Robert P Richter1, Robert T Russell2, Parker J Hu3, Rindi M Uhlich4, Thomas A Swain5, Jeffrey D Kerby3, Jean-Francois Pittet6, Jillian R Richter3. 1. Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama. 2. Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama. 3. Division of Trauma and Acute Care Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama. 4. Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama. 5. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama. 6. Division of Critical Care Anesthesiology, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Abstract
BACKGROUND: Angiopoietin-1 (Agpt-1) and Agpt-2 are cytokine regulators of vascular endothelial integrity. Elevated plasma Agpt-2 levels and ratios of Agpt-2:Agpt-1 are associated with adverse outcomes in adult trauma and pediatric sepsis populations. However, the behavior of the angiopoietins after pediatric trauma has not been characterized, and their relationship to endothelial glycocalyx damage, indicated by plasma syndecan-1 (Syn-1) levels, has not been established. METHODS: We performed a secondary analysis of prospectively collected data from 52 pediatric trauma patients and 12 control patients at a level one pediatric trauma center from 2013 to 2016. We measured Agpt-1, Agpt-2, and Syn-1 levels from plasma taken upon hospital arrival and 24 h after admission. Angiopoietin levels were compared to controls, and the correlation between Agpt-2 and Syn-1 was assessed. RESULTS: Plasma Agpt-1 and Agpt-2 levels are elevated immediately after pediatric trauma compared with controls. At 24 h, trauma patients demonstrated significantly elevated plasma Agpt-2:Agpt-1 ratios relative to controls due to decline of Agpt-1 levels to near that of controls. Higher 24-h Agpt-2 levels are associated with more hypoperfusion, and elevated 24-h Agpt-2:Agpt-1 ratios are associated with adverse clinical outcomes. Significant positive correlations between Agpt-2 and Syn-1 upon admission and at 24 h after injury were identified. CONCLUSION: Our findings suggest dysregulation of circulating angiopoietins after pediatric trauma that may be linked to endothelial glycocalyx injury. Larger prospective studies are needed to validate these findings and determine the relationship of Agpt-2 with other markers of endotheliopathy.
BACKGROUND:Angiopoietin-1 (Agpt-1) and Agpt-2 are cytokine regulators of vascular endothelial integrity. Elevated plasma Agpt-2 levels and ratios of Agpt-2:Agpt-1 are associated with adverse outcomes in adult trauma and pediatric sepsis populations. However, the behavior of the angiopoietins after pediatric trauma has not been characterized, and their relationship to endothelial glycocalyx damage, indicated by plasma syndecan-1 (Syn-1) levels, has not been established. METHODS: We performed a secondary analysis of prospectively collected data from 52 pediatric traumapatients and 12 control patients at a level one pediatric trauma center from 2013 to 2016. We measured Agpt-1, Agpt-2, and Syn-1 levels from plasma taken upon hospital arrival and 24 h after admission. Angiopoietin levels were compared to controls, and the correlation between Agpt-2 and Syn-1 was assessed. RESULTS: Plasma Agpt-1 and Agpt-2 levels are elevated immediately after pediatric trauma compared with controls. At 24 h, traumapatients demonstrated significantly elevated plasma Agpt-2:Agpt-1 ratios relative to controls due to decline of Agpt-1 levels to near that of controls. Higher 24-h Agpt-2 levels are associated with more hypoperfusion, and elevated 24-h Agpt-2:Agpt-1 ratios are associated with adverse clinical outcomes. Significant positive correlations between Agpt-2 and Syn-1 upon admission and at 24 h after injury were identified. CONCLUSION: Our findings suggest dysregulation of circulating angiopoietins after pediatric trauma that may be linked to endothelial glycocalyx injury. Larger prospective studies are needed to validate these findings and determine the relationship of Agpt-2 with other markers of endotheliopathy.
Authors: Sunil Rangarajan; Jillian R Richter; Robert P Richter; Shyam K Bandari; Kaushlendra Tripathi; Israel Vlodavsky; Ralph D Sanderson Journal: J Histochem Cytochem Date: 2020-07-06 Impact factor: 2.479
Authors: Robert P Richter; Danielle M Joiner; Russell L Griffin; Jan O Jansen; Jeffrey D Kerby; Charles E Wade; John B Holcomb; Jessica C Cardenas; Jillian R Richter Journal: Ann Surg Open Date: 2022-03
Authors: Anoek L I van Leeuwen; Nicole A M Dekker; Paul Van Slyke; Esther de Groot; Marc G Vervloet; Joris J T H Roelofs; Matijs van Meurs; Charissa E van den Brom Journal: Intensive Care Med Exp Date: 2021-05-17
Authors: Robert P Richter; Amit R Ashtekar; Lei Zheng; Danielle Pretorius; Tripathi Kaushlendra; Ralph D Sanderson; Amit Gaggar; Jillian R Richter Journal: JCI Insight Date: 2022-08-08
Authors: Delphine Borgel; Richard Chocron; Marion Grimaud; Aurélien Philippe; Judith Chareyre; Charlyne Brakta; Dominique Lasne; Damien Bonnet; Julie Toubiana; François Angoulvant; Maximilien Desvages; Sylvain Renolleau; David M Smadja; Mehdi Oualha Journal: Crit Care Med Date: 2021-11-01 Impact factor: 9.296