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PO3-3-5

TRPC3 channel inhibitor pyrazole-3 suppresses atrial fibrillation in rats with aorto-venocaval shunt as a pathological condition of chronic volume overload

[Speaker] Megumi Aimoto:1
[Co-author] Xin Cao:1, Yoshinobu Nagasawa:1, Akira Takahara:1
1:Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Japan

Purpose: Transient receptor potential canonical 3 (TRPC3) channel is one of the non-voltage gated Ca2+-permeable channels, acting as a sensor for a wide range of stimuli. Moreover, recent studies have demonstrated that the channels densely interact with cardiovascular signaling. In this study, we assessed antiarrhythmic effect of TRPC3 channel inhibitor Pyrazole-3 (Pyr3) on the rat atria chronically exposed to volume overload by abdominal aorto-venocaval shunt (AVS).
Methods: AVS was created under the anesthesia, and Pyr3 was intraperitoneally administered using an osmotic minipump throughout the experiment. Morphological and electrophysiological assessments were performed 3 months after the surgery. Rats were divided into 3 groups; namely, sham-operated group (n=5), AVS group (n=5), and AVS+Pyr3 group (n=5).
Results: AF was induced with high producibility using burst pacing to the atrium. AF lasted for 349 s in the AVS group, which was about 40 times longer than that in sham-operated group (8 s). The duration of AF in the AVS+Pyr3 group (42 s) was shorter than that in the AVS group. There was no significant difference in the atrial effective refractory period among the 3 groups. The duration of P wave of the ECG, roughly reflecting intra-atrial conduction time, was 26 ms in the AVS group, which was longer than that in the sham-operated group (17 ms). The P wave duration in the AVS+Pyr3 group (22 ms) was shorter than that in the AVS group. The atrial weights in the AVS group were about 4.3 times greater than that in the sham-operated group. The atrial weights in the AVS+Pyr3 group were less great than those in the AVS group.
Conclusion: Pyr3 exerted antiarrhythmic actions in the animal model that can induce sustained AF. The results may suggest that TRPC3 channel could be closely associated with atrial remodeling processes during the chronic volume overload.

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