Mariana Vigiola Cruz1, Bonnie C Carney2, Jenna N Luker2, Kyle W Monger2, Juan Sebastian Vazquez3, Lauren T Moffatt3, Laura S Johnson4, Jeffrey W Shupp5. 1. Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, DC; Department of Surgery, MedStar Georgetown University Hospital, Washington, DC. 2. Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC. 3. Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, DC. 4. The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, DC. 5. Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, DC. Electronic address: Jeffrey.W.Shupp@medstar.net.
Abstract
BACKGROUND: A complex inflammatory response mediates the systemic effects of burn shock. Disruption of the endothelial glycocalyx causes shedding of structural glycoproteins, primarily syndecan-1 (SDC-1), leading to endothelial dysfunction. These effects may be mitigated by resuscitative interventions. MATERIALS AND METHODS: Sprague-Dawley rats were used to create small, medium, and large burns and uninjured controls. Three different intravenous resuscitation protocols were applied within each group: Lactated Ringer's (LR) alone, LR plus fresh frozen plasma (FFP), or LR plus albumin. Blood was serially collected, and plasma SDC-1 was quantified with enzyme-linked immunosorbent assay. In one cohort, Evan's Blue Dye (EBD) was administered and quantified in lung by spectrophotometry as a functional assay of vascular permeability. In a second cohort, intact SCD-1 was quantified by immunohistochemistry in lung tissue. Statistical analysis employed two-way analysis of variance with multiple comparisons and Student's t-test. RESULTS: EBD extraction from lung was significantly greater with higher injury severity versus controls. Extraction decreased significantly in large-burn animals with addition of FFP to LR versus LR-only; addition of albumin to LR did not decrease EBD extraction. Plasma SCD-1 increased in injured animals compared with controls, and changes correlated with injury severity in all resuscitation groups (significance, P < 0.05). Lung SCD-1 staining reflected the results in the EBD assay. CONCLUSIONS: Addition of FFP, not of albumin, to post-burn resuscitation diminishes vascular leakage associated with large burns. Addition of colloid does not affect SDC-1 shedding as measured in plasma. Ongoing work will further define pathophysiologic mechanisms and potential therapeutic interventions to mitigate injury and promote repair of the endothelial glycocalyx.
BACKGROUND: A complex inflammatory response mediates the systemic effects of burn shock. Disruption of the endothelial glycocalyx causes shedding of structural glycoproteins, primarily syndecan-1 (SDC-1), leading to endothelial dysfunction. These effects may be mitigated by resuscitative interventions. MATERIALS AND METHODS:Sprague-Dawley rats were used to create small, medium, and large burns and uninjured controls. Three different intravenous resuscitation protocols were applied within each group: Lactated Ringer's (LR) alone, LR plus fresh frozen plasma (FFP), or LR plus albumin. Blood was serially collected, and plasma SDC-1 was quantified with enzyme-linked immunosorbent assay. In one cohort, Evan's Blue Dye (EBD) was administered and quantified in lung by spectrophotometry as a functional assay of vascular permeability. In a second cohort, intact SCD-1 was quantified by immunohistochemistry in lung tissue. Statistical analysis employed two-way analysis of variance with multiple comparisons and Student's t-test. RESULTS: EBD extraction from lung was significantly greater with higher injury severity versus controls. Extraction decreased significantly in large-burn animals with addition of FFP to LR versus LR-only; addition of albumin to LR did not decrease EBD extraction. Plasma SCD-1 increased in injured animals compared with controls, and changes correlated with injury severity in all resuscitation groups (significance, P < 0.05). Lung SCD-1 staining reflected the results in the EBD assay. CONCLUSIONS: Addition of FFP, not of albumin, to post-burn resuscitation diminishes vascular leakage associated with large burns. Addition of colloid does not affect SDC-1 shedding as measured in plasma. Ongoing work will further define pathophysiologic mechanisms and potential therapeutic interventions to mitigate injury and promote repair of the endothelial glycocalyx.
Authors: David M Burmeister; Tiffany C Heard; Tony Chao; Karl Alcover; Amanda Wagner; Kevin K Chung; Kevin S Akers Journal: Crit Care Explor Date: 2022-01-05
Authors: Junru Wu; Hamed Moheimani; Shimena Li; Upendra K Kar; Jillian Bonaroti; Richard S Miller; Brian J Daley; Brian G Harbrecht; Jeffrey A Claridge; Danielle S Gruen; Herbert A Phelan; Francis X Guyette; Matthew D Neal; Jishnu Das; Jason L Sperry; Timothy R Billiar Journal: Ann Surg Date: 2022-07-19 Impact factor: 13.787
Authors: John W Keyloun; Tuan D Le; Anthony E Pusateri; Robert L Ball; Bonnie C Carney; Thomas Orfeo; Kathleen E Brummel-Ziedins; Maria C Bravo; Melissa M McLawhorn; Lauren T Moffatt; Jeffrey W Shupp Journal: Shock Date: 2021-08-01 Impact factor: 3.533
Authors: Balamurugan Packialakshmi; Ian J Stewart; David M Burmeister; Kevin K Chung; Xiaoming Zhou Journal: Ren Fail Date: 2020-11 Impact factor: 2.606