Resting membrane potential is less negative in trabeculae from right atrial appendages of women, but action potential duration does not shorten with age

https://doi.org/10.1016/j.yjmcc.2023.01.006Get rights and content

Highlights

  • We investigated the impact of clinical variables on human atrial action potential in a large dataset

  • The higher probability to develop AF at advanced age cannot be explained by a shortening in right atrial tissue

  • Less negative RMP and lower upstroke velocity might contribute to lower incidence of AF in women

Abstract

Aims

The incidence of atrial fibrillation (AF) increases with age. Women have a lower risk. Little is known on the impact of age, sex and clinical variables on action potentials (AP) recorded in right atrial tissue obtained during open heart surgery from patients in sinus rhythm (SR) and in longstanding AF. We here investigated whether age or sex have an impact on the shape of AP recorded in vitro from right atrial tissue.

Methods

We performed multivariable analysis of individual AP data from trabeculae obtained during heart surgery of patients in SR (n = 320) or in longstanding AF (n = 201). AP were recorded by sharp microelectrodes at 37 °C at 1 Hz. Impact of clinical variables were modeled using a multivariable mixed model regression.

Results

In SR, AP duration at 90% repolarization (APD90) increased with age. Lower ejection fraction and higher body mass index were associated with smaller action potential amplitude (APA) and maximum upstroke velocity (Vmax). The use of beta-blockers was associated with larger APD90. In tissues from women, resting membrane potential was less negative and APA as well as Vmax were smaller. Besides shorter APD20 in elderly patients, effects of age and sex on atrial AP were lost in AF.

Conclusion

The higher probability to develop AF at advanced age cannot be explained by a shortening in APD90. Less negative RMP and lower upstroke velocity might contribute to lower incidence of AF in women, which may be of clinical relevance.

Introduction

Atrial fibrillation (AF) is the most common rhythm disorder and associated with high comorbidity and increased mortality risk [1]. Research in recent years yielded detailed information about epidemiology and comorbidities affecting AF [2]. The incidence of AF increases with age, and women are at lower risk of developing the disease [1,3,4]. Many classical cardiovascular risk factors and comorbidities, e.g. heart failure, myocardial infarction, sleep disordered breathing, are known to affect AF [4]. However, their impact on atrial electrophysiology remains unclear. A more detailed understanding of the underlying pathophysiological mechanisms would be a further step towards improving personalized medicine [2]. Therefore, we set out to investigate retrospectively the impact of clinical variables on action potentials (AP) recorded in right atrial tissue obtained during open heart surgery from patients in sinus rhythm (SR) and in persistent atrial fibrillation (AF).

Section snippets

Human tissue samples

The study followed the declaration of Helsinki and all patients gave written informed consent. All investigations were approved by the Medical Faculty Ethics Committee of the Technical University Dresden; approval number EK 114082202. Each patient gave written, informed consent. Clinical parameters were collected from the medical records of patients and analyzed after anonymisation. Part of data were previously used for a preliminary analysis on sex effects on AP [5]. Some data were used for

Results

We analyzed data from 521 patients undergoing open heart surgery. 320 patients with SR and 201 patients with longstanding persistent AF were included in this retrospective analysis.

Principal findings

In our large data set we investigated the impact of clinical variables on human atrial AP by multivariable analyses. We found only moderate effects of age on APD90, which we assume cannot explain the steep increase in AF prevalence with age. However, there were clear sex-related differences that could be relevant for the lower incidence of AF in women.

Clinical context: age

The higher likelihood of AF observed in the elderly suggests distinct electrophysiological changes that facilitate the occurrence of AF. Effects

Conclusions

In humans, the increase in AF with age cannot be explained by a shortening in APD. The lower incidence of AF in women associates with less negative RMP and reduced sodium channel function. One may speculate whether pharmacological inhibition of currents regulating RMP could be helpful to prevent reoccurrence of AF.

The following are the supplementary data related to this article.

. Mean and standard deviations of action potential duration at 20, 50, and 90% of repolarization (APD90, APD50 and APD20

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. RBS has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under the grant agreement No 648131, from the European Union's Horizon 2020 research and innovation programme under the grant agreement No 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK) (81Z1710103); German

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Declaration of Competing Interest

SP has received lecture fees and advisory board fees from Medtronic and Philips Healthcare outside this work. RBS has received lecture fees and advisory board fees from BMS/Pfizer outside this work.

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