© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Cardiomyocyte remodelling during myocardial hibernation and atrial fibrillation: prelude to apoptosis
aDepartment of Molecular Cell Biology & Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
bDepartment of Morphology, Life Sciences, Janssen Research Foundation, B-2340 Beerse, Belgium
cDepartment of Cardiovascular Surgery, Catholic University of Leuven, Leuven, Belgium
dDivision of Cardiology, University of Louvain Medical School, Brussels, Belgium
eDepartment of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
* Corresponding author. Tel.: +32-14-602-458; fax: +32-14-605-788
Objective: Similar structural changes in the myocardium can be observed in chronic hibernating myocardium and in myocardium taken from hearts suffering chronic atrial fibrillation. We investigated whether or not these changes are indicative of apoptosis. Methods: Myocardial biopsies from 28 strictly selected patients with chronic hibernating myocardium and heart samples from 13 goats with pacing-induced chronic atrial fibrillation were used. Special attention was paid to processing the tissues immediately (fixation/freezing) in order to prevent artificial degenerative changes, thereby excluding false positive identification of apoptosis. Infarcted areas or infarcted border zones were excluded from our study. Apoptosis was detected with light and electron microscopy and terminal deoxynucleotidyl transferase nick end-labelling. Immunohistochemistry was used for detecting Bcl-2, P53 and PCNA-proteins associated with apoptosis/DNA damage. Results: The results obtained for chronic hibernating left ventricular myocardium were similar to those for chronic fibrillating atrial myocardium. No apoptotic nuclei, as characterised by extensive chromatin clumping, could be observed in normal or dedifferentiated cardiomyocytes under the electron microscope. The end-labelling assay did not reveal any cardiomyocytes with damaged DNA. Nor could we find any evidence of substantial expression of Bcl-2, P53 or PCNA, a result indicative of the absence of apoptotic threat or DNA damage. Conclusion: Cardiomyocyte dedifferentiation, but not extensive degeneration through apoptosis, can be observed in chronic hibernating myocardium and chronic fibrillating atrium. Dedifferentiation may be the best way to survive prolonged exposure to the unfavourable conditions imposed by increased wall stress, a relative lowered oxygen environment, or both.
KEYWORDS Apoptosis; Atrial function; Hibernation; Histopathology; Remodelling
This work was presented in part at the 70th Scientific Sessions of the American Heart Association, Orlando, Florida, USA.
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