Molecular evidence for induction of intracellular adhesion molecule-1 in the viable border zone associated with ischemia-reperfusion injury of the dog heart.
BACKGROUND
Acute inflammation may play a role in injury during reperfusion following myocardial ischemia. Studies in vitro suggest that intracellular adhesion molecule-1 (ICAM-1) mediates neutrophil adherence to cardiac myocytes and neutrophil-mediated injury. We have shown cytokine activity in postischemic cardiac lymph sufficient to maximally express ICAM-1 on myocytes and that ICAM-1 mRNA is found in the previously ischemic myocardium early in reperfusion.


RESULTS
In the present study, we used in situ hybridization techniques to detect ICAM-1 mRNA and examine the cells of origin, relation to cell injury, and relation to inflammatory infiltration after 1 hour of ischemia and varying times of reperfusion. By 1 hour of reperfusion, ICAM-1 mRNA was detected in much of the ischemic myocardium, except in areas of contraction band necrosis. At 2 and 3 hours, a clear demarcation of necrotic areas surrounding ischemic areas of viable myocardium with ICAM-1 mRNA staining was present, and ICAM-1 mRNA staining increased with time. Nonischemic areas had no visible ICAM-1 mRNA staining in the first 3 hours. By 24 hours of reperfusion, ICAM-1 mRNA was present in both control and ischemic segments (excluding the necrotic areas) compatible with a generalized circulation of cytokines persistent at 24 hours. In the absence of reperfusion, ICAM-1 mRNA staining was not seen in the first 3 hours and was markedly reduced at 24 hours. The interface of viable and necrotic cells also contained the most extensive inflammatory infiltration.


CONCLUSIONS
Evidence is presented that induction of ICAM-1 mRNA has highly specific localization to ischemic but viable myocardium. Induction of ICAM-1 mRNA transcription in early reperfusion may render the viable "border zone" susceptible to neutrophil-induced injury.
Youker
K A
KA
Department of Medicine, Baylor College of Medicine, Houston, TX 77030-3498.
Hawkins
H K
HK
Kukielka
G L
GL
Perrard
J L
JL
Michael
L H
LH
Ballantyne
C M
CM
Smith
C W
CW
Entman
M L
ML
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D004285:Dogs; D005260:Female; D018799:Intercellular Adhesion Molecule-1; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D009205:Myocarditis / Q000209:etiology; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1