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However, it remains unknown how TH regulates metabolic recovery. We tested the hypothesis that TH modulates PTEN, Akt, and ERK1\/2, and improves metabolic recovery through mitigation of fatty acid oxidation and taurine release. Left ventricular function was monitored continuously in isolated rat hearts subjected to 20\u2009min of global, no\u2010flow ischemia. Moderate cooling (30\u00b0C) was applied at the start of ischemia and hearts were rewarmed after 10\u00a0min of reperfusion. The effect of TH on protein phosphorylation and expression at 0 and 30\u2009min of reperfusion was investigated by western blot analysis. Post\u2010ischemic cardiac metabolism was investigated by <jats:sup>13<\/jats:sup>C\u2010NMR. TH enhanced recovery of cardiac function, reduced taurine release, and enhanced PTEN phosphorylation and expression. Phosphorylation of Akt and ERK1\/2 was increased at the end of ischemia but decreased at the end of reperfusion. On NMR analysis, TH\u2010treated hearts displayed decreased fatty acid oxidation. Direct cardioprotection by moderate intra\u2010ischemic TH is associated with decreased fatty acid oxidation, reduced taurine release, enhanced PTEN phosphorylation and expression, and enhanced activation of both Akt and ERK1\/2 prior to reperfusion.<\/jats:p>","DOI":"10.14814\/phy2.15611","type":"journal-article","created":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T17:42:57Z","timestamp":1676742177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>Intra\u2010ischemic<\/scp> hypothermia cardioprotection involves modulation of <scp>PTEN<\/scp>\/Akt\/<scp>ERK<\/scp> signaling and fatty acid oxidation"],"prefix":"10.14814","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3734-511X","authenticated-orcid":false,"given":"Cody N.","family":"Justice","sequence":"first","affiliation":[{"name":"Center for Advanced Resuscitation Medicine, Department of Emergency Medicine University of Illinois at Chicago  Chicago Illinois USA"},{"name":"Department of Physiology and Biophysics University of Illinois at Chicago  Chicago Illinois USA"},{"name":"Center for Cardiovascular Research University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5627-8082","authenticated-orcid":false,"given":"Xiangdong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center for Advanced Resuscitation Medicine, Department of Emergency Medicine University of Illinois at Chicago  Chicago Illinois USA"},{"name":"Center for Cardiovascular Research University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Advanced Resuscitation Medicine, Department of Emergency Medicine University of Illinois at Chicago  Chicago Illinois USA"},{"name":"Center for Cardiovascular Research University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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