부산대학교 도서관

349U85 is a chemically novel, nonglycoside, noncatecholamine cardiotonic-vasodilator agent with a unique cardiovascular profile in vitro and in vivo. 349U85 and milrinone, 10-6to3 x 10-5M each, produce concentration-dependent increases in tension development of 33–60 and 37–60, respectively, with corresponding 5–18 and 17–55 increases in contractile rate, respectively, in guinea pig spontaneously beating isolated paired atria. In anesthetized dogs, 349U85 at 0.03–1.0 mg/kg i.v. produces dose-dependent increases in left ventricular contractility (dPIdt) of 12–159, decreases in total peripheral resistance of 11–38, and increases in heart rate of 3–26. Milrinone, Cl-914, and enoximone produce comparable increases in dP/dtand decreases in peripheral resistance yet increase the heart rate a maximum of 71, 49, and 41, respectively. Intra-arterial injection of 349U85 into the vascularly isolated hindlimb of anesthetized dogs produces dose-dependent direct vasodilation. The inotropic effect of 349U85, following a single intravenous dose, is sustained in excess of 4 h while comparable initial inotropic effects of milrinone and enoximone are sustained less than 1 and 2.5 h, respectively. 349U85 effectively reverses acute cardiac depression in anesthetized dogs with a duration exceeding that of milrinone. In conscious dogs, 349U85, at 0.1–1.0 mg/kg p o., produces a dose-dependent positive inotropic effect (15–73) with no significant effect on heart rate. Following a single oral dose of 349U85, the inotropic effect is sustained in excess of 6 h. Results of these studies indicate that 349U85 is a potent, long-lasting positive inotropic and vasodilator agent with minimal heart rate effect in vitro and in vivo and is different from a number of reference inodilators.