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Article
Mdivi-1 exerts cardioprotective effects in myocardial ischemia/reperfusion (MI/R) when given at reperfusion.
Research Day
  • Devon Stutzman, Philadelphia College of Osteopathic Medicine
  • Carly Schmidgall
  • Israel Benjamin, Philadelphia College of Osteopathic Medicine
  • Qian Chen, Philadelphia College of Osteopathic Medicine
  • Cathy Hatcher, Philadelphia College of Osteopathic Medicine
  • Robert Barsotti, Philadelphia College of Osteopathic Medicine
  • Lindon Young, Philadelphia College of Osteopathic Medicine
Location
Philadelphia
Start Date
13-5-2015 1:00 PM
Disciplines
Description
MI/R results in cardiac contractile dysfunction and increased cell death. MI/R is initiated in part by uncoupling of the electron transport chain in mitochondria, which generates reactive oxygen species (ROS). Increased ROS lead to the loss of mitochondrial membrane potential, which augments mitochondrial fission in MI/R. Mitochondrial fission is in turn associated with shortening of mitochondria, decreased ATP production, and is thought to promote cardiac contractile dysfunction and post reperfused cardiomyocyte loss, leading to increased infarct size. Therefore, inhibiting mitochondrial fission may be an effective new strategy to salvage injured cardiac myocytes during MI/R. Mdivi-1 (MW= 353 g/mol), a mitochondrial fission inhibitor, that acts by selectively inhibiting dynamin related protein 1, a GTPase that promotes mitochondrial fission via interaction with outer mitochondrial membrane proteins, was used to test this strategy. Isolated perfused rat hearts subjected to I (30 min)/R (90 min) were infused with Mdivi-1 (25 µM) given for 5 min following ischemia. Mdivi-1 treated hearts (n=6) significantly reduced infarct size to 25% ± 2%, as compared to control I/R hearts (n=9) 44% ± 4% (p< 0.01). However, Mdivi-1 treatment only transiently improved post-reperfused cardiac function at this dose. These preliminary results suggest that inhibition of mitochondrial fission reduces infarct size. Future studies will test other treatment regimens with Mdivi-1.
Citation Information
Devon Stutzman, Carly Schmidgall, Israel Benjamin, Qian Chen, et al.. "Mdivi-1 exerts cardioprotective effects in myocardial ischemia/reperfusion (MI/R) when given at reperfusion." (2015)
Available at: http://works.bepress.com/qian_chen/36/