Enteral gabexate mesilate improves volume requirements and autonomic cardiovascular function after experimental trauma/hemorrhagic shock in the absence of blood reperfusion

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art_SANTOS_Enteral_gabexate_mesilate_improves_volume_requirements_and_autonomic_2022.PDF (1.63 MB)
Citações na Scopus
Tipo de produção
article
Data de publicação
2022
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
E-CENTURY PUBLISHING CORP
Autores
SANTOS, Fernando Dos
LI, Joyce B.
MAZOR, Rafi
ALETTI, Federico
KISTLER, Erik B.
Citação
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH, v.14, n.10, p.7391-+, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The standard of care for fluid resuscitation of trauma/hemorrhagic shock (T/HS) is the infusion of blood. However, in many instances, blood product transfusion may not be feasible. Consequently, crystalloid solutions may be utilized as temporizing cost-effective resuscitation fluids. In this study, we explored an alternative therapeutic strategy of enteral protease inhibition adjunctive to intravenous Lactated Ringer's (LR) reperfusion after T/HS. Male Wistar rats underwent midline laparotomy (trauma) and an enteral catheter was inserted orally and positioned postpyloric for the infusion of vehicle (Golytely (R)) with or without the serine protease inhibitor gabexate mesilate (GM) (n=8/group). Hemorrhagic shock was induced by blood removal to reduce the mean arterial blood pressure (MAP) to 35-40 mmHg for 90 minutes, before resuscitation with LR. Animals treated with enteral GM required significantly less crystalloid volume to achieve hemodynamic stability and displayed improvements in both blood pressure and autonomic function (via increased baroreflex sensitivity to vasopressors, heightened vascular sympathetic modulation, elevated levels of circulating catecholamines, and increased alpha 1-adrenergic receptor density) compared to untreated (control) shocked animals. Resistance arteries isolated from healthy donor animals and perfused with plasma from untreated T/HS animals revealed impaired vascular response to the alpha 1 adrenergic agonist phenylephrine and decreased reactivity to sodium nitroprusside that was preserved in the GM-treated group. These findings suggest that blockade of serine proteases within the intestinal lumen in non-blood resuscitated experimental T/HS preserves and enhances peripheral sympathetic modulation, improving hemodynamics. Enteral infusion of gabexate mesilate may be a new and promising approach to the management of trauma/hemorrhagic shock.
Palavras-chave
Trauma/hemorrhagic shock, enteral protease inhibition, gabexate mesilate, autonomic cardiovascular function
URI
https://observatorio.fm.usp.br/handle/OPI/50700
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - LIM/59