Cardiomyocyte remodelling during myocardial hibernation and atrial fibrillation: prelude to apoptosis

Objective: Similar structural changes in the myocardium can be observed in chronic hibernating myocardium and in myocardium taken from hearts sufferin g 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 fr om 13 goats with pacing-induced chronic atrial fibrillation were used. Spec ial attention was paid to processing the tissues immediately (fixation/free zing) in order to prevent artificial degenerative changes, thereby excludin g false positive identification of apoptosis. Infarcted areas or infarcted border zones were excluded from our study. Apoptosis was detected with ligh t and electron microscopy and terminal deoxynucleotidyl transferase nick en d-labelling. Immunohistochemistry was used for detecting Bcl-2, P53 and PCN A-proteins associated with apoptosis/DNA damage. Results: The results obtai ned for chronic hibernating left ventricular myocardium were similar to tho se for chronic fibrillating atrial myocardium. No apoptotic nuclei, as char acterised by extensive chromatin clumping, could be observed in normal or d edifferentiated cardiomyocytes under the electron microscope. The end-label ling 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 resul t indicative of the absence of apoptotic threat or DNA damage. Conclusion: Cardiomyocyte dedifferentiation, but not extensive degeneration through apo ptosis, can be observed in chronic hibernating myocardium and chronic fibri llating 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. (C) 1999 Elsevier Science B. V. All rights reserved.