ISSN:
1573-4919
Keywords:
hibernating myocardium
;
repair mechanism
;
functional recovery
;
TGF-β1
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract Recently, we proposed the hypothesis that a vicious cycle exists in human hibernating myocardium (HM) between the progression of myocyte degeneration and the development of fibrosis [1]. We now investigated the pathomechanism of this cycle in more detail and established a correlation between the severity of the morphological changes and the degree of postoperative functional recovery of HM. HM was diagnosed by dobutamine echocardiography, thallium-201 scintigraphy and radionuclide ventriculography. Functional recovery was present at 3 months after coronary bypass surgery but remained unchanged at 15 months. Forty patients were subdivided into 2 groups: A with complete and B with incomplete recovery. Biopsies taken during surgery and studied by electron microscopy, immunocytochemistry, rt-PCR, and morphometry revealed myocyte degeneration and inflammatory and fibrinogenic changes in a widened interstitial space. We report here for the first time an upregulation of TGF-β1 evident by a 5-fold increase of fibroblasts and macrophages exhibiting a TGF-β1 content 3-fold larger than in control, and a 〉 3-fold increase in TGF-β1 mRNA by rt-PCR. The number of angiotensin converting enzyme (ACE) containing structures was increased (n/mm2: control - 11.4, A - 17.6, B - 19.2, control vs. A and B, p 〈 0.05). Fibrosis was more severe in group B than A or control (%: C - 10.1; A - 21.2; B - 40.6; p 〈 0.05). Capillary density was significantly reduced (n/mm2: C - 1152; A - 782; B - 579, p 〈 0.05) and intercapillary distance was widened (μm: C - 29.5, A - 36.1, B - 43.3, p 〈 0.05). The number of CD 3 (n/mm2: C - 5.0; A - 9.6; B - 9.4, ns) and CD 68 positive cells (n/mm2: C - 37.2; A - 80.7; B - 55.0, C vs. A p 〈 0.05) was elevated in HM as compared to control indicating an inflammatory reaction. Cut-off points for functional recovery are fibrosis 〉 32%, capillary density 〈 660/mm2 and intercapillary distance 〉 39.0 μm. In HM a self-perpetuating vicious cycle of tissue alterations leads to progressive replacement fibrosis and continuous intracellular degeneration which should be interrupted by early revascularization.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007182617215
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