© 2007 European Society of Cardiology
Relevance of apoptosis in influencing recovery of hibernating myocardium
a Department of Pathological Anatomy, University of Padua Via Gabelli, 61, 35121 Padova, Italy
b Division of Cardiology, University of Padua Italy
c Department of Non-invasive Diagnostic Cardiology, San Raffaele Foundation Institute and University Hospital Milan, Italy
d Department of Cardiac Surgery, San Raffaele Foundation Institute and University Hospital Milan, Italy
e Department of Cardiology, University of Ferrara and Fondazione S. Maugeri IRCSS Gussago, Brescia, Italy
* Corresponding author. Tel.: +39 0 49 8272260; fax: +39 0 49 8272285. E-mail address: annalisa.angelini{at}unipd.it
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Abstract |
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Background: Hibernating myocardium (HM) is viable but dysfunctional myocardium which can recover following revascularization. Myocyte necrosis is virtually absent in HM; however, cellular loss may take place by apoptosis, although this is controversial.
Aim: To assess the presence of apoptosis and its relevance in HM.
Methods: During coronary artery by-pass surgery (CABG), 21 patients underwent transmural biopsy in the dysfunctional left anterior descending artery tributary area of the left ventricle (LV), with kinetic recovery at follow-up, thus fulfilling the HM criteria. All patients underwent echocardiographic follow-up at 12 months. All biopsies were evaluated by light microscopy, electron microscopy (EM), and molecular analysis.
Results: All biopsies were structurally altered, showing increased fibrosis and myocytes with variable size. Myocyte dedifferentiation was not detected by immunohistochemistry or EM. On stepwise linear regression, 1 year LVEF was predicted by the apoptotic index (β=–0.973, p=0.002), the normotrophic cell percentage (β=0.449, p=0.038), and mean fibrosis (β=–0.412, p=0.51).
Conclusions: Our biopsy study detected a wide range of morphological substrate heterogeneity in HM with degenerative features. We have demonstrated for the first time in humans that myocyte apoptosis is an important phenomenon in HM, negatively influencing LV functional recovery after CABG.
Key Words: Hibernating myocardium • Apoptosis • Pathology
Received March 6, 2006; Revised July 28, 2006; Accepted September 19, 2006
1 These authors have equally contributed to this manuscript.