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Ischemia\/reperfusion injury from HS resuscitation can be exaggerated by TBI-induced loss of autoregulation. In HS resuscitation, the goal is to restore lost blood volume, while in the treatment of TBI the priority is focused on maintenance of adequate cerebral perfusion pressure and avoidance of secondary bleeding. In this study, we investigate the responses to resuscitation from severe HS after TBI in rats, using fresh blood, polymerized human hemoglobin (PolyhHb), and lactated Ringer\u2019s (LR). Rats were subjected to TBI by pneumatic controlled cortical impact. Shortly after TBI, HS was induced by blood withdrawal to reduce mean arterial pressure (MAP) to 35\u201340\u00a0mmHg for 90\u00a0min before resuscitation. Resuscitation fluids were delivered to restore MAP to ~\u200965\u00a0mmHg and animals were monitored for 120\u00a0min. Increased systolic blood pressure variability (SBPV) confirmed TBI-induced loss of autoregulation. MAP after resuscitation was significantly higher in the blood and PolyhHb groups compared to the LR group. Furthermore, blood and PolyhHb restored diastolic pressure, while this remained depressed for the LR group, indicating a loss of vascular tone. Lactate increased in all groups during HS, and only returned to baseline level in the blood reperfused group. The PolyhHb group possessed lower SBPV compared to LR and blood groups. Finally, sympathetic nervous system (SNS) modulation was higher for the LR group and lower for the PolyhHb group compared to the blood group after reperfusion. In conclusion, our results suggest that PolyhHb could be an alternative to blood for resuscitation from HS after TBI when blood is not available, assuming additional testing demonstrate similar favorable results. PolyhHb restored hemodynamics and oxygen delivery, without the logistical constraints of refrigerated blood.<\/jats:p>","DOI":"10.1038\/s41598-021-81717-3","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T11:04:39Z","timestamp":1611831879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Resuscitation from hemorrhagic shock after traumatic brain injury with polymerized hemoglobin"],"prefix":"10.1038","volume":"11","author":[{"given":"Cynthia R.","family":"Muller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Courelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander T.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce B.","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton T.","family":"Cuddington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah R.","family":"Moses","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre F.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik B.","family":"Kistler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Cabrales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"81717_CR1","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1001\/archsurg.136.10.1118","volume":"136","author":"G Manley","year":"2001","unstructured":"Manley, G. et al. 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