Effects of different beta adrenoceptor ligands in mice with permanent occlusion of the left anterior descending coronary artery.

1. We have studied the effects of three betaAR ligands (carvedilol, alprenolol, and ICI-118551) with different pharmacological profiles and negative efficacy at the beta2AR on cardiac in vivo, in vitro, biochemical and gene expression parameters in mice with permanent occlusion of the left anterior descending coronary artery. 2. Cardiac in vivo parameters were determined using Doppler studies. Mitral-wave E peak velocity (EPV) and aortic peak velocity (AoPV) decreased in the first 2 weeks postocclusion. After 3 weeks of drug treatment, EPV was improved in the carvedilol group to preocclusion values; however, a further reduction in EPV in the alprenolol and control permanent occlusion group was measured and there was no change after ICI-118551 treatment. AoPV was unchanged between weeks 2 and 5 in all groups. 3. The left atria were isolated to record isometric tension responses to isoprenaline. Permanent occlusion significantly reduced the maximum isoprenaline response to 30% of control and carvedilol increased the maximum response to isoprenaline significantly to 60%. 4. The biochemical and gene expression studies revealed different effects of the three betaAR ligands. Most notably, carvedilol reduced gene expression of myosin heavy chain beta. 5. These results indicate that chronic treatment with carvedilol is beneficial in a mouse model of myocardial damage resulting from ischaemia. We hypothesise that these beneficial effects of the drug may be because of the negative efficacy at the beta2AR, combined with beta1AR antagonism.

One doctor's 25-year experience of beta-blocker treatment to the same group of hypertensive women.

OBJECTIVE: To assess the importance of long-term doctor-patient relationship, and to assess the effect of long-term treatment with beta-blockers of hypertensive women. DESIGN: A 25-year follow-up study of hypertensive women, compared with participants in a prospective population study of women of the same age. SETTING: Gothenburg, Sweden. SUBJECTS: 57 hypertensive women and 1462 participants in the population study. RESULTS: The women's blood pressure was well-controlled over the years, and no serious side-effects occurred. There was no increased mortality in these groups of hypertensive women compared with women in the general population of the same age. CONCLUSIONS: The favourable effects over the years with respect to the management of blood pressure and survival indicate the beneficial effect of a stable doctor-patient relationship and the beneficial long-term effect of beta-blockers as a base for antihypertensive treatment.

Modalidades terapêuticas na doença de Basedow-Graves / Therapeutical approaches in Basedow-Graves disease

Neste artigo säo analisadas as três grandes modalidades terapêuticas do hipertireoidismo - o tratamento clínico, o radioiodo e a cirurgia -, discutindo-se detalhadamente cada uma delas, enfocando seus mecanismos de açäo, vantagens e desvantagens, principais indicaçöes e contra indicaçöes. A abordagem terapêutica também será analisada em grupos especiais como neonatos, crianças e adolescentes, gestantes e idosos

Continuous alprenolol infusion for control of hypertension in the acute stage of ruptured intracranial aneurysms.

The clinical benefits and hemodynamic effects of continuous alprenolol infusion for control of hypertension in the acute stage of ruptured cerebral aneurysms were investigated. Twenty-five patients manifesting systemic hypertension (greater than 160/100 mmHg) were treated with alprenolol, a beta-adrenergic antagonist, phentolamine, an alpha-adrenergic antagonist, and trimethaphan camsilate, a ganglionic blocker, given intravenously. All drugs decreased the mean arterial blood pressure significantly. However, alprenolol decreased the heart rate and cardiac index while phentolamine increased them. Alprenolol also decreased arterial catecholamine and renin activity, but caused no change in central venous pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, and systemic vascular resistance. The results indicate the usefulness of continuous alprenolol infusion for the control of acute hypertension in hemorrhagic cerebrovascular disease. The mode of action of alprenolol is also discussed.

The long-term effect of alprenolol on plasma apolipoproteins A-I and B.

The concentration of lipids, lipoproteins and apolipoprotein A-I and B was measured in the plasma of 33 patients, enrolled in a double-blind, controlled trial of alprenolol in myocardial infarction, after one year on the study medication and again after 6 months off the medication. Sixteen patients received 200 mg alprenolol twice daily and 17 received placebo. There were no statistically significant differences between the parameters in the two groups after one year on medication. However, when medication was stopped, the ratio of apolipoprotein B to apolipoprotein A-I fell by 9% in the alprenolol group and increased by 2% in the placebo group. This difference was statistically significant. Our results suggest that alprenolol, a beta-blocker with weak intrinsic sympathomimetic effect, has slight effects on plasma lipoproteins. These effects were apparent only by measurements of apolipoproteins.

Decreased plasma concentrations and clinical effects of alprenolol during combined treatment with pentobarbitone in hypertension.

The antihypertensive effect of alprenolol has been studied before, during and after additional pentobarbitone treatment. The combined alprenolol-pentobarbitone treatment significantly decreased alprenolol levels by 59% and 4-hydroxyalprenolol by 24%. The effect was significant after three doses and declined over 4-5 days after pentobarbitone withdrawal. The decreased alprenolol plasma levels were associated with increased pulse rate (6%), and systolic (8%) and diastolic (9%) blood pressure. The inhibition of exercise tachycardia by alprenolol was reduced by 18% at the end of pentobarbitone treatment compared to initial monotherapy with alprenolol. The interaction is probably clinically important in those patients with hypertension and angina pectoris that are treated with barbiturates and alprenolol.

Anti-arrhythmic effect of nadolol in experimental arrhythmias: comparison with propranolol and alprenolol.

The effects of nadolol on experimental arrhythmias were investigated and compared with those of propranolol and alprenolol. The arrhythmias were induced by either ouabain, holothane plus adrenaline or acute coronary occlusion in anesthetized dogs. All three beta-blocking drugs in a dose range of 10 to 200 micrograms/kg inhibited halothane plus adrenaline-induced arrhythmias. These drugs also attenuated coronary occlusion-induced ventricular arrhythmias as well as other electrical abnormalities such as electrical alternation and conduction delay. Among the three drugs, nadolol was the most potent in suppressing both types of arrhythmias. Contrary to the potent effects on these arrhythmias, nadolol was ineffective against ouabain-induced arrhythmias even in a dose of 3 mg kg, while propranolol and alprenolol were significantly effective in a dose of 100 micrograms/kg. It is probable that the anti-arrhythmic effect of nadolol is exclusively due to its beta-blocking activity.

The effect of alprenolol on serum myoglobin levels in acute myocardial infarction.

In a group of 37 patients with definite acute myocardial infarction (AMI) allocated to treatment with either alprenolol (n = 20) or placebo (n = 17) serial determinations of concentrations in serum of myoglobin (S-Mb), creatine kinase (S-CK), aspartate aminotransferase (S-ASAT) and lactate dehydrogenase (S-LDH) were performed. The median peak levels of S-Mb, S-CK and S-LDH were significantly (P less than 0.05) lower among patients treated with alprenolol. The median of the estimated infarct size based on S-CK curves was also significantly (P less than 0.01) lower in the alprenolol group. There was no significant difference between the estimated infarct size based on S-Mb values in the two groups. It is concluded that the present study provides indirect evidence for the assumption that early beta-blockade in AMI can reduce infarct size.

Long-term alprenolol treatment affects serum T4, T3 and rT3 in euthyroid patients with ischaemic heart disease.

After treatment with alprenolol for 1 year, serum 3,3',5'-triiodothyronine (rT3) was significantly increased (P less than 0.01) in a group (n = 20) of euthyroid subjects compared to a control group (n = 20) given placebo. All subjects had definite or suspected myocardial infarction one year previously. Serum thyroxine (T4), free T3 index (FT4I), serum 3,5,3'-triiodothyronine, (T3) and free T3 index (FT3I) were not significantly different in the two groups. Alprenolol and placebo were gradually withdrawn over 14 days. On the first day after withdrawal a significant decrease in serum rT3 in the alprenolol treated group was the only change observed. Fourteen days after withdrawal a significant fall in serum T4, FT4I, rT3 and a rise in serum T3 and FT3I was found in the alprenolol treated group. Six months after withdrawal the only further change observed in the alprenolol treated group was an increase in T3 and FT3I. No changes occurred in the placebo treated group in any of the hormones studied. The results are consistent with a direct effect of long-term alprenolol treatment on the peripheral levels of serum T4, T3 and rT3 in euthyroid subjects. The changes in the thyroid hormones after withdrawal further indicate withdrawal of a permanent inhibition of 5'deiodinase during long-term treatment with alprenolol in euthyroid subjects.