Abstract 13538: Relaxin Mitigates a Substrate for Atrial Fibrillation in Spontaneously Hypertensive Rats
Atrial Fibrillation (AF), the most common arrhythmia, contributes significantly to morbidity and mortality. AF has been associated with hypertension, aging, and fibrosis. Studies have shown that Spontaneously Hypertensive Rat (SHR) hearts have higher levels of fibrosis, atrial tachycardia (AT) and AF. The exact mechanism of hypertensive inducible AF risk remains elusive; yet, studies have shown that increased fibrosis associated with hypertension can promote reentry. Drugs targeted at the underlying fibrotic substrate have claimed to be a new frontier in the management of AF. The study consisted of four groups of aged matched rats (9-12 months). These were SHR, normotensive Wistar Kyoto rats (WKY), SHR treated with 2 weeks of 450 μg/kg/day of Relaxin (RLX) (SHR+RLX), and SHR treated with 2 weeks of saline vehicle (SHR+V). These hearts were isolated and stained with PGH1 and Rhod-2 to map action potentials (AP) and intracellular Ca2+ transients (CaiT). The Right Atrium (RA) was paced using programmed stimulation. In SHR, a premature S2 induced sustained AF (n=5/5) whereas AF could not be induced in WKY (n=0/4) (p<0.01). SHR+RLX had a decreased incidence of inducible AF (n=1/6) (p<0.01 vs. SHR, SHR+V). Analysis of restitution kinetics (RK) for AP duration (APD) and CV revealed no differences between the different groups except for CV. SHR had significantly slower CV (p<0.01 vs WKY, SHR+RLX). In RLX treated SHR, collagen deposition reversed to control levels found in WKY hearts with an increase in metallo-proteinase 6, 9 levels and CV (p<0.01, SHR, SHR+V). Slower CV was attributed to higher atrial fibrosis levels in SHR and SHR+V (p<0.01 vs WKY, SHR+RLX). Western blots for connexin 43 (CX43) revealed significantly reduced phosphorylated CX43 in SHR (p<0.05 vs WKY) indicating lateralization of gap junctions. Our study provides compelling evidence that fibrosis, which is associated with chronic hypertension, is an important substrate for AF inducibility. RLX suppresses AF inducibility in SHR by improving CV through the reversal of fibrosis. Further studies are warranted to elucidate the effects of RLX on INa, CX 43, and intercellular coupling which can play a critical role in modulating CV.
- © 2012 by American Heart Association, Inc.