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European Heart Journal Advance Access originally published online on July 19, 2005
European Heart Journal 2005 26(19):2039-2045; doi:10.1093/eurheartj/ehi419
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Infarct-related artery occlusion, tissue markers of ischaemia, and increased apoptosis in the peri-infarct viable myocardium

Antonio Abbate1,2,*, Rossana Bussani3, Giuseppe G.L. Biondi-Zoccai2,4, Daniele Santini5, Alessandro Petrolini2, Fabio De Giorgio2, Fortunata Vasaturo6, Susanna Scarpa6, Anna Severino2, Giovanna Liuzzo2, Antonio Maria Leone2, Feliciano Baldi7, Gianfranco Sinagra3, Furio Silvestri3, George W. Vetrovec1, Filippo Crea2, Luigi M. Biasucci2 and Alfonso Baldi7

1Department of Medicine, Virginia Commonwealth University MCV Campus, Richmond, VA, USA
2Institute of Cardiology and Department of Forensic Medicine, Catholic University, Rome, Italy
3Institute of Pathological Anatomy and Department of Cardiology, University of Trieste, Trieste, Italy
4Institute of Medical Statistics and Biometrics, University of Milan, Milan, Italy
5Section of Oncology, Campus Bio-Medico University, Rome, Italy
6Department of Experimental Medicine and Pathology, Università ‘La Sapienza’, Rome, Italy
7Department of Biochemistry ‘F. Cedrangolo’, Pathologic Anatomy, Second University of Naples, Naples, Italy

Received 30 November 2004; revised 9 June 2005; accepted 23 June 2005; online publish-ahead-of-print 19 July 2005.

* Corresponding author. Fax: +1 360 3231204. E-mail address: abbatea{at}yahoo.com

Aims Unfavourable cardiac remodelling often complicates acute myocardial infarction (AMI) as a result of increased cardiomyocyte apoptosis. It is currently unclear whether ongoing or recurrent ischaemia is an independent determinant for increased apoptosis in peri-infarct viable myocardium.

Methods and results In order to assess the link between infarct-related artery (IRA) occlusion, ischaemia, and apoptosis, 30 subjects dying 7–120 days after AMI (16 with IRA occlusion and 14 with patent IRA) and five control subjects were selected at autopsy. Cardiomyocytes were defined as apoptotic if co-expressing TUNEL and activated caspase-3. Expression of both hypoxia-inducible factor-1 and cyclo-oxygenase-2 was assessed in the peri-infarct myocardium and considered as tissue markers of ischaemia. Evidence of ischaemia was significantly more frequent in cases with IRA occlusion (53%) than in cases with patent IRA (15%) or control hearts (0%, P=0.026). The finding of IRA occlusion and markers of ischaemia identified cases with higher apoptotic rates (ARs) in the peri-infarct viable myocardium [12.2% (8.2–14.0), P<0.001 vs. others], whereas IRA occlusion without ischaemia was associated with lower AR, not significantly different from patent IRA [3.0% (1.0–7.9) vs. 2.2% (1.0–5.8), respectively, P=0.42]

Conclusion Ischaemia in the peri-infarct viable myocardium is present in over 50% of subjects dying late after AMI with IRA occlusion, and it is associated with increased apoptosis. Relief of ischaemia after AMI may prove of benefit in preventing apoptosis and its consequences.

Key Words: Apoptosis • Ischaemia • Myocardial infarction • Remodelling • Cyclo-oxygenase-2 • Hypoxia-inducible factor-1


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