PROGRESSION OF HEART-FAILURE - A ROLE FOR INTERSTITIAL FIBROSIS

Progressive deterioration of left ventricular (LV) function is a chara cteristic feature of the heart failure (HF) state. The mechanism or me chanisms responsible for this hemodynamic deterioration are not known but may be related to progressive intrinsic dysfunction, degeneration and loss of viable cardiocytes. In the present study, we tested the hy pothesis that accumulation of collagen in the cardiac interstitium (re active interstitial fibrosis, RIF), known to occur in HF, results in r educed capillary density (CD = capillary/fiber ratio) and increased ox ygen diffusion distance (ODD) which can lead to hypoxia and dysfunctio n of the collagen encircled myocyte. Studies were performed in LV tiss ue obtained from IO dogs with chronic HF (LV ejection fraction 26 +/- 1%) produced by multiple sequential intracoronary microembolizations. In each dog, CD and ODD were evaluated in LV regions that manifested s evere RIF (volume fraction 16 +/- 2%) and in LV regions of little or n o RIF (volume fraction 4 +/- 1%). In regions of severe RIF, CD was sig nificantly decreased compared to regions of no RIF (0.92 +/- 0.02 vs. 1.05 +/- 0.03) (P < 0.003). Similarly, ODD was significantly increased in regions of severe RIF compared to regions of no RIF (15.3 +/- 0.4 vs. 12.2 +/- 0.3 mu m) (P < 0.001). These data suggest that in dogs wi th chronic HF, constituent myocytes of LV regions which manifest sever e RIF may be subjected to chronic hypoxia; a condition that can advers ely impact the function and viability of the collagen encircled cardio cyte.