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


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]


CONCLUSIONS
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.
Abbate
Antonio
A
Department of Medicine, Virginia Commonwealth University MCV Campus, Richmond, VA, USA. abbatea@yahoo.com
Bussani
Rossana
R
Biondi-Zoccai
Giuseppe G L
GG
Santini
Daniele
D
Petrolini
Alessandro
A
De Giorgio
Fabio
F
Vasaturo
Fortunata
F
Scarpa
Susanna
S
Severino
Anna
A
Liuzzo
Giovanna
G
Leone
Antonio Maria
AM
Baldi
Feliciano
F
Sinagra
Gianfranco
G
Silvestri
Furio
F
Vetrovec
George W
GW
Crea
Filippo
F
Biasucci
Luigi M
LM
Baldi
Alfonso
A
D000199:Actins / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D001344:Autopsy; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D023921:Coronary Stenosis / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D020257:Ventricular Remodeling / Q000502:physiology*
D000199:Actins; D015415:Biomarkers; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases