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Combinational Effects of gp91 ds-tat and SS-31 in Reducing Myocardial/ischemia Reperfusion (MI/R) Injury
Research Day
  • H. Patel, Philadelphia College of Osteopathic Medicine
  • Sara Ferry Walker, Philadelphia College of Osteopathic Medicine
  • William Chau, Philadelphia College of Osteopathic Medicine
  • Issachar Devine, Philadelphia College of Osteopathic Medicine
  • Regina Ondrasik, Philadelphia College of Osteopathic Medicine
  • Qian Chen, Philadelphia College of Osteopathic Medicine
  • Robert J. Barsotti, Philadelphia College of Osteopathic Medicine
  • Lindon H. Young, Philadelphia College of Osteopathic Medicine
Location
Philadelphia Campus
Start Date
7-5-2014 1:00 PM
Description

MI/R injury results in cardiac contractile dysfunction, and increased cell death principally due to the reperfusion of blood following ischemia. This injury is initiated in part by a decrease in endothelial derived nitric oxide bioavailability and an increase in reactive oxygen species (ROS). Two key sources of ROS are NADPH oxidase and damaged mitochondria. We’ve shown that gp91 ds-tat, a NADPH oxidase assembly inhibitor peptide and SS-31, a mitochondrial targeted antioxidant, dose dependently improved post-reperfused left ventricular developed pressure (LVDP) and reduced infarct size in rat hearts subjected to I (30min)/R (45min). This led us to the question, whether the combinational effects of low dose gp91 ds-tat and SS-31 would act synergistically to improve LVDP and reduce infarct size compared to the independent effects of each peptide and untreated control? Early data show that the combination of gp91 ds-tat (5μM) + SS31 (10μM) (n=3) improved post-reperfused LVDP by 63 ± 11% of baseline and reduced infarct size (IS) to 32 ± 9% compared to control (44 ± 10% of baseline, n=7; 42 ± 5% IS) and to SS-31 10μM (25 ± 1% of baseline, n=3; 41 ± 10% IS); gp91 5μM (56 ± 9% of baseline, n=6; 28 ± 5% IS). Although this combination improved post-reperfused LVDP more so than either drug alone or control, at these concentrations the combinations didn’t act synergistically. Other combinational doses will be tested in the future.

Citation Information
H. Patel, Sara Ferry Walker, William Chau, Issachar Devine, et al.. "Combinational Effects of gp91 ds-tat and SS-31 in Reducing Myocardial/ischemia Reperfusion (MI/R) Injury" (2014)
Available at: http://works.bepress.com/qian_chen/28/