrial natriuretic peptide (ANP) were measured in 32 untreated subjects with essential hypertension and in 31 patients undergoing long-term treatment with beta-blockers. Patients receiving beta-blockers had significantly higher mean plasma ANP levels (72.0 +/- 36.0 [SD] pg/ml) than did untreated hypertensive subjects (39.8 +/- 15.8 pg/ml; p less than 0.01) and healthy normotensive controls (33.9 +/- 16.6 pg/ml; n = 61, p less than 0.01), while the mean plasma ANP concentration in untreated hypertensive subjects was not statistically different from that in control subjects. Administration of atenolol, 50 mg/day, for 4 weeks to 10 untreated subjects resulted in a significant (p less than 0.001) rise in plasma ANP levels (from 38.8 +/- 9.5 to 68.7 +/- 20.6 pg/ml). In 31 patients undergoing long-term treatment with beta-blockers, multivariate regression analysis revealed that age, pretreatment mean blood pressure, and plasma concentration of cyclic 3',5'-guanosine monophosphate (cGMP) were significant predictors of plasma ANP levels. These results suggest that beta-adrenergic receptor blockade in patients with essential hypertension elevates plasma ANP levels with a concomitant rise in cGMP concentrations, and that increased ANP in plasma may play a role in the compensatory mechanism that operates in response to beta-adrenergic receptor blockade.

Beta-adrenergic blocking treatment and 24-hour baroreflex sensitivity in essential hypertensive patients.

We dynamically evaluated the effects of beta-blockade on the sensitivity of arterial baroreflex control of heart rate in 10 mild or moderate essential hypertensive patients in whom blood pressure was recorded intra-arterially for 24 hours in ambulatory conditions. Twenty-four-hour baroreflex sensitivity was assessed by both (1) a time-domain approach based on the calculation of the slope of the regression line between linearly related progressive increases in systolic blood pressure and pulse interval (+PI/+SBP sequences) and decreases in systolic blood pressure and pulse interval (-PI/-SBP sequences) and (2) a frequency-domain approach, ie, the ratio between the spectral powers of pulse interval and systolic blood pressure around 0.1 Hz (alpha coefficient). Data were obtained before and after 1 month of administration of either acebutolol (n = 5) or labetalol (n = 5). Before treatment, the 24-hour average slopes of the +PI/+SBP and -PI/-SBP sequences were 4.36 +/- 0.32 and 4.05 +/- 0.27 ms/mm Hg, respectively, while the alpha coefficient was 7.78 +/- 0.7 ms/mm Hg. After beta-blockade, these values were increased by 25.3 +/- 6.8%, 25.0 +/- 8.0%, and 32.1 +/- 9.3%, respectively (P < .01 for all values). Thus, beta-blockers potentiate baroreflex sensitivity in daily life. Time-domain and frequency-domain methods yielded superimposable results in dynamically evaluating 24-hour baroreflex sensitivity and its changes after beta-blockade.

Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS)

Problems with sexual function have been a long-standing concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. The Treatment of Mild Hypertension Study (TOMHS) provides an excellent opportunity for examination of sexual function and effects of treatment on sexual function in men and women with stage I diastolic hypertension because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of 902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate). All participants received intensive lifestyle counseling regarding weight loss, dietary sodium reduction, alcohol reduction (for current drinkers), and increased physical activity. Sexual function was ascertained by physician interviews at baseline and annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported a problems with sexual function. In men, 12.2% had problems obtaining and/or maintaining an erection; 2.0% of women reported a problem having an orgasm. Erection problems in men at baseline were positively related to age, systolic pressure, and previous antihypertensive drug use. The incidences of erection dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months, respectively, and were related to type of antihypertensive therapy. Participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months than participants randomized to placebo (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more similar among treatment groups than at 24 months, with nonsignificant differences between the chlorthalidone and placebo groups. Incidence was lowest in the doxazosin group but was not significantly different from the placebo group. Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in the placebo group. In many cases, erection dysfunction did not require withdrawal of medication. Disappearance of erection problems among men with problems at baseline was common in all groups but greatest in the doxazosin group. Incidence of reported sexual problems in women was low in all treatment groups. In conclusion, long-term incidence of erection problems in treated hypertensive men is relatively low but is higher with chlorthalidone treatment. Effects of erection dysfunction with chlorthalidone appear relatively early and are often tolerable, and new occurrences after 2 years are unlikely. The rate of reported sexual problems in hypertensive women is low and does not appear to differ by type of drug. Similar incidence rates of erection dysfunction in placebo and most active drug groups caution against routine attribution of erection problems to antihypertensive medication.

Effect of acebutolol and propranolol on premature ventricular complexes.

A double-blind, randomized study comparing the efficacy of intravenous acebutolol with propranolol on frequent premature ventricular complexes (PVCs) in 24 patients is reported. Frequent PVCs were abolished or reduced by 75% or more in 10 of 12 patients (83%) given acebutolol and in 10 of 12 patients (83%) given propranolol. The therapeutic effect of acebutolol lasted for at least 1 hr in 4 of 12 patients (33%), for at least 3.5 hr in 3 of 12 patients (25%), and for at least 4 hr in 2 of 12 patients (17%). The effect of propranolol lasted for at least 1 hr in 6 of 12 patients (50%), for at least 3.5 hr in 4 of 12 patients (33%), and for at least 4 hr in 4 of 12 patients (33%). Hence, intravenous acebutolol and propranolol were equally effective.

Acebutolol in supraventricular arrhythmias.

The effect of intravenous acebutolol on supraventricular arrhythmias was evaluated in 20 patients, 5 with chronic obstructive pulmonary disease. A rapid ventricular rate in atrial fibrillation was slowed greater than 15% in all of 10 patients by acebutolol and in none of 5 patients by saline. A rapid ventricular rate in atrial flutter was slowed greater than 15% in all of 6 patients by acebutolol and in none of 3 patients by saline. Frequent premature atrial beats were abolished or reduced by greater than 75% in each of 2 patients by acebutolol and not in a patient by saline. Acebutolol converted multifocal atrial tachycardia to sinus rhythm in a patient. Digitalis-induced nonparoxysmal atrioventricular junctional tachycardia was not affected by saline but was abolished by acebutolol in a patient. Acebutolol was well tolerated in each of 5 patients with chronic obstructive pulmonary disease. Acebutolol is useful in the treatment of supraventricular arrhythmias.

Glucose and lipid metabolism during acebutolol and propranolol therapy of angina in nondiabetic patients.

The metabolic effects of acebutolol, a cardioselective beta-adrenergic blocker, and of propranolol, a nonselective beta blocker, were evaluated. Our subjects were 20 men with chronic stable angina; none had diabetes. An initial 4-wk, single-blind control phase was followed by two drug treatment periods, each a 3-wk double-blind titration phase (using increasing doses of acebutolol or propranolol), followed by a 5-wk double-blind maintenance phase. Metabolic studies were performed at the end of the control and maintenance phases. Propranolol induced elevation in basal serum glucose concentrations and both propranolol and acebutolol decreased glucose tolerance at 2.5 and 3 hr. There was no noticeable effect on insulin secretion by either drug. Neither propranolol nor acebutolol induced hyperlipidemia. There was a small decrease in total serum cholesterol after propranolol. Both drugs decreased low-density lipoprotein cholesterol. No effects were noted on the levels of serum triglycerides, high-density lipoprotein cholesterol, or free fatty acids.

Acebutolol and hydrochlorothiazide in essential hypertension.

Acebutolol (ABL) and hydrochlorothiazide (HCT) were compared in patients with mild to moderate essential hypertension and low or normal peripheral renin activity. ABL reduced mean supine blood pressure from 151/97 to 140/87 mm Hg and HCT reduced the mean supine blood pressure from 153/98 to 143/92 mm Hg. ABL reduced heart rate from 73 to 67 beats/min; during HCT therapy it rose from 74 to 77 beats/min. Although the same proportion of patients achieved normal diastolic pressures with ABL (11/19) and with HCT (10/19), tension-time indices were lower during ABL than during HCT therapy. The average daily dose was 621 mg of ABL and 168 mg of HCT. Stimulated peripheral renin activity increased with HCT and was the same or lower with ABL. ABL did not induce adverse effects on serum potassium or uric acid. ABL was as effective in lowering blood pressure HCT but induced larger reductions in tension-time index as a result of the lowerered heart rate.

Addition of acebutolol to diuretics in hypertension.

The effect of acebutolol as an antihypertensive beta receptor-blocking drug was evaluated in 15 patients that remained hypertensive while on diuretics. Observations were made in a small randomized double-blind trial in which the drug was compared to placebo and subsequently during a single-blind phase when the drug was given to those who had not responded to placebo. The dose range for acebutolol was 200 to 600 mg twice daily. Pretreatment plasma renin activity (PRA) and the response to intravenous saralasin infusion were assessed as predictors of the antihypertensive effect of acebutolol. None of six patients receiving placebo had a response of goal blood pressure or below; six of nine receiving acebutolol did respond (P less than 0.01). Acebutolol treatment induced reduction in diastolic pressure, heart rate, and PRA pooled from both phases of the study. There were no significant correlations between acebutolol therapy. Our data indicate that acebutolol is effective in diuretic-resistant hypertensive patients and that indices of the renin-angiotensin system are not predictors of the therapeutic response.

Circulatory effects of intravenous and oral acebutolol in acute myocardial infarction.

The hemodynamic dose-response effects of intravenous (25 and 50 mg) and oral (200 and 400 mg) acebutolol were compared in a randomized between-group study in men within 17 hours of an acute uncomplicated myocardial infarction. Six subjects were evaluated in each of the four groups. After a 1-hour control period, hemodynamic variables and plasma drug concentrations were determined at 15 (intravenous therapy only), 30, 60, 90, 120, and 240 minutes after dosing. At the doses studied, hemodynamic dose-response effects were not evident after either intravenous or oral acebutolol. In all groups acebutolol reduced systolic and mean systemic arterial pressure, heart rate, cardiac output, and stroke volume. Pulmonary artery occluded pressure and systemic vascular resistance were transiently increased. Maximum changes developed between 15 and 30 minutes after intravenous dosing and between 1 and 2 hours after oral dosing. However, there were substantial reductions in cardiac output (-0.7 L/min/m2; P less than 0.05) by 30 minutes after oral dosing. Effects lasted for 2 hours after intravenous dosing and for 4 hours after oral dosing. Our data confirm the hemodynamic safety of acebutolol after acute myocardial infarction. The relevance of the time-dependent hemodynamic differences between intravenous and oral initiation of beta-blockade to the overall goal of reducing myocardial oxygen requirements after acute coronary artery occlusion merits closer examination.

Effects of beta blockade with acebutolol on hypertension, hemodynamics, and fluid volume.

Eleven patients with essential hypertension were treated with the beta adrenergic blocker, acebutolol. Clinical, systemic, and regional hemodynamic and biochemical studies were performed before and after 4 wk of acebutolol therapy (average doses, 1,200 mg/day.) In 4 patients there was a reduction in mean arterial pressure greater than or equal to 10 mm Hg; there was none in the remainder. Regardless of the blood pressure response, the renin secretory index did not change. Although cardiac output did not change, renal blood flow fell (p less than 0.005) without relation to response of arterial pressure. Supine heart rate decreased (p less than 0.05), so also the responses to upright tilt (p less than 0.01) and isometric exercise (p less than 0.02). These results demonstrate that in those patients with a hypotensive response to acebutolol, the clinical effect was not related to reduced cardiac output or plasma renin activity, further adding to confusion on the mechanism of the lowering of elevated blood pressure by beta adrenergic blockade.

Acebutolol and left ventricular function: assessment by radionuclide angiography.

We assessed the effects of acebutolol, a cardioselective beta blocker, on global and regional left ventricular function in 26 patients with chronic angina pectoris. All patients underwent rest and maximal supine bicycle exercise radionuclide angiography while on placebo and oral acebutolol (400 mg three times a day). Resting ejection fraction on placebo was 51 +/- 3% and on acebutolol was 54 +/- 3% (p less than 0.05). No resting ejection fraction decreased greater than or equal to 7%. Only one patient (resting ejection fraction 28% on placebo and 21% on acebutolol) developed signs of fluid retention. Exercise nuclear studies on placebo revealed responses consistent with coronary artery disease (abnormal ejection fraction response to exercise and regional wall motion abnormalities) in 24 of 26 patients. Peak exercise ejection fraction was of the same order on placebo and acebutolol (51 +/- 3% and 54 +/- 3%, p = NS). In four patients the ejection fraction response to exercise became normal and in five patients all regional wall motion abnormalities became normal on acebutolol. Cardioselective beta blockade with acebutolol in effective antianginal doses is safe and may improve resting and exercise ventricular function.