Anti-atrial Fibrillatory Effects of the TRPC3 Channel Inhibitor Pyrazole-3 in Rats with Atrial Enlargement Induced by Chronic Volume Overload

The effect of transient receptor potential canonical-3 (TRPC3) channel inhibitor pyrazole-3 (Pyr3) on the stability of atrial fibrillation (AF) was analyzed in a rat model of chronic volume overload. Male Wistar rats underwent aorto-venocaval shunt (AVS) surgery and received Pyr3 treatment intraperitoneally for 12 weeks. Morphological and electrophysiological assessments were performed at the end of the treatment period. Longer P-wave duration, atrial conduction time, and AF duration, in addition to greater atrial tissue weight, were detected in AVS rats compared with sham rats. Chronic Pyr3 administration prevented AVS-induced prolongation of P-wave duration and atrial conduction time, partially prevented atrial weight increase, and abbreviated AVS-induced prolongation of AF duration to similar levels as those in sham rats, without affecting the atrial effective refractory period. These results suggest that the TRPC3 inhibitor Pyr3 can ameliorate sustained AF associated with chronic volume overload by improving atrial conduction defects in AVS rats. Pharmacological inhibition of TRPC3 channels by Pyr3 thus represents a promising therapeutic strategy for preventing AF development related to structural modeling.