Histological remodeling in an ovine heart failure model resembles human ischemic cardiomyopathy

Staged coronary embolization, causing myocardial microinfarctions, has been shown in dogs and sheep to cause chronic ischemic heart failure (HF) that resembles the hemodynamics of the human condition. However, its histopathol ogical basis remains unclear. We examined the hypothesis that the ventricul ar remodeling seen in such sheep resembles the histopathology of human isch emic cardiomyopathy (ICM). Understanding the pathophysiology of this model will determine its place in the development of treatment strategies for HF. Global left ventricular (LV) damage resulting in HF was induced by staged coronary embolization in 11 sheep. Six others served as controls (normal co ntrol, NC). In HF sheep, the heart was harvested 6 months after LV ejection fraction (EF) had stabilized at < 35%. Histopathological profiles were com pared in biventricular transverse sections at midpapillary level using comp uted image analysis. LV end-diastolic volume increased in the HF group from 84.9 +/- 29 to 122.4 +/- 30.3 ml (n = 11, P < .05), but myocytes across th e LV wall in noninfarcted zones decreased (435.7 +/- 38.2 NC; 297.8 +/- 48. 4/unit area HF; n = 11, P < .0001) as did myocyte nuclear density (990.5 +/ - 51.5 NC; 677.5 +/- 12 1.1/mm(2) HF, n = 11, P < .0001). In contrast, LV r eplacement and interstitial fibrosis increased as did myocyte diameter in n oninfarcted zones: 0.1 +/- 0.1 to 6.2 +/- 4.5% (P =.0049); 2.0 +/- 1.0 to 7 .6 +/- 3.9% (P=.0149); and 10.0 +/- 0.5 to 15.9 +/- 2.2 mum (P < .0001), re spectively. Although LV myocyte nuclear length increased (10.2 +/- 1.0 NC; 12.2 +/- 0.9 mum HF, n = 11, P=.0006), right ventricular (RV) myocyte nucle ar density and length did not alter. In this ovine chronic HF model, LV dil ation and interstitial and myocyte remodeling resemble human ICM. (C) 2001 Elsevier Science Inc. All rights reserved.