Clin Res Cardiol 98, Suppl 1, April 2009

V239 - Myeloperoxidase - Einfluss auf den Gefäßtonus und die Myokardperfusion am Schweinemodell
S. Wipper1, B. Reiter1, C. Detter1, K. Knöll1, M. Kolk1, C. Pahrmann1, H. Wieboldt2, K. Wegscheider3, T. Meinertz2, H. Reichenspurner1, S. Baldus2
1Klinik und Poliklinik für Herz- und Gefäßchirurgie, Universitäres Herzzentrum Hamburg gGmbH, Hamburg; 2Klinik und Poliklinik für Kardiologie/Angiologie, Universitäres Herzzentrum Hamburg gGmbH, Hamburg; 3Institut für Medizinische Biometrie und Epidemiologie, Universitätsklinikum Hamburg Eppendorf, Hamburg;
Background: Ex-vivo studies suggest that myeloperoxidase (MPO), a heme protein abundantly expressed and released by activated neutrophils, oxidizes endothelial-derived nitric oxide (NO). Whether free MPO affects vascular tone in a leukocyte-independent manner in-vivo however remains elusive.
Methods and Results: Human MPO and human serum albumine (HSA, 18µg/kg BW each), respectively was injected into the left atrium of open chest, continuously paced pigs (n=16, 56±6kg) in a blinded randomized manner. Internal mammaria artery (IMA) and LAD blood flow was assessed using a doppler flow probe (TTFM). Myocardial perfusion was quantified by Fluorescent Microspheres (FM) and Fluorescent Cardiac Imaging (FCI). Following MPO bolus administration, MPO plasma levels peaked immediately (1min: 1115±453pmol/l) and rapidly declined thereafter (5min:295±132; 90min:4±6.8 pmol/l), reflecting rapid binding of MPO to the vessel wall. LAD (mean decrease per 30min was 7.5(95%CI:4.1 to 10.9)ml/min, p<0.001)  and IMA flow (mean decrease per 30min was 30.2(95%CI: 22.5 to 37.9)ml/min, p<0.001) decreased following MPO application as did myocardial perfusion (90min:1.48±0.25 vs 2.3±0.64ml/min/g in controls p<0.05).  Explanted IMA-rings from animals subjected to MPO not only revealed markedly reduced relaxation in response to acetylcholine (56.9 vs.89.4% for controls, p<0.01), addition of the MPO substrate hydrogen peroxide further attenuated NO-dependent relaxation in vessels from MPO-treated animals as opposed to controls (TAGfontoffTAGsymfontDTAGfontoffTAGstdfontpre/post H2O2: -11.5 vs.+0.1%, p<0.01).
Conclusions: Administration of free MPO elicts profound systemic changes in vascular tone of conductance and resistance vessels. Thus MPO emerges as a key enzyme by which leukocytes are capable of modulating vascular tone remote of their site of degranulation.