β1 partial agonist（Xamoterol）の変時作用および不整脈誘起性に関する臨床的検討

Assessment of chronotropic effect and arrhythrnogenesis on β1-partial agonist (Xamoterol) in chronic heart failure

　近年，ジギタリスに代わる新たな強心薬が次々と開発^1〜3）され，臨床試用されるようになってきた。機序は種種であるが，その一つに経口投与できるβ刺激薬^4〜5）があり，優れた強心効果がすでに報告されている。しかし，β刺激薬はドパミン，ドブタミン，イソプロテレノールなどで知られているように陽性変力作用のみでなく陽性変時作用と不整脈誘起作用を持つ。経口β刺激薬ではこの二つの作用の兼ね合いが臨床応用できるか否かの鍵になるといえる。強心薬Xamoterolはβ₁ partial agonistとして新しく開発され，receptorに対する強いaffinityと比較的弱い刺激作用を持つβ刺激薬である。本研究では強心作用が得られる200〜400mgのXamoterolを投与し^6）変時作用，不整脈誘起作用について検討した。

Xamoterol is a newly synthesized β₁ -partial agonist. Recent reports showed its inotropic effect in patients with heart failure. The purpose of this study is to assess its chronotropic effect and arrhythmogenesis. Holter electrocardiography was used for evaluation of arrhythmia and heart rate in 27 patients (18 with normal sinus rhythm (NSR), 8 with atrial fibrillation (Af) and 1 with atrial flutter) with chronic heart failure. Two hundred mg and 400 mg of Xamoterol was given orally twice daily for 2 to 30 months. Clinical symptoms of heart failure were improved in 17 of 27 patients. There were no sudden death and no syncope observed. The minimum, maximum and mean hourly heart rate between 22 : 00 and 06 : 00 hour during treatment were significantly higher than control period (p< 0.05). While, the maximum heart rate between 07 : 00 and 21 : 00 hour was lower (p <0.05-0.01) in patients with both NSR and Af. Total number of VPC during the treatment was not increased except for 3 patients. Neither de novo atrial fibrillation nor new PSVT was observed. There were 9, 12 and 3 patients with ventricular tachycardia before, 200 mg and 400 mg treatment period, respectively. No sustained VT was found.

Conclusion : ( 1 ) Clinical symptoms in patients with chronic heart failure were improved with oral treatment with Xamoterol. ( 2 ) Xamoterol has a dual action on heart rate, that is, stabilizing action of heart rate. ( 3 ) No arrhythmogenic effect of Xamoterol was observed.