Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Yoshinobu Hara¹  Takafumi Katsumura¹  Hiroyuki Sakagami¹  Ryo Nishinarita²  Gen Matsuura²  Tazuru Igarashi²  Jun Oikawa²  Jun Kishihara²  Tetsuro Sato²  Naruya Ishizue²  Junya Ako²  Yuki Arakawa²  Shuhei Kobayashi²  Ai Horiguchi²  Daiki Saito²  Hidehira Fukaya²  Shinichi Niwano²  Yuki Shirakawa²  Hironori Nakamura³  Tomoharu Yoshizawa⁴  Akira Satoh⁵  Hiroe Niwano⁶ 

[1] Department of Anatomy Kitasato University School of Medicine Sagamihara Japan;Department of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara Japan;Department of Cardiovascular Medicine Nerima Hikarigaoka Hospital Nerima Japan;Department of Cardiovascular Medicine Yamato Municipal Hospital Yamato Japan;Department of Cardiovascular Medicine Yokohama Asahi Central Hospital Yokohama Japan;Department of Education Tamagawa University, College of Education Machida Japan;

关键词: atrial fibrillation;    atrial remodeling;    canagliflozin;    oxidative stress;    sodium–glucose cotransporter 2 inhibitor;   

DOI  :  10.1161/JAHA.119.017483

来源: DOAJ

【 摘 要 】

Background Recent clinical trials have demonstrated the possible pleiotropic effects of SGLT2 (sodium–glucose cotransporter 2) inhibitors in clinical cardiovascular diseases. Atrial electrical and structural remodeling is important as an atrial fibrillation (AF) substrate. Methods and Results The present study assessed the effect of canagliflozin (CAN), an SGLT2 inhibitor, on atrial remodeling in a canine AF model. The study included 12 beagle dogs, with 10 receiving continuous rapid atrial pacing and 2 acting as the nonpacing group. The 10 dogs that received continuous rapid atrial pacing for 3 weeks were subdivided as follows: pacing control group (n=5) and pacing+CAN (3 mg/kg per day) group (n=5). The atrial effective refractory period, conduction velocity, and AF inducibility were evaluated weekly through atrial epicardial wires. After the protocol, atrial tissues were sampled for histological examination. The degree of reactive oxygen species expression was evaluated by dihydroethidium staining. The atrial effective refractory period reduction was smaller (P=0.06) and the degree of conduction velocity decrease was smaller in the pacing+CAN group compared with the pacing control group (P=0.009). The AF inducibility gradually increased in the pacing control group, but such an increase was suppressed in the pacing+CAN group (P=0.011). The pacing control group exhibited interstitial fibrosis and enhanced oxidative stress, which were suppressed in the pacing+CAN group. Conclusions CAN and possibly other SGLT2 inhibitors might be useful for preventing AF and suppressing the promotion of atrial remodeling as an AF substrate.

【 授权许可】

Unknown