• Wessel W Fuijkschot, Martine C Morrison, Rianne van der Linden, Krijnen Paul A J PAJ Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research (ICaR-VU), VU University Med, Ilse P A Zethof, Theyse Lars F H LFH Department Clinical Sciences and Services, Royal Veterinary College London, University of London, United Kingdom., Robert Kleemann, Niessen Hans W M HWM Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research (ICaR-VU), VU University Med, and Yvo M Smulders.
• Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands; Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: w.fuijkschot@vumc.nl.
• Atherosclerosis. 2016 Dec 1; 255: 164-170.

Background And AimsObservational studies show a peak incidence of cardiovascular events after major surgery. For example, the risk of myocardial infarction increases 25-fold early after hip replacement. The acuteness of this increased risk suggests abrupt enhancement in plaque vulnerability, which may be related to intra-plaque inflammation, thinner fibrous cap and/or necrotic core expansion. We hypothesized that acute systemic inflammation following major orthopedic surgery induces such changes.MethodsApoE-/- mice were fed a western diet for 10 weeks. Thereafter, half the mice underwent mid-shaft femur osteotomy followed by realignment with an intramedullary K-wire, to mimic major orthopedic surgery. Mice were sacrificed 5 or 15 days post-surgery (n = 22) or post-saline injection (n = 13). Serum amyloid A (SAA) was measured as a marker of systemic inflammation. Paraffin embedded slides of the aortic root were stained to measure total plaque area and to quantify fibrosis, calcification, necrotic core, and inflammatory cells.ResultsSurgery mice showed a pronounced elevation of serum amyloid A (SAA) and developed increased plaque and necrotic core area already at 5 days, which reached significance at 15 days (p = 0.019; p = 0.004 for plaque and necrotic core, respectively). Macrophage and lymphocyte density significantly decreased in the surgery group compared to the control group at 15 days (p = 0.037; p = 0.024, respectively). The density of neutrophils and mast cells remained unchanged.ConclusionsMajor orthopedic surgery in ApoE-/- mice triggers a systemic inflammatory response. Atherosclerotic plaque area is enlarged after surgery mainly due to an increase of the necrotic core. The role of intra-plaque inflammation in this response to surgical injury remains to be fully elucidated.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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