Determination of Regional Flow Utilizing Microspheres in ex vivo Myocardial Ischemia/Reperfusion (MI/R) Injury

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MI/R results in marked cardiac contractile dysfunction and cell death. We previously discovered that protein kinase C epsilon peptide inhibitor (PKC e-) robustly restored postreperfused 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 increasing endothelial NO bioavailability. Therefore, we hypothesize that PKC e- 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 perfused rat hearts subjected to global I(30min)/R(45min). A cell permeable PKC e-(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 control 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 e- 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 postreperfusion compared to untreated control I/R hearts. These values were maintained throughout the remaining 35 min of reperfusion. In summary, the data indicates that PKC e- improves postreperfused cardiac function in part by restoration of regional flow.

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The FASEB Journal




1 Supplement

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This article was published in The FASEB Journal, Volume 30, Issue 1 Supplement, Pages 1278.9-1278.9.

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