Progression of heart failure: a role for interstitial fibrosis
H N Sabbah1, V G Sharov, M Lesch
1Department of Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan, USA.
Insights
Heart failure (HF) involves worsening left ventricular (LV) function. Collagen buildup in HF reduces capillary density and increases oxygen diffusion distance, potentially causing myocyte hypoxia and dysfunction.
Area of Science:
- Cardiovascular Science
- Cardiac Pathophysiology
- Heart Failure Research
Background:
- Progressive left ventricular (LV) dysfunction characterizes heart failure (HF).
- Mechanisms of hemodynamic deterioration in HF remain unclear, possibly involving cardiocyte loss.
- Reactive interstitial fibrosis (RIF) is a known feature of HF.
Purpose of the Study:
- To test if RIF in HF reduces capillary density (CD) and increases oxygen diffusion distance (ODD).
- To investigate if RIF-induced changes lead to myocyte hypoxia and dysfunction.
- To evaluate the relationship between RIF, CD, and ODD in chronic canine HF.
Main Methods:
- Studied LV tissue from 10 dogs with chronic HF (ejection fraction 26 ± 1%).
- HF was induced by sequential intracoronary microembolizations.
- Assessed CD (capillary/fiber ratio) and ODD in regions with severe RIF vs. minimal RIF.
Main Results:
- Severe RIF regions showed significantly decreased capillary density (0.92 ± 0.02 vs. 1.05 ± 0.03).
- Severe RIF regions exhibited significantly increased oxygen diffusion distance (15.3 ± 0.4 vs. 12.2 ± 0.3 microns).
- These changes were statistically significant (P < 0.003 for CD, P < 0.001 for ODD).
Conclusions:
- In chronic canine HF, severe RIF is associated with reduced capillary density and increased oxygen diffusion distance.
- These RIF-induced microvascular changes suggest myocytes in fibrotic regions may experience chronic hypoxia.
- Hypoxia in collagen-encircled myocytes could adversely affect their function and viability in heart failure.
Abstract:
Progressive deterioration of left ventricular (LV) function is a characteristic feature of the heart failure (HF) state. The mechanism or mechanisms 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 hypothesis that accumulation of collagen in the cardiac interstitium (reactive interstitial fibrosis, RIF), known to occur in HF, results in reduced capillary density (CD = capillary/fiber ratio) and increased oxygen diffusion distance (ODD) which can lead to hypoxia and dysfunction of the collagen encircled myocyte. Studies were performed in LV tissue obtained from 10 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 severe RIF (volume fraction 16 +/- 2%) and in LV regions of little or no RIF (volume fraction 4 +/- 1%). In regions of severe RIF, CD was significantly 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 microns) (P < 0.001). These data suggest that in dogs with chronic HF, constituent myocytes of LV regions which manifest severe RIF may be subjected to chronic hypoxia; a condition that can adversely impact the function and viability of the collagen encircled cardiocyte.
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