Letson, Hayley, Morris, Jodie, and Dobson, Geoffrey (2023) Changes in plasma alpha-1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation. Pharmacology Research & Perspectives, 11 (5). e01133.

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Abstract

Introduction: 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-times higher for pigs than rats. Since lidocaine strongly binds to serum alpha-1-acid glycoprotein (AGP), the aim of the study was to investigate the effect of hemorrhagic shock on levels of AGP in rats and pigs.

Materials and Methods: Healthy adult male Sprague–Dawley rats and female crossbred pigs (n = 33 each) underwent tail vein and peripheral ear vein blood sampling, respectively, to collect plasma for AGP measurements. Rats (n = 17) and pigs (n = 16) underwent surgical instrumentation and uncontrolled hemorrhage via liver resection, and were treated with 3% NaCl ± ALM IV bolus followed 60 min later by 4 h 0.9% NaCl ± ALM IV drip. Rats were monitored for 72 h with blood samples taken post-surgery, and at 5.25, 24, and 72 h. Pigs were monitored for 6 h with blood samples taken post-surgery, and at 60 min and 6 h. Plasma AGP was measured with rat- and pig-specific enzyme-linked immunosorbent assay kits.

Results: Baseline AGP levels in rats were 3.91 μg/mL and significantly 83-fold lower than in pigs (325 μg/mL). Surgical instrumentation was associated with ~10-fold increases in AGP in rats and a 21% fall in pigs. AGP levels remained elevated in rats after hemorrhage and resuscitation (28–29 μg/mL). In contrast, no significant differences in plasma AGP were found in ALM- or Saline-treated pigs over the monitoring period.

Conclusions: 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.

Item ID:	80229
Item Type:	Article (Research - C1)
ISSN:	2052-1707
Keywords:	ALM; alpha-1 acid glycoprotein; hemorrhage; serum proteins; trauma
Copyright Information:	© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Funders:	USAMRMC
Projects and Grants:	SO150053 under Award W81XWH-USSOCOM-BAA-15-1, SO130004 under Award W81XWH-15-1-0002
Date Deposited:	30 Aug 2023 02:25
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3214 Pharmacology and pharmaceutical sciences > 321499 Pharmacology and pharmaceutical sciences not elsewhere classified @ 60% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320207 Emergency medicine @ 10% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3299 Other biomedical and clinical sciences > 329999 Other biomedical and clinical sciences not elsewhere classified @ 30%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200102 Efficacy of medications @ 100%
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