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Return of blood flow allows for the needed reperfusion; however, for a period of time before remaining viable cells stabilize, reperfusion results in additional cellular injury. In cardiomyocytes, loss of membrane integrity allows abnormal influx of extracellular calcium, leading to hyper\u2010contracture and cell death. Methods to improve the membrane integrity of cardiomyocytes overwhelmed by pathological disruptions, such as reperfusion injury, are needed to prevent cell death, because of the myocardium's limited ability to regenerate. Research has shown administration of the copolymer P(oloxamer) 188 before ischemia\/reperfusion can protect cardiomyocytes through membrane stabilization. This study sought to determine whether the administration of P188 at the beginning of the clinically more relevant time of reperfusion after ischemia will attenuate any additional damage to cardiomyocytes by stabilizing membrane integrity to allow the cells to maintain function. Using an in\u2010vitro cardiomyocyte model subjected to hypoxia\/reoxygenation to simulate ischemia\/reperfusion injury, we show that reoxygenation significantly potentiates the injury caused by hypoxia itself. P188, with its unique combination of hydrophobic and hydrophilic chemical properties, and only delivered at the beginning of reoxygenation, dose\u2010dependently protected cardiomyocytes from injury due to reoxygenation by repairing cell membranes, decreasing calcium influx, and maintaining cellular morphology. Our study also shows the hydrophobic portion of P188 is necessary for the stabilization of cell membrane integrity in providing protection to cardiomyocytes against reoxygenation injury.<\/jats:p>","DOI":"10.1002\/prp2.639","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T18:02:25Z","timestamp":1603130545000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Poloxamer 188 Protects Isolated Adult Mouse Cardiomyocytes from Reoxygenation Injury"],"prefix":"10.1002","volume":"8","author":[{"given":"Michele M.","family":"Salzman","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Vanderbilt University Medical Center Nashville TN USA"},{"name":"Department of Pharmacology Vanderbilt University Nashville TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason A.","family":"Bartos","sequence":"additional","affiliation":[{"name":"Department of Medicine \u2013 Cardiovascular Division University of Minnesota Minneapolis MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demetris","family":"Yannopoulos","sequence":"additional","affiliation":[{"name":"Department of Medicine \u2013 Cardiovascular Division University of Minnesota Minneapolis MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-5757","authenticated-orcid":false,"given":"Matthias L.","family":"Riess","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Vanderbilt University Medical Center Nashville TN USA"},{"name":"Department of Pharmacology Vanderbilt University Nashville TN USA"},{"name":"Department of Anesthesiology TVHS VA Medical Center Nashville TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1074248411409581"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394309-5.00006-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.12.008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13330"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs116"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.3.6.1035"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resuscitation.2012.04.005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2217\/fca.14.6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0265021505001080"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resuscitation.2014.09.019"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-010-0121-4"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt004"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/1872208311206030200"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1215368"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00321.2019"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(02)75499-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.5b11448"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.6b03030"},{"issue":"1069","key":"e_1_2_9_20_1","first-page":"11","article-title":"Poloxamer 188 decreases hypoxia\u2010reoxygenation\u2010induced LDH release from isolated human cardiomyocytes","volume":"31","author":"Salzman MM","year":"2017","journal-title":"FASEB J"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-013-1064-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.7b00419"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03844"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-017-1953-y"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(01)00404-5"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101386"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.2018.1432266"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41329"},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","unstructured":"AmaralE GuatimosinS GuatimosinC.Using the fluorescent styryl dye FM1\u201043 to visualize synaptic vescicles exocytosis and endocytosis in motor nerve terminals. 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