{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T03:50:13Z","timestamp":1769572213825,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T00:00:00Z","timestamp":1574294400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002839","name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002839","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005970","name":"Deutsche Stiftung f\u00fcr Herzforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005970","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2019,11,21]]},"abstract":"<jats:p><jats:italic>Introduction<\/jats:italic>. Fever is frequently observed after acute ischemic events and is associated with poor outcome and higher mortality. Targeted temperature management (TTM) is recommended for neuroprotection in comatose cardiac arrest survivors, but pyrexia after rewarming is proven to be detrimental in clinical trials. However, the cellular mechanisms and kinetics of post-TTM rebound pyrexia remain to be elucidated. Therefore, we investigated the effects of cooling and post-TTM pyrexia on the inflammatory response and apoptosis in a cardiomyocyte ischemia-reperfusion (IR) injury model. <jats:italic>Methods<\/jats:italic>. HL-1 cardiomyocytes were divided into the following groups to investigate the effect of oxygen-glucose deprivation\/reperfusion (OGD\/R), hypothermia (33.5\u00b0C), and pyrexia (40\u00b0C): normoxia controls maintained at 37\u00b0C and warmed to 40\u00b0C, OGD\/R groups maintained at 37\u00b0C and cooled to 33.5\u00b0C for 24\u2009h with rewarming to 37\u00b0C, and OGD\/R pyrexia groups further warmed from 37 to 40\u00b0C. Caspase-3 and RBM3 were assessed by Western blot and TNF-<jats:italic>\u03b1<\/jats:italic>, IL-6, IL-1<jats:italic>\u03b2<\/jats:italic>, SOCS3, iNOS, and RBM3 transcriptions by RT-qPCR. <jats:italic>Results<\/jats:italic>. OGD-induced oxidative stress (iNOS) in cardiomyocytes was attenuated post-TTM by cooling. Cytokine transcriptions were suppressed by OGD, while reperfusion induced significant TNF-<jats:italic>\u03b1<\/jats:italic> transcription that was exacerbated by cooling. Significant inductions of TNF-<jats:italic>\u03b1<\/jats:italic>, IL-6, IL-1<jats:italic>\u03b2<\/jats:italic>, and SOCS3 were observed in noncooled, but not in cooled and rewarmed, OGD\/R-injured cardiomyocytes. Further warming to pyrexia induced a sterile inflammatory response in OGD\/R-injured groups that was attenuated by previous cooling, but no inflammation was observed in pyrexic normoxia groups. Moreover, cytoprotective RBM3 expression was induced by cooling but suppressed by pyrexia, correlating with apoptotic caspase-3 activation. <jats:italic>Conclusion<\/jats:italic>. Our findings show that maintaining a period of post-TTM \u201ctherapeutic normothermia\u201d is effective in preventing secondary apoptosis-driven myocardial cell death, thus minimizing the infarct area and further release of mediators of the innate sterile inflammatory response after acute IR injury.<\/jats:p>","DOI":"10.1155\/2019\/6431957","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T18:31:09Z","timestamp":1574361069000},"page":"1-10","source":"Crossref","is-referenced-by-count":7,"title":["Post-TTM Rebound Pyrexia after Ischemia-Reperfusion Injury Results in Sterile Inflammation and Apoptosis in Cardiomyocytes"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-9750","authenticated-orcid":true,"given":"Giang","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Congenital Heart Disease\/Pediatric Cardiology, Universit\u00e4res Herzzentrum Berlin-Medical Heart Center of Charit\u00e9 and German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nalina N. A.","family":"von Garlen","sequence":"additional","affiliation":[{"name":"Department of Congenital Heart Disease\/Pediatric Cardiology, Universit\u00e4res Herzzentrum Berlin-Medical Heart Center of Charit\u00e9 and German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia J.","family":"Wowro","sequence":"additional","affiliation":[{"name":"Department of Congenital Heart Disease\/Pediatric Cardiology, Universit\u00e4res Herzzentrum Berlin-Medical Heart Center of Charit\u00e9 and German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phuong D.","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Congenital Heart Disease\/Pediatric Cardiology, Universit\u00e4res Herzzentrum Berlin-Medical Heart Center of Charit\u00e9 and German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Krech","sequence":"additional","affiliation":[{"name":"Department of Congenital Heart Disease\/Pediatric Cardiology, Universit\u00e4res Herzzentrum Berlin-Medical Heart Center of Charit\u00e9 and German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Congenital Heart Disease\/Pediatric Cardiology, Universit\u00e4res Herzzentrum Berlin-Medical Heart Center of Charit\u00e9 and German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Department of Pediatric Cardiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina R. 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