Bradykinin release following trauma and hemorrhagic shock causes pulmonary alveolar leak in a rodent model.
J Trauma Acute Care Surg
; 95(4): 558-564, 2023 10 01.
Article
em En
| MEDLINE
| ID: mdl-37314576
ABSTRACT
BACKGROUND:
Hemorrhage accounts for 40% of the preventable death following severe injury. Activation of systemic coagulation produces bradykinin (BK), which may cause leak from the plasma to the extravascular space and to the tissues, which is part of the complex pathophysiology of trauma-induced end-organ injury. We hypothesize that BK, released during activation of coagulation in severe injury, induces pulmonary alveolar leak.METHODS:
Isolated neutrophils (PMNs) were pretreated with a specific BK receptor B2 antagonist HOE-140/icatibant and BK priming of the PMN oxidase was completed. Rats underwent tissue injury/hemorrhagic shock (TI/HS), TI/icatibant/HS, and controls (no injury). Evans blue dye was instilled, and the percentage leak from the plasma to the lung was calculated from the bronchoalveolar lavage fluid (BALF). CINC-1 and total protein were measured in the BALF, and myeloperoxidase was quantified in lung tissue.RESULTS:
The BK receptor B2 antagonist HOE140/icatibant inhibited (85.0 ± 5.3%) BK priming of the PMN oxidase ( p < 0.05). The TI/HS model caused activation of coagulation by increasing plasma thrombin-antithrombin complexes ( p < 0.05). Versus controls, the TI/HS rats had significant pulmonary alveolar leak 1.46 ± 0.21% versus 0.36 ± 0.10% ( p = 0.001) and increased total protein and CINC-1 in the BALF ( p < 0.05). Icatibant given after the TI significantly inhibited lung leak and the increase in CINC-1 in the BALF from TI/icatibant/HS rats versus TI/HS ( p < 0.002 and p < 0.05) but not the total protein. There was no PMN sequestration in the lungs.Conclusions:
This mixed injury model caused systemic activation of hemostasis and pulmonary alveolar leak likely due to BK release.CONCLUSION:
This mixed injury model caused systemic activation of hemostasis and pulmonary alveolar leak likely due to BK release. LEVEL OF EVIDENCE Original Article, Basic Science.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Choque Hemorrágico
/
Bradicinina
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article