Severe Trauma and Hemorrhage Leads to Platelet Dysfunction and Changes in Cyclic Nucleotides in the Rat

Daniel N. Darlington, Xiaowu Wu, Jeffrey D. Keesee, Andrew P. Cap

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Introduction:Rats subjected to polytrauma and hemorrhage develop a coagulopathy that is similar to acute coagulopathy of trauma in humans, and is associated with a rise in prothrombin time and a fall in clot strength. Because platelet aggregation accounts for a major proportion of clot strength, we set out to characterize the effects of polytrauma on platelet function.Methods:Sprague-Dawley rats were anesthetized with isoflurane. Polytrauma included laparotomy and damage to 10cm of the small intestines, right and medial liver lobes, right leg skeletal muscle, femur fracture, and hemorrhage (40% of blood volume). No resuscitation was given. Blood samples were taken before and after trauma for the measurement of impedance electrode aggregometry, and intracellular levels of cyclic adenosine and guanosine monophosphate (cAMP, cGMP), inositol trisphosphate (IP3), and adenosine and guanosine triphosphates (ATP, GTP).Results:Polytrauma significantly increased the response of collagen (24%) and thrombin (12%) to stimulate platelet aggregation. However, aggregation to adenosine diphosphate (ADP) or arachidonic acid (AA) was significantly decreased at 2 (52% and 46%, respectively) and 4 h (45% and 39%). Polytrauma and hemorrhage also led to a significant early rise in cAMP (101±11 to 202±29pg/mL per 1,000 platelets), mirrored by a decrease in cGMP (7.8±0.9 to 0.6±0.5). In addition, there was a late fall in ATP (8.1±0.7 to 2.2±0.6 ng/mL per 1,000 platelets) and GTP (1.5±0.2 to 0.3±0.1). IP3 rose initially, and then fell back to baseline.Conclusions:Polytrauma and hemorrhage led to a deficit in the platelet aggregation response to ADP and AA after trauma, likely due to the early rise in cAMP, and a later fall in energy substrates, and may explain the decrease in clot strength and impaired hemostasis observed after severe trauma.

Original languageEnglish (US)
Pages (from-to)468-475
Number of pages8
JournalShock
Volume53
Issue number4
DOIs
StatePublished - Apr 1 2020

Keywords

  • ATP
  • Adenylate cyclase
  • GTP
  • IP3
  • aggregation
  • cAMP
  • cGMP

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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