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Determination of regional coronary flow utilizing microspheres in ex vivo myocardial ischemia/reperfusion (MI/R) injury
Research Day
  • Tarah Kuhn, Philadelphia College of Osteopathic Medicine
  • Sabrina Clark
  • Andrew Castellano
  • Daniel Kuo
  • Stephanie Liu
  • Qian Chen
  • Robert Barsotti
Start Date
11-5-2016 1:00 PM
MI/R results in marked cardiac contractile dysfunction and cell death. We previously discovered that protein kinase C epsilon peptide inhibitor (PKC ε-) robustly restored post-reperfused cardiac function, and reduced infarct size, oxidative stress, and leukocyte endothelial interactions in coronary, hind limb, renal, and mesenteric vascular inflammation models. The mechanisms of these effects in part are due to attenuating uncoupled endothelial nitric oxide (NO) synthase activity and increase endothelial NO bioavailability. Therefore, we hypothesize that PKC ε- will increase regional flow during reperfusion. We determined regional flow to the right ventricle, left ventricle, and septum at baseline and after 10 and 45 min reperfusion using fluorescent microspheres in isolated rat perfused hearts subjected to global I(30min)/R(45min). A cell permeable PKC ε- (myr-EAVSLKPT, MW=1054 g/mol, 10μM, n=8) was given at beginning of reperfusion for 5 min. We found that final left ventricular developed pressure (LVDP) recovered to 70 ± 7%, maximal rate of left ventricular contraction, +dP/dtmax to 57 ± 7% and maximal rate of left ventricular relaxation, -dP/dtmin to 58 ± 6% of baseline values. These parameters were significantly improved compared to untreated I/R hearts (n=7) that only recovered to 30 ± 5% in LVDP, 21 ± 5% in dP/dtmax and 25 ± 5% in dP/dtmin relative to baseline values (all p < 0.01). Moreover, our preliminary data suggest that PKC ε- treatment increased regional flow by 190 ± 40% in the right ventricle, 140 ± 30% in the left ventricle, and 120 ± 20% in the septum at 10 min. post reperfusion compared to non-treated control MI/R hearts. These values were maintained throughout the remaining 35 min of reperfusion. In summary, the data indicates that PKC ε- improves postreperfused cardiac function in part by restoration of regional flow.
Citation Information
Tarah Kuhn, Sabrina Clark, Andrew Castellano, Daniel Kuo, et al.. "Determination of regional coronary flow utilizing microspheres in ex vivo myocardial ischemia/reperfusion (MI/R) injury" (2016)
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