Chronic volume overload and aldosterone provide arrhythmogenic substrates in the rat atria via potentiation of proarrhythmic responses to cholinergic activation

Abstract

Cholinergic responses of atria have been known to play an important role in vagally-mediated atrial fibrillation (AF). We investigated influence of chronic volume overload and long-term exposure to higher plasma levels of aldosterone on electrophysiological responses to cholinergic activation in the rat atria. Rats were divided into three groups based on receiving sham surgery, aorto-venocaval shunt (AVS) surgery to deliver chronic volume overload, or AVS plus aldosterone administration (1.0 μg/h, i.p.) using an osmotic minipump. Four weeks later of the AVS surgery, hypertrophy as well as prolongation of atrial effective refractory period (AERP) were observed in the isolated heart. Carbachol at 0.1 and 1.0 μM shortened AERP, reflecting proarrhythmic response, which was potentiated by AVS and further enhanced by AVS plus aldosterone. Carbachol increased intra-atrial conduction velocity, reflecting antiarrhythmic response, which was also potentiated by AVS operation but attenuated by AVS plus aldosterone. These results suggest that chronic volume overload and aldosterone provide arrhythmogenic substrates in the rat atria via potentiation of proarrhythmic responses to cholinergic activation. Attenuation of antiarrhythmic response by AVS plus aldosterone may also modify the generation of arrhythmogenic substrates in the rat atria.