Sonoki H, Uchida Y, Tomaru T, Sugimoto T
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Nihon Yakurigaku Zasshi. 1988 Aug;92(2):119-26. doi: 10.1254/fpj.92.119.
Effects of prazosin, dobutamine, isoproterenol and SGB-1534, a new alpha-blockade, on congestive heart failure (CHF) in dogs were investigated. The model was made by protease injection into the left ventricular free wall, saline loading, and dextran and methoxamine infusions. By this maneuver, left atrial pressure (LAP), systemic vascular resistance (SVR) and left ventricular end-diastolic pressure (LVEDP) were markedly increased, aortic blood flow (AoBF) was decreased, and systemic blood pressure was unchanged. In this model, the intravenous administration of prazosin (0.1 approximately 10.0 micrograms/kg, i.v.) increased AoBF and decreased LAP in a dose-dependent manner. The improvement of the CHF by prazosin was considered to result from its vasodilating action. SGB-1534 (0.1 approximately 10.0 micrograms/kg, i.v.) improved the CHF mainly through its vasodilating and positive inotropic actions, which is because SGB-1534 decreased SVR and increased Vmax. The magnitudes of vasodilation by SGB-1534 was greater than those by prazosin. These data indicate that SGB-1534 is useful in the treatment of CHF. Both dobutamine (5 approximately 100 micrograms/kg, i.v.) and isoproterenol (0.001 approximately 0.1 micrograms/kg, i.v.) improved the CHF through their vasodilating and positive inotropic actions in the canine CHF. The ratio of positive inotropism/vasodilation was greater for dobutamine than isoproterenol. The vasoconstriction by the large dose of dobutamine might participate in this difference between dobutamine and isoproterenol.
研究了哌唑嗪、多巴酚丁胺、异丙肾上腺素以及新型α阻滞剂SGB - 1534对犬充血性心力衰竭(CHF)的影响。通过向左心室游离壁注射蛋白酶、输注生理盐水以及右旋糖酐和甲氧明来制备模型。通过这种操作,左心房压力(LAP)、全身血管阻力(SVR)和左心室舒张末期压力(LVEDP)显著升高,主动脉血流量(AoBF)降低,而全身血压未改变。在该模型中,静脉注射哌唑嗪(0.1至约10.0微克/千克,静脉注射)可使AoBF增加,并使LAP呈剂量依赖性降低。哌唑嗪对CHF的改善被认为是其血管舒张作用的结果。SGB - 1534(0.1至约10.0微克/千克,静脉注射)主要通过其血管舒张和正性肌力作用改善CHF,这是因为SGB - 1534降低了SVR并增加了Vmax。SGB - 1534引起的血管舒张幅度大于哌唑嗪。这些数据表明SGB - 1534可用于治疗CHF。多巴酚丁胺(5至100微克/千克,静脉注射)和异丙肾上腺素(0.001至0.1微克/千克,静脉注射)均通过其血管舒张和正性肌力作用改善犬CHF。多巴酚丁胺的正性肌力作用与血管舒张作用的比值大于异丙肾上腺素。大剂量多巴酚丁胺引起的血管收缩可能参与了多巴酚丁胺与异丙肾上腺素之间的这种差异。