Effects of high-dose alacepril on left atrial pressure and central aortic pressure in awake dogs with mitral valve regurgitation

The purpose of this study was to clarify how alacepril in amounts greater than those recommended on the product labeling approved by drug regulatory agencies affects left atrial pressure (LAP) and central aortic pressure in dogs with experimentally induced mitral valve regurgitation (MR). Six healthy Beagle dogs were surgically induced for MR and received alacepril at either 1.5 mg/kg/12-h (3.0 mg/kg/day) or 3.0 mg/kg/12-h (6.0 mg/kg/day) per one administration for seven days. After a four-week washout period, another dosage was administrated as a crossover study. Dogs were randomised to receive 3.0 mg/kg/day or 6.0 mg/kg/day first. LAP and central systolic (SAP), mean (MAP), and diastolic (DAP) aortic pressure were measured for 24-h before and during the administration of alacepril. The earliest decreases in SAP, MAP, and DAP with 6.0 mg/kg/day were observed on days 4, 4, and 5, respectively. With 3.0 mg/kg/day, the earliest decrease in DAP was observed on day 7. The maximum LAP was decreased on days 5 and 7 with 6.0 mg/kg/day. The mean LAP was decreased on day 7 with 6.0 mg/kg/day. In conclusion, the administration of alacepril at 6.0 mg/kg/day reduced the LAP and central aortic pressure within several days.