{"title":"Beneficial effects of doxycycline on atrial electrical remodelling in a rat model of atrial fibrillation.","authors":"Kai Zhang, Zuowang Ma, Yu Yang, Guangping Li","doi":"10.1080/00015385.2025.2500888","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Previous studies showed that doxycycline (Dox) can attenuate chronic intermittent hypoxia (CIH)-induced atrial fibrosis in rats. On this basis, we further investigated the effects of Dox on CIH-induced atrial electrical remodelling.</p><p><strong>Methods: </strong>Rats were randomised into 3 groups: Control group, CIH group, and CIH with Dox treatment (CIH-D) group (<i>n</i> = 30). CIH and CIH-D rats were subjected to CIH 8 h/d for 6 weeks. After collecting the basic parameters of the rats, atrial fibrillation (AF) inducibility, conduction inhomogeneity, and epicardial conduction velocity were examined by <i>in vitro</i> cardiac electrophysiology experiments. The expression levels of ion channel subunits in the atrium were detected by Western blotting. Whole-cell patch clamp experiments were used to recorded action potential (AP), I<sub>Ca-L</sub>, I<sub>to</sub>, and the kinetic parameters.</p><p><strong>Results: </strong>Compared to the Control rats, CIH rats showed increased AF inducibility, conduction inhomogeneity, and expression levels of p-RyR2, p-CaMKII, K<sub>v</sub>11.1, K<sub>ir</sub>2.3, K<sub>Ca</sub>3.1, whereas the epicardial conduction velocity, I<sub>Ca-L</sub>, I<sub>to</sub>, and expression levels of Ca<sub>v</sub>1.2, K<sub>v</sub>1.5, K<sub>v</sub>4.3 were decreased. Dox-treatment significantly improved the expression levels of K<sub>v</sub>1.5, K<sub>v</sub>4.3 and K<sub>ir</sub>2.3 in CIH-D rats.</p><p><strong>Conclusion: </strong>CIH caused atrial electrical remodelling in our rats, which was improved by Dox treatment. These changes indicated the potential effects of Dox in AF.</p>","PeriodicalId":6979,"journal":{"name":"Acta cardiologica","volume":" ","pages":"1-11"},"PeriodicalIF":2.1000,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta cardiologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00015385.2025.2500888","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Previous studies showed that doxycycline (Dox) can attenuate chronic intermittent hypoxia (CIH)-induced atrial fibrosis in rats. On this basis, we further investigated the effects of Dox on CIH-induced atrial electrical remodelling.
Methods: Rats were randomised into 3 groups: Control group, CIH group, and CIH with Dox treatment (CIH-D) group (n = 30). CIH and CIH-D rats were subjected to CIH 8 h/d for 6 weeks. After collecting the basic parameters of the rats, atrial fibrillation (AF) inducibility, conduction inhomogeneity, and epicardial conduction velocity were examined by in vitro cardiac electrophysiology experiments. The expression levels of ion channel subunits in the atrium were detected by Western blotting. Whole-cell patch clamp experiments were used to recorded action potential (AP), ICa-L, Ito, and the kinetic parameters.
Results: Compared to the Control rats, CIH rats showed increased AF inducibility, conduction inhomogeneity, and expression levels of p-RyR2, p-CaMKII, Kv11.1, Kir2.3, KCa3.1, whereas the epicardial conduction velocity, ICa-L, Ito, and expression levels of Cav1.2, Kv1.5, Kv4.3 were decreased. Dox-treatment significantly improved the expression levels of Kv1.5, Kv4.3 and Kir2.3 in CIH-D rats.
Conclusion: CIH caused atrial electrical remodelling in our rats, which was improved by Dox treatment. These changes indicated the potential effects of Dox in AF.
期刊介绍:
Acta Cardiologica is an international journal. It publishes bi-monthly original, peer-reviewed articles on all aspects of cardiovascular disease including observational studies, clinical trials, experimental investigations with clear clinical relevance and tutorials.