Effects of a sustained-release form of isosorbide dinitrate on left atrial pressure in dogs with experimentally induced mitral valve regurgitation.

Abstract

BACKGROUND: The effects of isosorbide dinitrate (ISDN) have not been sufficiently investigated in conscious dogs with mitral valve regurgitation (MR). OBJECTIVE: The objective was to investigate the effects of a sustained-release form of ISDN (sr-ISDN) on hemodynamics and the autonomic nervous system in dogs with MR. ANIMALS: Six healthy Beagles weighing 11.2 &#xb1; 2.2 kg (2 years of age; 2 males and 4 females) were used. METHODS: Experimental, crossover, and interventional study. Dogs with experimentally induced MR were administered placebo, 2, 5, and 10 mg/kg sr-ISDN PO on separate days with a 7-day washout period between randomized dosings. Left atrial pressure (LAP) had been recorded continuously from 30 minutes before administration of sr-ISDN to 12 hours after administration. RESULTS: LAP was significantly decreased after administration in the 5 and 10 mg/kg groups. Significant decrease was observed at 3 and 4 hours after administration in the 5 mg/kg group. In the 10 mg/kg group, significant decrease was observed at 2, 3, 4, 5, 6, 7, 10, and 11 hours after administration. The lowest value was observed at 4 hours after administration in the 5 and 10 mg/kg groups (20.9 &#xb1; 4.2 to 15.9 &#xb1; 3.9 mmHg, P < .01, and 21.3 &#xb1; 4.0 to 13.6 &#xb1; 4.2 mmHg, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Sustained-release form of ISDN showed significant decrease of LAP in the 5 mg/kg and 10 mg/kg groups, and duration of effect was dose related.