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. 2000 Apr;278(4):H1049-55.
doi: 10.1152/ajpheart.2000.278.4.H1049.

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

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

T O Nossuli et al. Am J Physiol Heart Circ Physiol. 2000 Apr.
Free article

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)-alpha 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-alpha 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-alpha 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-alpha 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.

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  • For want of a few good shams.
    Entman ML, Nossuli TO, Lakshminarayanan V, Michael LH. Entman ML, et al. Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1017-8. doi: 10.1152/ajpheart.2000.278.4.H1017. Am J Physiol Heart Circ Physiol. 2000. PMID: 10749692 No abstract available.

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