The Journal of Thoracic and Cardiovascular Surgery
Volume 128, Issue 4 , Pages 588-594 , October 2004

FR167653 diminishes infarct size in a murine model of myocardial ischemia-reperfusion injury

  • Masaki Yada, MD

      Affiliations

    • Department of Thoracic & Cardiovascular Surgery, Mie University School of Medicine, Tsu, Japan
    • ,
  • Akira Shimamoto, MD, PhD

      Affiliations

    • Department of Thoracic & Cardiovascular Surgery, Mie University School of Medicine, Tsu, Japan
    • Division of Cardiothoracic Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Wash, USA
    • Corresponding Author InformationAddress for reprints: Akira Shimamoto, MD, PhD, Division of Cardiothoracic Surgery, Department of Surgery, University of Washington School of Medicine, 1959 NE Pacific St, Box 356310, Seattle, WA 98195-6310, USA
    • ,
  • Craig R. Hampton, MD

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Wash, USA
    • ,
  • Albert J. Chong, MD

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Wash, USA
    • ,
  • Hiroo Takayama, MD

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Wash, USA
    • ,
  • Christine L. Rothnie, BS

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Wash, USA
    • ,
  • Denise J. Spring, PhD

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Wash, USA
    • ,
  • Hideto Shimpo, MD, PhD

      Affiliations

    • Department of Thoracic & Cardiovascular Surgery, Mie University School of Medicine, Tsu, Japan
    • ,
  • Isao Yada, MD, PhD

      Affiliations

    • Department of Thoracic & Cardiovascular Surgery, Mie University School of Medicine, Tsu, Japan
    • ,
  • Timothy H. Pohlman, MD

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Wash, USA
    • ,
  • Edward D. Verrier, MD

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Wash, USA

Received 21 October 2003 ,Revised 16 January 2004 ,Accepted 2 February 2004.

  • Image Result

    FR167653 blocks myocardial ischemia-reperfusion. CD-1 mice were subjected to myocardial ischemia-reperfusion injury, and area at risk (AAR) as a percentage of left ventricle (LV) and infarct size as a

    FR167653 blocks myocardial ischemia-reperfusion. CD-1 mice were subjected to myocardial ischemia-reperfusion injury, and area at risk (AAR) as a percentage of left ventricle (LV) and infarct size as a percentage of area at risk were determined as described in Materials and Methods section for control mice that received vehicle alone (cross-hatched bars) or vehicle with FR167653 (FR, 2 mg/kg, black bars). Values represent mean ± SD of 5 animals; asterisk indicates P < .01 versus vehicle.

  • Image Result
    Effects of FR167653 (FR) on myocardial MAPK activation after ischemia-reperfusion. Western blotting analyses of phospho-JNK and total JNK (A), ERK (B), and p38 MAPK (C) expressions. D, Phosphorylation

    Effects of FR167653 (FR) on myocardial MAPK activation after ischemia-reperfusion. Western blotting analyses of phospho-JNK and total JNK (A), ERK (B), and p38 MAPK (C) expressions. D, Phosphorylation of MAPKs. Values represent mean ± SD of 5 animals; asterisk indicates P < .001 versus control; dagger indicates P < .05 versus vehicle.

  • Image Result
    Effects of FR167653 (FR) on myocardial p38 MAPK activity after ischemia-reperfusion. A, Western blotting analysis of phospho-ATF-2 expression after immunoprecipitation and kinase assay for p38 MAPK ac

    Effects of FR167653 (FR) on myocardial p38 MAPK activity after ischemia-reperfusion. A, Western blotting analysis of phospho-ATF-2 expression after immunoprecipitation and kinase assay for p38 MAPK activity. B, p38 MAPK activities. Values represent mean ± SD of 5 animals; asterisk indicates P < .001 versus control; dagger indicates P < .05 versus vehicle.

  • Image Result
    Effects of p38 MAPK inhibition by FR167653 (FR) on myocardial NF-κB activation after ischemia-reperfusion. A, Electrophoretic mobility shift assay of NF-κB activation. B, Western blotting analysis of

    Effects of p38 MAPK inhibition by FR167653 (FR) on myocardial NF-κB activation after ischemia-reperfusion. A, Electrophoretic mobility shift assay of NF-κB activation. B, Western blotting analysis of phospho-IκBα expression as indirect indicator of NF-κB activation. C, NF-κB activities and phosphorylation of IκBα. Values represent mean ± SD of 5 animals; asterisk indicates P < .001 versus control; dagger indicates P < .05 versus vehicle.

  • Image Result
    Effects of p38 MAPK inhibition by FR167653 (FR) on myocardial inflammatory cytokine gene expression after ischemia-reperfusion. A, Ribonuclease protection assay of TNF-α, IL-1β, MCP-1, and glyceraldeh

    Effects of p38 MAPK inhibition by FR167653 (FR) on myocardial inflammatory cytokine gene expression after ischemia-reperfusion. A, Ribonuclease protection assay of TNF-α, IL-1β, MCP-1, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, internal control) mRNA expressions. B, Vertical axis denotes multiplicity of increase relative to control after amount of mRNA for each cytokine was normalized to that of glyceraldehyde-3-phosphate dehydrogenase mRNA. Values represent mean ± SD of 5 animals; asterisk indicates P < .05 versus control; dagger indicates P < .05 versus vehicle.

☆ Supported in part by the National Institutes of Health grant 5R01HL061762 and a Grant-in-Aid for Scientific Research (No. 14370408) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

PII: S0022-5223(04)00261-2

doi: 10.1016/j.jtcvs.2004.02.007

The Journal of Thoracic and Cardiovascular Surgery
Volume 128, Issue 4 , Pages 588-594 , October 2004

Article Tools

* Image Usage & Resolution