難治性心不全におけるOP-41483・α-CD，Prostacyclin analog，の効果—血管拡張薬としての有用性

Effects of OP-41483･α-CD, a prostacyclin analog, in the treatment of congestive refractory heart failure: Efficacy as a vasodilator

　虚血性心疾患をはじめ各種心疾患におけるprostaglandin代謝の重要性が指摘され，prostacyclin（PGI₂）やthromboxane A₂（TXA₂）らの血管作動性prostanoidsを調節することにより，臨床面に役立てようとの試みがなされつつある。

　特にPGI₂は冠血管拡張作用，血小板凝集抑制作用に加え全身血管の拡張作用を有することから^1〜3）虚血性心疾患における抗狭心作用^4,5），さらにうっ血性心不全治療における血管拡張薬としての有用性が報告されている^6,7）。しかし，PGI₂には投与法や生物学的安定性に問題があるため，それ自体の臨床応用は困難であった。

　To assess acute hemodynamic effects of OP-41483･α-CD (OP), a stable prostacyclin analog, in patients with congestive heart failure (CHF), OP was administered in 10 patients with CHF resistant to conventional therapy (six with dilated cardiomyopathy and four with myocardial infarction). Hemodynamic changes were evaluated before and at 30 min after OP administration.

　OP (20ng/kg/min) caused an increase in cardiac index (1.91±0.10 to 2.54±0.10 liters/min/ M², p< 0.01), stroke volume index (22.4±2.3 to 30.9±2.3ml/M², p< 0.01) and stroke work index (18.9±2.4 to 25.9±2.4g･m/M², p< 0.01) and a decrease in pulmonary arterial diastolic pressure (24.1±2.1 to 18.3±1.3mmHg, p< 0.01) and mean right atrial pressure (7.6±1.0 to 4.2±1.0 mmHg, p< 0.05). Mean arterial pressure (86.7± 4.2 to 81.1±4.3mmHg, p< 0.01) and double product (10.3±1.1 to 9.3±0.9×10³mmHg･beats/ min, p< 0.05) decreased with no change in heart rate. Both systemic and pulmonary vascular resistance also decreased from 2270±113 to 1604±56 dynes･sec/cm⁵ (p< 0.01) , and from 240±47 to 147±19 dynes･sec/cm⁵ (p< 0.05) respectively.

　Seven of ten patients became flushed, but no patients experienced severe adverse side effects that necessitated to stop the infusion.

　These results suggested that OP is a potent vasodilator with both arterial and venous effects and the clinical use of OP is effective and safe in the treatment of CHF.