重症心不全に対するPrazosinによる血管拡張剤療法—1回投与時の血行力学的変化と継続投与の検討について

Vasodilator therapy with prazosin for severe congestive heart failure:hemodynamic effects of oral single administration and chronic use

　近年，心不全に対する伝統的な治療法でもある強心剤・利尿剤に加え，血管拡張剤が新しく第3の治療法として注目され始めた^1〜6）。心筋梗塞^7〜9），逆流性弁膜症（大動脈弁閉鎖不全症，僧帽弁閉鎖不全症）^1,10），うっ血型心筋症^11,12）など種々の原因による心不全に対し，Nitro—prusside^7）10），Phentolamine^9），Nitroglycerin^13）などが経静脈的に投与され，また長期使用では，Nitroglycerin^8），Isosorbide dinitrate^14,15），　Hydralazine^10,16,17）などが舌下，経口，あるいは軟膏として経皮的に投与を試みられている。経口剤としてよく用いられている薬剤の中でIsosorbide dinitrate等亜硝酸塩は主として静脈系に対して作用するため静脈還流を減らし，上昇した肺動脈圧を下げることにより肺うっ血の改善には有効であるが，低下している心拍出量にはほとんど影響を与えない。逆にHydralazineは主に動脈系に作用するため，後負荷を軽減することにより，低下している心拍出量の改善には有効であるが，肺うっ血に対する効果は弱い。

The hemodynamic effects of a long-acting vasodilator prazosin were studied in 11 patients with severe congestive heart failure, which be-came refractory to conventional therapy with digitalis and diuretics. In 7 patients with con-gestive cardiomyopathy or regurgitant valvular heart diseases, mean pulmonary artery pressure began to decrease after one hour of oral admin-istration of 2mg prazosin and cardiac index to increase after 2 hours. These hemodynamic effects reached at peak value after 3 and 5 hours of administration respectively and lasted after 6 hours or more. In other 5 patients with mitral stenosis, primary pulmonary hepertension or ven-tricular septal defect with aortic regurgitation, there were no beneficial hemodynamic changes.

In 8 patients prazosin was administrated for long period (2~8 mg/day, 18 days~9 months). Seven of them were the above-mentioned patients, who had beneficial hemodynamic effects for a single administration, and another of them was a patient with congestive cardiomyopathy who was not given any hemodynamic examinations. In 7 of them exertional dyspnea was improved and edema of extremities was disappeared. In 2 patients of the seven, however, congestive symptoms, such as edema, hepatomegaly, pulmo-nary congestion, decrease of urinary output and weight gain, was manifested between the period of 10 to 18 days after administration. These symptoms were hardly treated with diuretics but were im-proved rapidly after stop of administration of prazosin. In conclusion, prazosin was effective to refractory congestive heart failure, but after administration of it clinical symptoms and signs should be carefully checked. If clinical signs of congestive heart failure were deteriorated, prazosin should be stopped immediately.