{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:48:05Z","timestamp":1787748485990,"version":"build-2784847793"},"reference-count":52,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":2329,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:p>Myocardial infarction and stroke are frequent after surgical procedures and consume a considerable amount of benefit of surgical therapy. Perioperative stress, induced by surgery, is composed of hemodynamic and inflammatory reactions. The effects of perioperative stress on atherosclerotic plaques are ill-defined. Murine models to investigate the influence of perioperative stress on plaque stability and rupture are not available. We developed a model to investigate the influence of perioperative stress on plaque growth and stability by exposing apolipoprotein E-deficient mice, fed a high cholesterol diet for 7 weeks, to a double hit consisting of 30 minutes of laparotomy combined with a substantial blood loss (20% body weight; 400\u00b5l). The innominate artery was harvested 72 hours after the intervention. Control groups were sham and baseline controls. Interleukin-6 (IL-6) and Serum Amyloid A plasma levels were determined. Plaque load VSMC- and macrophage-content were quantified. Plaque stability was assessed using the Stary score and frequency of signs of plaque rupture. High-dose atorvastatin (80\u2005mg\/kg body weight\/day) was administered for 6 days starting 3 days prior to double hit. A single dose of an IL-6-neutralizing antibody or the fusion protein sgp130-Fc selectively targeting IL-6 trans-signaling was subcutaneously injected. IL-6 plasma levels increased peaking at 6h after the intervention. SAA levels peaked at 24 hours (n=4, p&amp;lt;0.01). Plaque volume increased significantly with the double hit compared to sham (n=8, p&amp;lt;0.01). More plaques were scored as complex or bearing signs of rupture after the double hit compared to sham (n=5-8, p&amp;lt;0.05). Relative VSMC and macrophage content remained unchanged. IL-6-inhibition or atorvastatin, but not blocking of IL-6 trans-signaling, significantly decreased plaque volume and complexity (n=8, p&amp;lt;0.01),<\/jats:p>\n               <jats:p>Using this model, researchers will be able to further investigate the pathophysiology of perioperative plaque stability, which can result in myocardial infarction, and additionally, to test potential protective strategies.<\/jats:p>","DOI":"10.1242\/dmm.018713","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T02:47:05Z","timestamp":1434682025000},"source":"Crossref","is-referenced-by-count":15,"title":["Acute perioperative stress-induced increase of plaque volume and vulnerability in apolipoprotein E-deficient mice is amenable to statin treatment and IL-6-inhibition"],"prefix":"10.1242","author":[{"given":"Henrike","family":"Janssen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany"},{"name":"Department of Anesthesiology at the University of Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian S.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Demmer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Callies","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesine","family":"S\u00f6lter","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houra Loghmani","family":"Kouzhani","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niandan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Schuett","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Marburg, Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe J.F.","family":"Tietge","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Groningen, UMCG, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Warnecke","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, German Centre for Lung Research (DZL), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Larmann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany"},{"name":"Department of Anesthesiology at the University of Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Theilmeier","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany"},{"name":"Dept of Health Services Sciences, University of Oldenburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042501230690100_DMM018713C1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1056\/NEJM199201023260101","article-title":"Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery","volume":"326","author":"Anand","year":"1992","journal-title":"N. 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