Molecular evidence for induction of intracellular adhesion molecule-1 in the viable border zone associated with ischemia-reperfusion injury of the dog heart

Keith A. Youker, Hal K. Hawkins, Gilbert L. Kukielka, Jerry L. Perrard, Lloyd H. Michael, Christie M. Ballantyne, C. Wayne Smith, Mark L. Entman

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)2736-2746
Number of pages11
JournalCirculation
Volume89
Issue number6
DOIs
StatePublished - Jun 1994

Keywords

  • genetics
  • hybridization
  • leukocytes
  • myocardium
  • reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Youker, K. A., Hawkins, H. K., Kukielka, G. L., Perrard, J. L., Michael, L. H., Ballantyne, C. M., Smith, C. W., & Entman, M. L. (1994). Molecular evidence for induction of intracellular adhesion molecule-1 in the viable border zone associated with ischemia-reperfusion injury of the dog heart. Circulation, 89(6), 2736-2746. https://doi.org/10.1161/01.CIR.89.6.2736