Progression of heart failure: A role for interstitial fibrosis
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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<0.03). 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 μm) (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.
Key wordsheart failure ventricular function interstitial fibrosis coronary microcirculation
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- 1.Ertl G, Kochsiek K: Development, early treatment, and prevention of heart failure. Circulation 87: IV-1–IV-2, 1993Google Scholar
- 3.Konstam MA, Rousseau MF, Kronenberg MW, Udelson JE, Melin J, Stewart D, Dolan N, Edens TR, Ahn S, Kinan D, Howe DM, Kilcoyne L, Metherall J, Benedict C, Yusuf S, Pouleur H: Effects of the angiotensin converting enzyme inhibitor enalapril on long-term progression of left ventricular dysfunction in patients with heart failure. Circulation 86: 431–438, 1991Google Scholar
- 8.Sharov VG, Sabbah HN, Shimoyama H, Ali AS, Levine TB, Lesch M, Goldstein S: Abnormalites of contractile structures in viable myocytes of the failing heart. Intl J Cardiol 43: 287–297, 1994Google Scholar
- 10.Schaper J, Hein S: The structural correlate of reduced cardiac function in human dilated cardiomyopathy. Heart Failure 9: 95–111, 1993Google Scholar
- 12.Grossman W: Clinical measurements of vascular resistance and assessment of vasodilator drugs. In: W. Grossman and D.S. Baim (eds). Cardiac Catheterization, Angiography and Intervention. Lea and Febiger, Philadelphia, 1991, pp 143–151Google Scholar
- 16.Rakusan K: Oxygen in Heart Muscle. Charles C. Thomas, Springfield, 1971, pp 22–33, 66–71Google Scholar
- 17.Dzau VJ: Circulating versus local renin-angiotensin system in cardiovascular homeostasis. Circulation 77: I-4–I-13, 1988Google Scholar
- 22.Meerson FZ: The myocardium in hyperfunction, hypertrophy and heart failure. Circ Res 25: 1–163, 1963Google Scholar
- 25.Shimoyama H, Sabbah HN, Sharov VG, Cook J, Lesch M, Goldstein S: Accumulation of interstitial collagen in the failing left ventricular myocardium is associated with increased anaerobic metabolism among affected cardiomyocytes (Abstr). J Am Coll Cardiol, Special Issue: 98A, 1994Google Scholar
- 26.Sharov VG, Sabbah HN, Kono T, Ali AS, Shimoyama H, Lesch M, Goldstein S: Ultrastructural abnormalities of cardiomyocytes in the border zone of old infarctions: studies in dogs with chronic heart failure (Abstr). FASEB J 7: A112, 1993Google Scholar