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Impaired autophagy leads to heart failure and mitophagy is important for mitigating ischemia\/reperfusion injury. This study aims to investigate whether the beneficial effects of therapeutic hypothermia are due to preserved autophagy and mitophagy. Under general anesthesia, the left anterior descending coronary artery of 19 female farm pigs was occluded for 90\u2009minutes with consecutive reperfusion. 30\u2009minutes after reperfusion, we performed pericardial irrigation with warm or cold saline for 60\u2009minutes. Myocardial tissue analysis was performed one and four weeks after infarction. Therapeutic hypothermia induced a significant increase in autophagic flux, mitophagy, mitochondrial mass and function in the myocardium after infarction. Cell stress, apoptosis, inflammation as well as fibrosis were reduced, with significant preservation of systolic and diastolic function four weeks post infarction. We found similar biochemical changes in human samples undergoing open chest surgery under hypothermic conditions when compared to the warm. These results suggest that autophagic flux and mitophagy are important mechanisms implicated in cardiomyocyte recovery after myocardial infarction under hypothermic conditions. New therapeutic strategies targeting these pathways directly could lead to improvements in prevention of heart failure.<\/jats:p>","DOI":"10.1038\/s41598-019-46452-w","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T10:03:11Z","timestamp":1562752991000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Myocardial hypothermia increases autophagic flux, mitochondrial mass and myocardial function after ischemia-reperfusion injury"],"prefix":"10.1038","volume":"9","author":[{"given":"Stefanie","family":"Marek-Iannucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandine","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annunziata","family":"Crupi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Sin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5744-2625","authenticated-orcid":false,"given":"Lawrence S.","family":"Czer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fardad","family":"Esmailian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Robert M.","family":"Mentzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen M.","family":"Andres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1432-006X","authenticated-orcid":false,"given":"Roberta A.","family":"Gottlieb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,10]]},"reference":[{"key":"46452_CR1","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1056\/NEJMoa012689","volume":"346","author":"Hypothermia after Cardiac Arrest Study Group","year":"2002","unstructured":"Hypothermia after Cardiac Arrest Study Group. 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