Effect of Sustained Release Isosorbide Dinitrate (EV151) in Dogs with Experimentally-Induced Mitral Insufficiency

Abstract

ABSTRACT. To investigate the hemodynamic effects on seven anesthetized dogs with experimentally-induced mitral insufficiency, isosorbide dinitrate (ISDN) in sustained release form (EV151) was administered at different dosages (0, 2, 8 and 16 mg/kg). The drug administration resulted in altered pulmonary arterial wedge pressure (preload), and cardiac output and total systemic resistance (afterload). Arterial pressure increased in the control group and in animals receiving 2 mg/kg, but decreased in animals 1-2 hr after receivi ng 8 and 16 mg/kg dosages. Cardiac output increased in animals receiving 2, 8 and 16 mg/kg dosages, with concomitant decreases in total systemic resistance. ISDN caused mild vasodilation at 2 mg/kg and severe vasodilation at 8 and 16 mg/kg. Future experiments on nonanesthetized dogs may be of benefit. KEY WORDS: canine, isosorbide dinitrate, mitral insufficiency.

Effects of a Sustained‐Release Form of Isosorbide Dinitrate on Left Atrial Pressure in Dogs with Experimentally Induced Mitral Valve Regurgitation

“…Previous studies reported that ISDN has beneficial acute hemodynamic effects in humans and dogs with MR because of their preload and afterload reducing properties . Nagasawa et al reported that there was a slight decrease in preload and afterload at 2 mg/kg sr‐ISDN . However, in this study, there was no significant change in parameters in the 2 mg/kg group.…”

“…15 Nagasawa et al reported that there was a slight decrease in preload and afterload at 2 mg/kg sr-ISDN. 12 However, in this study, there was no significant change in parameters in the 2 mg/kg group. Compared with the previous study, this study was performed in conscious dogs.…”

“…In this study, duration of effect was dose dependent. According to the previous study, the plasma concentration of isosorbide‐2‐mononitrate (2‐ISMN) and isosorbide‐5‐mononitrate (5‐ISMN), which are metabolites of ISDN, peaked at 4 and 8 hours after ISDN administration, respectively . These peaks of the metabolites were later than the peak of ISDN.…”

“…The sustained‐release form of ISDN (sr‐ISDN) maintains an effective serum concentration for more than 6 hours. Previous study has shown that the effective dose‐response curve for sr‐ISDN in anesthetized dogs with experimentally induced MR appeared to be between 2 and 8 mg/kg . However, no study has been conducted to evaluate the effects of oral administration of sr‐ISDN on LAP in conscious dogs with MR.…”

“…Previous study has shown that the effective dose-response curve for sr-ISDN in anesthetized dogs with experimentally induced MR appeared to be between 2 and 8 mg/kg. 12 However, no study has been conducted to evaluate the effects of oral administration of sr-ISDN on LAP in conscious dogs with MR. In addition, there is no report of the evaluation of the effects of ISDN on the autonomic nervous system.…”