A chronic mouse model of myocardial ischemia-reperfusion: Essential in cytokine studies

T. O. Nossuli, V. Lakshminakayanan, G. Baumgarten, George Taffet, C. M. Ballantyne, L. H. Michael, M. L. Entman

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

Reperfusion of the ischemic myocardium is associated with a cytokine cascade that reflects a cellular response to injury. We studied this cascade in the mouse and found that acute surgical trauma in sham-operated animals obscured early changes in cytokine induction that occur during myocardial ischemia-reperfusion (MI/R). Therefore, we utilized a new implantable device that allows occlusion and reperfusion of the left anterior descending coronary artery in a closed-chest mouse at any time after instrumentation. Induction of interleukin (IL)-6 and tumor necrosis factor (TNF)-α mRNA in the whole heart was examined by RNase protection assay and quantitated by Phosphor-Imager. At 3 h after instrumentation, levels of IL-6 mRNA in sham- operated animals increased above those of control naive hearts, whereas this increase did not occur until after 1 day for TNF-α mRNA. The surgical trauma led to exaggeration of I/R cytokine induction with greater variance in response. At 3 days and 1 wk after instrumentation, levels of both IL-6 and TNF-α mRNA in sham-operated animals were comparable to those of naive hearts and induction responses in I/R were much less variant. We also found that 1 h of ischemia and 2 h of reperfusion at all time points of recovery (i.e., 3 h and 1, 3, and 7 days after instrumentation) led to a significant increase in IL-6 and TNF-α mRNA levels. In addition, 3 h of permanent occlusion, which did not induce any mRNA increase after 1 wk postinstrumentation, caused marked upregulation of IL-6 mRNA in an acutely prepared animal. This study of early cytokine responses evoked by MI/R highlights the need for dissipation of acute surgical trauma by using a chronic, closed-chest mouse preparation.

Original languageEnglish (US)
Pages (from-to)H1049-H1055
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume278
Issue number4 47-4
DOIs
StatePublished - Apr 2000

Keywords

  • Cytokine
  • Inflammation
  • Interleukin
  • Murine
  • Surgery

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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