Hirohisa Yamashita

Effect of xamoterol in Shy-Drager syndrome.

BackgroundXamoterol, a cardioselective β1-adrenoceptor partial agonist, has been reported to be effective on postural hypotension. We investigated the effect of xamoterol in five patients with Shy-Drager syndrome (SDS) in relation to their prevailing sympathetic nerve activity and sensitivity of β-adrenoceptors and the change in circadian variation of blood pressure. Methods and ResultsAmbulatory blood pressure over 24 hours was monitored by noninvasive sphygmomanometer (model 5200, Spacelab). Plasma norepinephrine levels of SDS patients were significantly lower than that of normal subjects (n=5) both at rest (54±15 versus 178±83 pg/ml) and after 10-minute standing (74±24 versus 318±143 pg/ml). Infusion of isoproterenol (0.02 μg/kg/min) produced a mild rise of systolic blood pressure and tachycardia in normal subjects but resulted in marked hypotension and tachycardia in SDS subjects. After xamoterol administration (200 mg b.i.d.), systolic blood pressure and heart rate were significantly increased in the averages during the day; however, increases were more pronounced at night. In two of the five patients, the improvement in dizziness was large enough to enable them to increase their daily activities. ConclusionsOur observations suggest that 1) β1-selective, high intrinsic sympathomimetic activity of xamoterol increases blood pressure and heart rate in patients with SDS as a consequence of their prevailing β1-adrenoceptor hypersensitive state, and 2) blood pressure monitoring over 24 hours appears to have important advantages in evaluating the therapeutic effects on postural hypotension.

Transient pulsus alternans induced by isosorbide dinitrate: echocardiographic and hemodynamic evidence of reduced venous return--a case report.

Transient pulsus alternans was induced by isosorbide dinitrate (ISDN) in a patient with postmyocarditis congestive heart failure under diuretic therapy. The severity and duration of pulsus alternans depended on the dose of ISDN. According to the echocardiographic and hemodynamic examinations, the superimposed preload reduction caused by ISDN combined with decreased blood volume owing to diuretic therapy most likely contributed to the development of pulsus alternans.

Effects of a β-agonist and antagonist on the pulmonary circulation and the pulmonary pressor response to 5-HT

We investigated the effects of beta-agonist and antagonist (isoproterenol, propranolol) on the pulmonary circulation and on the pulmonary pressor response to 5-HT in an isolated canine lung lobe. The pulmonary vessels were dilated by isoproterenol at doses up to 200 micrograms, but were constricted by alpha-adrenoceptor stimulation at relatively high doses. The mechanism by which isoproterenol inhibited the 5-HT response is probably related to the stimulation of beta-adrenoceptors at the lower doses and to the stimulation of alpha-adrenoceptors at the higher doses. Propranolol alone had no effect on pulmonary vascular tone, but inhibited the 5-HT response markedly at doses high, possibly by directly blocking the 5-HT receptors.

Pindolol inhibits the development of hypoxic pulmonary vasoconstriction

We examined the effects of beta-adrenoceptor antagonists, propranolol and pindolol, on hypoxic pulmonary vasoconstriction using isolated, blood-perfused dog lung lobes. Pindolol markedly inhibited the development of hypoxic pulmonary vasoconstriction, whereas propranolol had no effect. The different role of the drugs on hypoxic pulmonary vasoconstriction is discussed.

A CASE OF PULMONARY ALVEOLAR PROTEINOSIS

症例は, 47才,男性,教員.主訴は,労作時息切れ,咳嗽,喀痰. 28才頃より慢性気管支炎と言われていたが,最近息切れが増強し受診した.理学的所見では,胸部で両下肺野後面に少数の捻髪音が聴かれ,軽度のばち状指趾が認められた.胸部写真では,左右両下肺野に淡い微細粒状影を,呼吸機能検査では,拘束性障害と拡散能力の低下を,動脈血ガス分析では,低酸素血症と過換気の状態を認めた.開胸肺生検により組織学的に肺胞蛋白症と診断された. L-シスチン内服で若干の改善が認められたが, Ramirez-Rらの方法に準じて病変の高度な左肺の肺洗浄を施行し,自覚的および他覚的症状は著明に改善された.肺洗浄液の分析では,蛋白と燐脂質は正常であり,燐脂質ではレシチンとスフィンゴミエリンが主であつた.レシチン画分では,パルミチン酸が高値を示し,洗浄液脂質の主成分はlung surfactantと近似していた.肺胞蛋白症は,血清とII型肺胞上皮細胞に由来する物質が,何らかの原因により肺胞クリアランス機構が障害されるため肺胞内に異常に蓄積し,さらに悪循環を形成するために生ずると考えられる.従来は死亡率がかなり高いとされたが,肺洗浄などの積極的な治療で著明な改善を期待できる疾患であるので,早期発見および治療が重要である.疑わしい症例に対しては,積極的に喀痰の分析,肺生検などの確診の得られる検査を行なう必要がある.