Cardiohemodynamic effects of MS-857 in pacing induced heart failure

• Published in: Japanese Journal of Pharmacology Vol. 64; no. suppl.1; p. 266
• Main Authors: Hori, Katsuhiko, Suga, Hiroyuki, Maruyama, Masahiko, Kamiya, Joji
• Format: Journal Article
• Language: Japanese; English
• Published: The Japanese Pharmacological Society 1994
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)50698-9

Beneficial effects of MS-857, an orally active phosphodiesterase III inhibitor, have been demonstrated on the failing heart in several canine acute heart failure models. In the present study, we studied the effects of MS-857 on cardiac contractility and hemodynamics in a conscious canine pacing induced chronic heart failure model. Following continuous rapid ventricular pacing at 260 beats/min for 3 weeks, severe heart failure was induced; left ventricular (LV) dP/dt_max was significantly decreased and, heart rate and end-diastolic pressure were significantly increased. MS-857 (3-300μg/kg) was intravenously administered before and after ventricular pacing. In the control state, MS-857 caused significant increases in LVdP/dt_max and heart rate in a dose-dependent manner with no effect on blood pressure. In the heart failure state, MS-857 dose-dependently increased LVdP/dt_max as potently as in the control state. On the other hand, MS-857 caused a slight decrease in heart rate in higher doses used. To assess the effect of MS-857 on cardiac function, a ventricular function curve was obtained by interruption of venous return with caval occlusion. Intravenous infusion of MS-857 (3μg/kg/min) reversed the depressed ventricular function in the heart failure state. These results suggest that MS-857 has a beneficial effect in the treatment of congestive heart failure.