1029-18 Early, Long-term Therapy with Enalapril but not Metoprolol or Digoxin Attenuates Cardiocyte Hypertrophy in Dogs with Moderate Heart Failure

Abstract

LV remodeling (enlargement, sphericity and myocyte hypertrophy), is a key process in the progressive deterioration of LV function observed in heart failure (HF). In dogs with moderate HF (LV ejection fraction 30–40%), we previously showed that early, long-term (3 months) monotherapy with enalapril (ENA, 10 mg bid, n = 7) and metoprolol (MET, 25 mg bid, n = 7) but not digoxin (DIG, 0.25 mg qd, n = 7) prevented the progressive LV enlargement observed in untreated dogs (CON, n = 7). In the present study, we used the same cohorts of dogs to examine the effects of these agents on myocyte hypertrophy. Myocyte cross-sectional area (MCSA) was evaluated histologically from frozen LV sections obtained at the end of therapy. From each section, 5 fields (radial orientation). each containing at least 100 myocytes, were selected randomly for analysis using computer-based planimetry. LV tissue from 7 normal (NL) dogs was used for comparison. Average MCSA ( μ m 2 ) NL CON DIG MET ENA 616 ± 18 924 ± 63 922 ± 73 979 ± 41 711 ± 58 * * P < 005 MCSA was larger in CON, MET and DIG dogs compared to NL and ENA dogs (*P < 0.05). No significant difference was present in MCSA between ENA and NL dogs. Only ENA attenuated myocyte hypertrophy in dogs with moderate HF.