Combined effects of up- and downstream therapies on atrial fibrillation in a canine rapid stimulation model
| Autor: | Masahiko Moriguchi, Michiro Kiryu, Hidehira Fukaya, Daisuke Sato, Shinichi Niwano, Shoji Hirasawa, Tohru Izumi, Hiroe Niwano, Yoshihiko Masaki |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Combination therapy Bepridil Hemodynamics Down-Regulation Tetrazoles Stimulation Nerve conduction velocity Dogs Heart Conduction System Internal medicine Atrial Fibrillation Medicine Animals business.industry Imidazoles Atrial fibrillation Histology medicine.disease Up-Regulation Disease Models Animal cardiovascular system Cardiology Drug Therapy Combination Cardiology and Cardiovascular Medicine business Olmesartan Angiotensin II Type 1 Receptor Blockers Anti-Arrhythmia Agents medicine.drug |
| Zdroj: | International journal of cardiology. 157(2) |
| ISSN: | 1874-1754 |
| Popis: | Background Recent reports suggest angiotensin receptor blockers (ARBs) and some antiarrhythmic agents affect atrial remodeling in atrial fibrillation (AF). We evaluated the effect of combination therapy with olmesartan (Olm) and bepridil (Bep) in a canine model of AF. Methods and results An atrial stimulation device was implanted in 10 dogs undergoing 6-week pacing at 400bpm. They were divided into Olm (2mg/kg/day) (n=5) and Olm+Bep (Olm, 2mg/kg/day; Bep, 10mg/kg/day) groups (n=5). Atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility were evaluated weekly, and hemodynamics, atrial histology, and mRNA expression and protein expression of ion-channel and gap junction-related molecules at 6weeks. Data were compared between groups and with non-pacing control and pacing-control groups from our previous report. The pacing-control group exhibited shortened AERP, decreased CV, increased AF inducibility and tissue fibrosis, and down-regulated L-type Ca 2+ channel (LCC), SCN5A, Kv4.3 and connexin43 (Cx43). By comparison, the Olm group exhibited suppression of the decrease in CV and of the increase in AF inducibility, but no change in AERP shortening. The Olm+Bep group exhibited suppression of AERP shortening as well as the greatest decrease in AF inducibility. Histologically, tissue fibrosis was suppressed in Olm and Olm+Bep groups. Down-regulation of Cx43 was partly suppressed in the Olm group while that of LCC, SCN5A, and Cx43 was suppressed in the Olm+Bep group. Conclusion Olm and Bep in combination suppressed AF inducibility more strongly than Olm alone, and may be more useful in the suppression of AF. |
| Databáze: | OpenAIRE |
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