No impact of sex and age on beta-adrenoceptor-mediated inotropy in human right atrial trabeculae

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Simon Pecha - , University Hospital Hamburg Eppendorf (Author)
  • Bastiaan Geelhoed - , Deutsches Zentrum für Herz-Kreislaufforschung (DZHK) (Author)
  • Romy Kempe - , Structure and Materials Mechanics Research Institute at the Dresden University of Technology (SWM) (Author)
  • Emanuel Berk - , University Hospital Hamburg Eppendorf (Author)
  • Andreas Engel - , Institute of Forensic Medicine, University Hospital Hamburg Eppendorf (Author)
  • Evaldas Girdauskas - , University Hospital Hamburg Eppendorf (Author)
  • Hermann Reichenspurner - , University Hospital Hamburg Eppendorf (Author)
  • Ursula Ravens - , University of Freiburg (Author)
  • Alberto Kaumann - , University of Murcia (Author)
  • Thomas Eschenhagen - , University Hospital Hamburg Eppendorf (Author)
  • Renate B Schnabel - , Deutsches Zentrum für Herz-Kreislaufforschung (DZHK) (Author)
  • Torsten Christ - , University Hospital Hamburg Eppendorf (Author)

Abstract

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 beta2 -selective antagonist (ICI 118 551, 50 nmol/L) or the beta1 -selective antagonist (CGP 20712A, 300 nmol/L) to stimulate beta1 -AR or beta2 -AR respectively. Agonist concentration required to achieve half-maximum inotropic effects (EC50 ) 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.

Details

Original languageEnglish
Article numbere13564
Pages (from-to)e13564
JournalActa Physiologica Scandinavica
Volume231
Issue number3
Publication statusPublished - Mar 2021
Peer-reviewedYes

External IDs

Scopus 85094193185
ORCID /0000-0003-3021-1338/work/142251879

Keywords

Sustainable Development Goals

Keywords

  • Adrenergic beta-Antagonists/pharmacology, Female, Heart Atria, Human Rights, Humans, Male, Myocardial Contraction, Norepinephrine, Receptors, Adrenergic, beta-2