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.