Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model
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 pr...
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| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.119.017483 |
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| author | Ryo Nishinarita Shinichi Niwano Hiroe Niwano Hironori Nakamura Daiki Saito Tetsuro Sato Gen Matsuura Yuki Arakawa Shuhei Kobayashi Yuki Shirakawa Ai Horiguchi Naruya Ishizue Tazuru Igarashi Tomoharu Yoshizawa Jun Oikawa Yoshinobu Hara Takafumi Katsumura Jun Kishihara Akira Satoh Hidehira Fukaya Hiroyuki Sakagami Junya Ako |
| author_facet | Ryo Nishinarita Shinichi Niwano Hiroe Niwano Hironori Nakamura Daiki Saito Tetsuro Sato Gen Matsuura Yuki Arakawa Shuhei Kobayashi Yuki Shirakawa Ai Horiguchi Naruya Ishizue Tazuru Igarashi Tomoharu Yoshizawa Jun Oikawa Yoshinobu Hara Takafumi Katsumura Jun Kishihara Akira Satoh Hidehira Fukaya Hiroyuki Sakagami Junya Ako |
| author_sort | Ryo Nishinarita |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T11:05:18Z |
| format | Article |
| id | doaj.art-ad5e849bb10448688603fcd627c34aea |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-18T11:05:18Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-ad5e849bb10448688603fcd627c34aea2022-12-21T21:10:08ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-01-0110210.1161/JAHA.119.017483Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation ModelRyo Nishinarita0Shinichi Niwano1Hiroe Niwano2Hironori Nakamura3Daiki Saito4Tetsuro Sato5Gen Matsuura6Yuki Arakawa7Shuhei Kobayashi8Yuki Shirakawa9Ai Horiguchi10Naruya Ishizue11Tazuru Igarashi12Tomoharu Yoshizawa13Jun Oikawa14Yoshinobu Hara15Takafumi Katsumura16Jun Kishihara17Akira Satoh18Hidehira Fukaya19Hiroyuki Sakagami20Junya Ako21Department of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Education Tamagawa University, College of Education Machida JapanDepartment of Cardiovascular Medicine Nerima Hikarigaoka Hospital Nerima JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Yamato Municipal Hospital Yamato JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Anatomy Kitasato University School of Medicine Sagamihara JapanDepartment of Anatomy Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Yokohama Asahi Central Hospital Yokohama JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Anatomy Kitasato University School of Medicine Sagamihara JapanDepartment of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara JapanBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.119.017483atrial fibrillationatrial remodelingcanagliflozinoxidative stresssodium–glucose cotransporter 2 inhibitor |
| spellingShingle | Ryo Nishinarita Shinichi Niwano Hiroe Niwano Hironori Nakamura Daiki Saito Tetsuro Sato Gen Matsuura Yuki Arakawa Shuhei Kobayashi Yuki Shirakawa Ai Horiguchi Naruya Ishizue Tazuru Igarashi Tomoharu Yoshizawa Jun Oikawa Yoshinobu Hara Takafumi Katsumura Jun Kishihara Akira Satoh Hidehira Fukaya Hiroyuki Sakagami Junya Ako Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atrial fibrillation atrial remodeling canagliflozin oxidative stress sodium–glucose cotransporter 2 inhibitor |
| title | Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model |
| title_full | Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model |
| title_fullStr | Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model |
| title_full_unstemmed | Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model |
| title_short | Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model |
| title_sort | canagliflozin suppresses atrial remodeling in a canine atrial fibrillation model |
| topic | atrial fibrillation atrial remodeling canagliflozin oxidative stress sodium–glucose cotransporter 2 inhibitor |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.119.017483 |
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