To characterize the pattern of pacemaker dominance in the ventricular specialized conduction system (VSCS), escape ventricular pacemakers were localized and quantified in vivo and in virto, in normal hearts and in hearts 24 hours after myocardial infarction. Excape pacemaker foci were localized in vivo during vagally induced atrial arrest by means of electrograms recorded from the His bundle and proximal bundle branches and standard electrocardiographic limb leads. The VSCS was isolated using a modified Elizari preparation or preparations of each bundle branch. Peacemakers were located by extra- and intracellular recordings. Escape pacemaker foci in vivo were always in the proximal conduction system, usually the left bundle branch. The rate was 43+/-11 (mean+/-SD) beats/min. After beta-adrenergic blockade, the mean rate fell to 31+/-10 beats/min, but there were no shifts in pacemaker location. In the infarcted hearts, pacemakers were located in the peripheral left bundle branch. The mean rate was 146+/-20 beats/min. In isolated normal preparations, the dominant pacemakers usually were in the His bundle, firing at a mean rate of 43+/-10 beats/min. The rates of pacemakers diminished with distal progression. In infarcted hearts, the pacemakers invariably were in the infarct zone. The mean firing rates were not influenced by beta-adrenergic blockade. The results indicate that the dominant pacemakers are normally in the very proximal VSCS, but after myocardial infarction pacemaker dominance is shifted into the infarct. Distribution of pacemaker dominance is independent of sympathetic influence. (+info)
Constitutively active mutants of the beta1-adrenergic receptor.
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We provide the first evidence that point mutations can constitutively activate the beta(1)-adrenergic receptor (AR). Leucine 322 of the beta(1)-AR in the C-terminal portion of its third intracellular loop was replaced with seven amino acids (I, T, E, F, C, A and K) differing in their physico-chemical properties. The beta(1)-AR mutants expressed in HEK-293 cells displayed various levels of constitutive activity which could be partially inhibited by some beta-blockers. The results of this study might have interesting implications for future studies aiming at elucidating the activation process of the beta(1)-AR as well as the mechanism of action of beta-blockers. (+info)
An eighteen months' study of the clinical response to metoprolol, a selective beta1-receptor blocking agent, in patients with angina pectoris.
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Following an initial dose response study, metoprolol, a selective beta1-receptor blocking agent, was compared with equipotent dosages of propanolol in a double blind cross-over study, including exercise tolerance tests, on fourteen patients with angina pectoris. Long term therapy with metoprolol then followed until the seventy-second week. Patients performed 8% more total work on metoprolol with 15% more work recorded up to the onset of S-T depression, in comparison with propranolol. In the long term, ther was no significant difference in work performed when the daily dosage of metoprolol was changed from a q.i.d. to a b.d. regime. Metoprolol was shown to be an effective anti-anginal compound with good tolerance and safety, with gradual improvement in underlying myocardial ischaemia during long term treatment. (+info)
Abnormal lymphocyte function is secondary to drug-induced autoimmunity.
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Abnormal lymphocyte function has been frequently reported in patients with connective tissue diseases but its significance has been uncertain. Sequential studies of lymphocyte function were carried out in patients receiving the beta-adrenergic blocking drug practolol (Eraldin) both before and during the development of autoimmune complications. No evidence was obtained that abnormal lymphocyte function presaged the onset of autoimmunity, and when these tests did show deficient responses these could be correlated with disease activity in general. (+info)
Practolol and ocular toxicity. Antibodies in serum and tears.
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Serological studies in 22 patients presenting with ocular disease attributable to dosage with the beta-blocking agent practolol revealed a raised incidence of antinuclear antibodies. There was also a marginal increase in the incidence of antibodies to smooth muscle in the more severely affected individuals but the incidence of ther autoantibodies and levels of IgG, IgA, and IgM were within normal limits. Semi-quantitative analysis of tears from 14 of the patients showed absence or near absence in the more severely affected patients of secretory IgA, which is indicative of damage to the lacrimal gland. Other immunological parameters in the tears were normal. (+info)
Untoward effects associated with practolol: demonstration of antibody binding to epithelial tissue.
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An antibody which sticks to the intercellular region of xenogenic epidermal tissue has been shown by indirect immunofluorescence to be present in the serum of patients with practolol-induced eye damage. These antibodies and those found in patients with pemphigus were compared for their ability to bind to isolated epidermal cells. Binding was achieved only with the pemphigus antibody, which suggests that it may have a different specificity from the antibody associated with practolol-induced eye damage. (+info)
Beta blockade in lithium tremor.
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Practolol, propranolol, and placebo have been tested on an objective test of lithium induced tremor. Both beta-blocking agents produced significantly more tremor than the placebo. It is argued that lithium induced tremor is closer to essential than to physiological tremor. (+info)
Untoward effects associated with practolol administration: oculomucocutaneous syndrome.
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Keratoconjunctivitis sicca, conjunctival scarring, fibrosis, metaplasia, and shrinkage developed in 27 patients as an adverse reaction to practolol. Rashes, nasal and mucosal ulceration, fibrous or plastic peritonitis, pleurisy, cochlear damage, and secretory otitis media also occurred in some cases. Three patients suffered profound visual loss though most retained good vision. Symptoms and signs improved on withdrawal of the drug, but reduction of tear secretion persisted in most patients. (+info)