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Since blood loss during surgery contributes to the pathogenesis of hyponatremia, we explored the effect of bleeding on plasma sodium using a controlled hypotensive hemorrhage pig model. After 30\u2010min baseline period, hemorrhage was induced by aspiration of blood during 30\u2009min at mean arterial pressure &lt;50\u2009mmHg. Thereafter, the animals were resuscitated with retransfused blood and a near\u2010isotonic balanced crystalloid solution and monitored for 180\u2009min. Electrolyte and water balances, cardiovascular response, renal hemodynamics, and markers of volume regulation and osmoregulation were investigated. All pigs (<jats:italic>n<\/jats:italic>\u2009=\u200910) developed hyponatremia. All animals retained hypotonic fluid, and none could excrete net\u2010free water. Urinary excretion of aquaporin 2, a surrogate marker of collecting duct responsiveness to antidiuretic hormone, was significantly reduced at the end of the study, whereas lysine vasopressin, i.e., the pig antidiuretic hormone remained high. In this animal model, hyponatremia developed due to net positive fluid balance and generation of electrolyte\u2010free water by the kidneys. A decreased urinary aquaporin 2 excretion may indicate an escape from antidiuresis.<\/jats:p>","DOI":"10.14814\/phy2.15886","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:48:21Z","timestamp":1701132501000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of controlled hypotensive hemorrhage on plasma sodium levels in anesthetized pigs: An exploratory study"],"prefix":"10.14814","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2759-5756","authenticated-orcid":false,"given":"Rafael T.","family":"Krmar","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Karolinska Institutet  Stockholm 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