Relaxin suppresses atrial fibrillation in aged rats by reversing fibrosis and upregulating Na+ channels.

Heart Rhythm

University of Pittsburgh School of Medicine, Heart and Vascular Institute, Pittsburgh, Pennsylvania,; University of Pittsburgh Department of Bioengineering, and the McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania. Electronic address:

Published: April 2016

Background: Atrial fibrillation (AF) contributes significantly to morbidity and mortality in elderly patients and has been correlated with enhanced age-dependent atrial fibrosis. Reversal of atrial fibrosis has been proposed as therapeutic strategy to suppress AF.

Objective: To test the ability of relaxin to reverse age-dependent atrial fibrosis and suppress AF.

Methods: Aged F-344 rats (24 months old) were treated with subcutaneous infusion of vehicle or relaxin (0.4 mg/kg/day) for 2 weeks. Rat hearts were excised, perfused on a Langendorff apparatus, and stained with voltage and Ca(2+) indicator dyes. Optical mapping and programmed electrical stimulation was used to test arrhythmia vulnerability and changes in electrophysiological characteristics. Changes in protein expression and Na(+) current density (INa) were measured by tissue immunofluorescence and whole-cell patch clamp technique.

Results: In aged rats, sustained AF was readily induced with a premature pulse (n = 7/8) and relaxin treatment suppressed sustained AF by a premature impulse or burst pacing (n = 1/6) (P < .01). Relaxin significantly increased atrial action potential conduction velocity and decreased atrial fibrosis. Relaxin treatment increased Nav1.5 expression (n = 6; 36% ± 10%) and decreased total collagen and collagen I (n = 5-6; 55%-66% ± 15%) in aged atria (P < .05) and decreased collagen I and III and TGF-β1 mRNA (P < .05). Voltage-clamp experiments demonstrated that relaxin treatment (100 nM for 2 days) increased atrial INa by 46% ± 4% (n = 12-13/group, P < .02).

Conclusion: Relaxin suppresses AF through an increase in atrial conduction velocity by decreasing atrial fibrosis and increasing INa. These data provide compelling evidence that relaxin may serve as an effective therapy to manage AF in geriatric patients by reversing fibrosis and modulating cardiac ionic currents.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801709PMC
http://dx.doi.org/10.1016/j.hrthm.2015.12.030DOI Listing

Publication Analysis

Top Keywords

atrial fibrosis
20
relaxin treatment
12
atrial
10
relaxin
9
relaxin suppresses
8
atrial fibrillation
8
aged rats
8
reversing fibrosis
8
age-dependent atrial
8
increased atrial
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!