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No impact of sex and age on beta‐adrenoceptor‐mediated inotropy in human right atrial trabeculae
Author(s) -
Pecha Simon,
Geelhoed Bastiaan,
Kempe Romy,
Berk Emanuel,
Engel Andreas,
Girdauskas Evaldas,
Reichenspurner Hermann,
Ravens Ursula,
Kaumann Alberto,
Eschenhagen Thomas,
Schnabel Renate B.,
Christ Torsten
Publication year - 2021
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13564
Subject(s) - contractility , inotrope , medicine , beta (programming language) , cardiology , endocrinology , antagonist , receptor , computer science , programming language
Aim There is an increasing awareness of the impact of age and sex on cardiovascular diseases (CVDs). Differences in physiology are suspected. Beta‐adrenoceptors (beta‐ARs) are an important drug target in CVD and potential differences might have significant impact on the treatment of many patients. To investigate whether age and sex affects beta‐AR function, we analysed a large data set on beta‐AR‐induced inotropy in human atrial trabeculae. Methods We performed multivariable analysis of individual atrial contractility data from trabeculae obtained during heart surgery of patients in sinus rhythm (535 trabeculae from 165 patients). Noradrenaline or adrenaline were used in the presence of the beta 2 ‐selective antagonist (ICI 118 551, 50 nmol/L) or the beta 1 ‐selective antagonist (CGP 20712A, 300 nmol/L) to stimulate beta 1 ‐AR or beta 2 ‐AR respectively. Agonist concentration required to achieve half‐maximum inotropic effects (EC 50 ) was taken as a measure of beta‐AR sensitivity. Results Impact of clinical variables was modelled using multivariable mixed model regression. As previously reported, chronic treatment with beta‐blockers sensitized beta‐AR. However, there was no significant interaction between basal force, maximum force and beta‐AR sensitivity when age and sex were modelled continuously. In addition, there was no statistically significant effect of body mass index or diabetes on atrial contractility. Conclusion Our large, multivariable analysis shows that neither age nor sex affects beta‐AR‐mediated inotropy or catecholamine sensitivity in human atrial trabeculae. These findings may have important clinical implications because beta‐ARs, as a common drug target in CVD and heart failure, do not behave differently in women and men across age decades.