{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:06:54Z","timestamp":1753870014941,"version":"3.41.2"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T00:00:00Z","timestamp":1693267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The binding of drugs to plasma proteins is an important consideration in drug development. We have reported that the dose of adenosine, lidocaine, and magnesium (ALM) fluid therapy for resuscitation from hemorrhagic shock is nearly 3\u2010times higher for pigs than rats. Since lidocaine strongly binds to serum alpha\u20101\u2010acid glycoprotein (AGP), the aim of the study was to investigate the effect of hemorrhagic shock on levels of AGP in rats and pigs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Healthy adult male Sprague\u2013Dawley rats and female crossbred pigs (<jats:italic>n<\/jats:italic>\u2009=\u200933 each) underwent tail vein and peripheral ear vein blood sampling, respectively, to collect plasma for AGP measurements. Rats (<jats:italic>n<\/jats:italic>\u2009=\u200917) and pigs (<jats:italic>n<\/jats:italic>\u2009=\u200916) underwent surgical instrumentation and uncontrolled hemorrhage via liver resection, and were treated with 3% NaCl\u2009\u00b1\u2009ALM IV bolus followed 60\u2009min later by 4\u2009h 0.9% NaCl\u2009\u00b1\u2009ALM IV drip. Rats were monitored for 72\u2009h with blood samples taken post\u2010surgery, and at 5.25, 24, and 72\u2009h. Pigs were monitored for 6\u2009h with blood samples taken post\u2010surgery, and at 60\u2009min and 6\u2009h. Plasma AGP was measured with rat\u2010 and pig\u2010specific enzyme\u2010linked immunosorbent assay kits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Baseline AGP levels in rats were 3.91\u2009\u03bcg\/mL and significantly 83\u2010fold lower than in pigs (325\u2009\u03bcg\/mL). Surgical instrumentation was associated with ~10\u2010fold increases in AGP in rats and a 21% fall in pigs. AGP levels remained elevated in rats after hemorrhage and resuscitation (28\u201329\u2009\u03bcg\/mL). In contrast, no significant differences in plasma AGP were found in ALM\u2010 or Saline\u2010treated pigs over the monitoring period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that the trauma of surgery alone was associated with significant increases in AGP in rats, compared to a contrasting decrease in pigs. Higher levels of plasma AGP in pigs prior to hemorrhagic shock is consistent with the higher ALM doses required to resuscitate pigs compared with rats.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prp2.1133","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T23:49:21Z","timestamp":1693352961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in plasma alpha\u20101 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of <scp>ALM<\/scp> drug therapy in rat and pig resuscitation"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0135-134X","authenticated-orcid":false,"given":"Hayley L.","family":"Letson","sequence":"first","affiliation":[{"name":"Heart and Trauma Research Laboratory, College of Medicine and Dentistry James Cook University  Townsville Queensland 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