Beneficial effects of MET-88 on left ventricular dysfunction and hypertrophy with volume overload in rats

We examined the effects of MET-88 on haemodynamics and cardiac hypertrophy in rats with an aortocaval shunt (A-V shunt). On the day of surgery, an A-V shunt was produced by using an 18-gauge needle in Wistar rats as described by Garcia and Diebold. MET-88 and captopril were orally administered to ra ts 1 week after surgery, and the administration was continued for 3 weeks. Four weeks after the surgery, A-V shunt-operated rats had biventricular hyp ertrophy and higher right atrial pressure (RAP) and left ventricular end-di astolic pressure (LVEDP) than sham-operated rats. Compared with untreated A -V shunt rats, those treated with MET-88 showed significant attenuation of the development of left ventricular (LV) hypertrophy and of the increased L VEDP. Captopril-treated A-V shunt rats also failed to show increases in LV weight and LVEDP. In in vitro studies, MET-88 had no effect on renin and an giotensin-converting enzyme (ACE) activities in the plasma of normal rats. These results suggest that MET-88 improved LV hypertrophy and LV dysfunctio n in rats with an A-V shunt. Furthermore, the data indicate that the benefi cial effects of MET-88 may be attributed to some pathway, not involving the renin-angiotensin system, such as myocardial energy metabolism, venous ret urn, etc. We conclude that MET-88 may be a novel agent for the therapy of c hronic heart failure. (C) 1999 Editions scientifiques et medicales Elsevier SAS.