0000000000747044
AUTHOR
K. Winter
Response of isolated human ventricular myocardium to cyclic AMP and its dibutyryl derivative.
The contractile responses to c-AMP and DB-c-AMP were studied in isolated electrically stimulated human papillary muscle strips. C-AMP (1×10−4 to 1×10−3 M) had no effect on contractile force in all of 6 human papillary muscle preparations studied. In contrast, DB-c-AMP (10−4 to 5×10−3 M) produced a concentration-dependent and reversible positive inotropic effect which was associated by a decrease in time to peak force and in relaxation time and which was not inhibited by 10−6 M propranolol. The possibility of a clinical applicability of DB-c-AMP is discussed.
Effect of serotonin uptake inhibition by zimelidine on hypothalamic-pituitary-adrenal activity
Plasma ACTH levels after oral ingestion of 2 g metyrapone at 24.00 hours in six healthy subjects were higher after pretreatment with zimelidine (300 mg) in comparison to placebo. Since zimelidine is a relatively selective serotonin reuptake inhibitor its action on hypothalamic-pituitary-adrenal (HPA) activity suggests that serotonin is a potent stimulator of ACTH release. The ratio of cortisol to 11-deoxycortisol was taken as a measure of 11-hydroxylase activity, which indicates biological activity of secreted ACTH. These cortisol/11-deoxycortisol ratios were significantly increased after zimelidine treatment, when compared to placebo. Both the ACTH response and the cortisol/11-deoxycortiso…
Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry
Abstract Background Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients’ clinical phenotypes and analyse the differential clinical course. Methods We performed a hierarchical cluster analysis based on Ward’s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results A total of 9363 were available for this analysis. We identified three …
Über den Einfluß von Dibutyryl-c-AMP auf die Kontraktionskraft des isolierten menschlichen Ventrikelmyokards
Cyclisches 3′,5′-AMP (c-AMP) soll am Warmbluterherzen neben den metabolischen auch die positiv inotropen Effekte der Katecholamine vermitteln (z. B. Sutherland et al., 1968). Es wurde als Stutze dieser Hypothese angesehen, das das Dibutyrylderivat des cyclischen 3′,5′-AMP (DB-c-AMP) an Herzmuskelpraparaten verschiedener Spezies positiv inotrop wirkt (Kukovetz und Poch, 1970; Skelton et al., 1970). Da diese Hypothese auch hinsichtlich des Wirkungsmechanismus der Katecholamine am menschlichen Herzen von Bedeutung sein kann, wurde gepruft, wie DB-c-AMP die Kontraktionskraft des menschlichen Herzmuskelgewebes beeinflust.
Effect of DB-c-AMP on mechanical characteristics of ventricular and atrial preparations of several mammalian species
Conflicting results exist about the influence of cyclic N6-2′-O-dibutyryl-AMP (DB-c-AMP) on myocardial contractile force. The present study was designed to examine whether the positive inotropic action of DB-c-AMP is restricted to certain model preparations or whether it can be assumed to represent a more general effect of the drug. Therefore, the effects of DB-c-AMP on myocardial force and on various parameters of the isometric contraction curve were examined in isolated electrically driven (0.5–2Hz) ventricular and atrial preparations of several mammalian species (cat, rabbit, calf, sheep, rat and guinea-pig). The following results were obtained: