Effects of S-596, a new beta-adrenoceptor blocking agent on the left ventricular performance of normal subjects during exercise.

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• The effects of d1-2-(3'-t-butylamino-2'-hydroxypropylthio)4-(5'-carbamoyl-2'-thienyl) thiazole hydrochloride (S-596) were evaluated in 9 normal volunteers. Exercise echocardiography was performed in the semi-supine position before and 2, 4 and 24 hours after the oral administration of 15mg of S-596. Two hours after administration, resting heart rate was unchanged, compared with control, but systolic blood pressure at rest was slightly decreased (114±6 vs 106±10mmHg, p<0.05). Left ventricular dimensions were unchanged, but shortening fraction was increased in the resting state (30.3±4.6 vs 33.1±4.8%, p<0.05). During exercise on oral S-596, heart rate and systolic blood pressure responses were reduced (127±11 in control vs 108±6 beats/min on S-596, 198±25 vs 168±23mmHg, p<0.001 and 0.05, respectively). Left ventricular enddiastolic dimension was not significantly altered by S-596 compared with the preceding control exercise test; however, end-systolic dimension was significantly larger after beta blockade with S-596 (2.6±0.4 vs 3.0±0.4 cm, p<0.05). Shortening fraction and cardiac output decreased significantly (43.7±3.7 vs 40.0±5.7%, 9.5±1.4 vs 8.4±1.3L/min, p<0.05 and 0.01, respectively). These effects of S-596 were maximal at 2 hours after oral administration with reduced response of heart rate to exercise lasting for 24 hours. Compared with the effects of propranolol (30mg, given orally) in the same subjects, beta-adrenergic blockade during exercise with S596 was equivalent to or greater than that of propranolol.Thus, S-596 has little, if any, effect on resting left ventricular performance, but demonstrates potent negative chronotropic and inotropic effects during exercise in normal human subjects. Its beta-adrenergic blocking action also has long acting properties, especially its chronotropic effect.

• International Heart Journal刊行会の論文

著者

• Sugihara Hiroki

  Second Department Of Internal Medicine Kyoto Prefectural University Of Medicine

• FURUKAWA KEIZO

  Second Department of Internal Medicine, Kyoto Prefectural University of Medicine

• Ijichi Hamao

  Second Department Of Internal Medicine Kyoto Prefectural University Of Medicine

• NIKI Shunpei

  Second Department of Medicine, Kyoto Prefectural University of Medicine

• NISHIDA Kazuo

  Second Department of Medicine, Kyoto Prefectural University of Medicine

• YAMADA Chihiro

  Second Department of Medicine, Kyoto Prefectural University of Medicine

• KATSUME Hiroshi

  Second Department of Internal Medicine, Kyoto Prefectural University of Medicine

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