Abstract
BACKGROUND Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. CONCLUSION P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 583-590 |
| Number of pages | 8 |
| Journal | Journal of Trauma and Acute Care Surgery |
| Volume | 86 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2019 |
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Keywords
- blunt thoracic trauma
- clot
- P-selectin
- pulmonary embolism
- thrombosis
ASJC Scopus subject areas
- Surgery
- Critical Care and Intensive Care Medicine
Cite this
P-Selectin Is Critical for de Novo Pulmonary Arterial Thrombosis Following Blunt Thoracic Trauma. / Schutzman, Linda M.; Rigor, Robert R.; Khosravi, Nasim; Galante, Joseph M; Brown, Ian Elliott.
In: Journal of Trauma and Acute Care Surgery, Vol. 86, No. 4, 01.04.2019, p. 583-590.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - P-Selectin Is Critical for de Novo Pulmonary Arterial Thrombosis Following Blunt Thoracic Trauma
AU - Schutzman, Linda M.
AU - Rigor, Robert R.
AU - Khosravi, Nasim
AU - Galante, Joseph M
AU - Brown, Ian Elliott
PY - 2019/4/1
Y1 - 2019/4/1
N2 - BACKGROUND Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. CONCLUSION P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.
AB - BACKGROUND Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. CONCLUSION P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.
KW - blunt thoracic trauma
KW - clot
KW - P-selectin
KW - pulmonary embolism
KW - thrombosis
UR - http://www.scopus.com/inward/record.url?scp=85063712369&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063712369&partnerID=8YFLogxK
U2 - 10.1097/TA.0000000000002166
DO - 10.1097/TA.0000000000002166
M3 - Article
C2 - 30562326
AN - SCOPUS:85063712369
VL - 86
SP - 583
EP - 590
JO - Journal of Trauma and Acute Care Surgery
JF - Journal of Trauma and Acute Care Surgery
SN - 2163-0755
IS - 4
ER -