Changes in plasma alpha‐1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation
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 lidoc...
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.1133 |
| _version_ | 1797658944596869120 |
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| author | Hayley L. Letson Jodie L. Morris Geoffrey P. Dobson |
| author_facet | Hayley L. Letson Jodie L. Morris Geoffrey P. Dobson |
| author_sort | Hayley L. Letson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T18:06:45Z |
| format | Article |
| id | doaj.art-fc4bdd7d769e44359f0586de402a6c56 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-03-11T18:06:45Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-fc4bdd7d769e44359f0586de402a6c562023-10-17T07:30:29ZengWileyPharmacology Research & Perspectives2052-17072023-10-01115n/an/a10.1002/prp2.1133Changes in plasma alpha‐1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitationHayley L. Letson0Jodie L. Morris1Geoffrey P. Dobson2Heart and Trauma Research Laboratory, College of Medicine and Dentistry James Cook University Townsville Queensland AustraliaHeart and Trauma Research Laboratory, College of Medicine and Dentistry James Cook University Townsville Queensland AustraliaHeart and Trauma Research Laboratory, College of Medicine and Dentistry James Cook University Townsville Queensland AustraliaAbstract 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.https://doi.org/10.1002/prp2.1133ALMalpha‐1 acid glycoproteindosagehemorrhageserum proteinstrauma |
| spellingShingle | Hayley L. Letson Jodie L. Morris Geoffrey P. Dobson 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 ALM alpha‐1 acid glycoprotein dosage hemorrhage serum proteins trauma |
| title | Changes in plasma alpha‐1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation |
| title_full | Changes in plasma alpha‐1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation |
| title_fullStr | Changes in plasma alpha‐1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation |
| title_full_unstemmed | Changes in plasma alpha‐1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation |
| title_short | Changes in plasma alpha‐1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation |
| title_sort | changes in plasma alpha 1 acid glycoprotein following hemorrhagic trauma possible role in dose differences of alm drug therapy in rat and pig resuscitation |
| topic | ALM alpha‐1 acid glycoprotein dosage hemorrhage serum proteins trauma |
| url | https://doi.org/10.1002/prp2.1133 |
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