Circ Cardiovasc Interv

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Circ Cardiovasc Interv Treatment With OPN-305, a Humanized Anti–Toll-Like Receptor-2 Antibody, Reduces Myocardial Ischemia/Reperfusion Injury in Pigs by Fatih Arslan, Jaco H. Houtgraaf, Brian Keogh, Kushan Kazemi, Renate de Jong, William J. McCormack, Luke A.J. O'Neill, Peter McGuirk, Leo Timmers, Mirjam B. Smeets, Lars Akeroyd, Mary Reilly, Gerard Pasterkamp, and Dominique P.V. de Kleijn Circ Cardiovasc Interv Volume 5(2):279-287 April 17, 2012 Copyright © American Heart Association, Inc. All rights reserved.

A simplified illustration of infarct size and area at risk (AAR) assessment. A simplified illustration of infarct size and area at risk (AAR) assessment. A, Cross section of the left ventricle with perfusion areas of the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCx). B, Ligation of the LCx results in ischemia of the area behind the ligature, as illustrated by bleaching of the myocardium. This is the endangered myocardium, also known as the AAR, in which cell death (ie, infarction) will occur. Note the border zones between the LAD and LCx perfusion areas, where a gradient of ischemia exists. In these areas, there is no absolute ischemia. C, After releasing the ligature, reperfusion occurs in the LCx perfusion area as illustrated by the darker red color representing hyperemia, a typical characteristic of reperfusion after ischemia. D, Twenty-four hours after reperfusion, the LCx is ligated again at the level marked by a piece of suture left in place. Hereafter, Evans blue dye is injected into the left ventricle. This results in coloring of all perfusion areas, except behind the LCx ligation (the ligature prevents the dye entering the LCx perfusion area). Finally, the infarcted areas appear white, whereas viable myocardium stains red after TTC treatment. Fatih Arslan et al. Circ Cardiovasc Interv. 2012;5:279-287 Copyright © American Heart Association, Inc. All rights reserved.

Binding and half-life of OPN-305. Binding and half-life of OPN-305. A, OPN-305, detected by FACS, binds to porcine peripheral blood mononuclear cells (2 individual porcine samples). B, Plasma concentration of OPN-305 at 25 mg/kg, 12.5 mg/kg and 6.25 mg/kg doses after single bolus administration. Each bar represents Mean±SEM, n=4/group for in vivo experiments. Fatih Arslan et al. Circ Cardiovasc Interv. 2012;5:279-287 Copyright © American Heart Association, Inc. All rights reserved.

OPN-305 reduces infarct size. OPN-305 reduces infarct size. A, Infarct size (IS) as a percentage of the area at risk (AAR); *P=0.041 compared with saline treatment. B, The extent of ischemic/reperfused myocardium as percentage of the left ventricle (AAR/LV). C, Infarct size measured by serum Troponin I levels 24 hours after reperfusion; *P=0.003 compared with saline treatment. D, Scatterplot illustrating the correlation between serum Troponin I levels and invasive infarct size staining. Pearson correlation 0.593 at P=0.001 level (E) white blood cell (WBC) counts 24 hours after reperfusion. Each bar represents mean±SEM, n=8 for saline, n=11 for 12.5 mg/kg, n=7 for 6.25 mg/kg, and n=6 for 1.56 mg/kg treated groups. Representative Evans blue dye and subsequent TTC-stained cross section of hearts are shown for each group. Fatih Arslan et al. Circ Cardiovasc Interv. 2012;5:279-287 Copyright © American Heart Association, Inc. All rights reserved.

OPN-305 improves systolic performance after ischemia/reperfusion injury. OPN-305 improves systolic performance after ischemia/reperfusion injury. Baseline and postinfarct (A) global ejection fractions (EF) are shown. B, Fractional shortening (FS); *P=0.013 compared with saline and †P=0.023 compared with 12.5 mg/kg treatment. C, Systolic wall thickening (SWT) of the infarcted myocardium; *P=0.006 and **P=0.021 compared with saline and †P=0.003 compared with 12.5 mg/kg treatment. D, Wall thickness (WT) of the infarcted myocardium. Each bar represents mean±SEM. Fatih Arslan et al. Circ Cardiovasc Interv. 2012;5:279-287 Copyright © American Heart Association, Inc. All rights reserved.