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

Fernando Dos Santos, Joyce B Li, Nathalia Jd Moreira, Rafi Mazor, Federico Aletti, Erik B Kistler

Open access · greenAbstract read

In one paragraph

Article in American journal of translational research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it

0cells of the map it votes in

2citing papers in PubMed

0.5field-weighted citation impact, top 37% of its field

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 3 citations in OpenAlex.

Arterial compliance is improved via enteral serine protease inhibition in experimental trauma/hemorrhagic shock.Frontiers in physiology · 2025
Article
Enteral administration of the protease inhibitor gabexate mesilate preserves vascular function in experimental trauma/hemorrhagic shock.Scientific reports · 2023
Article

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Fernando Dos SantosDepartment of Anesthesiology & Critical Care, University of California San Diego, La Jolla, CA, USA.

Joyce B LiDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.

Nathalia Jd MoreiraInstituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo São Paulo, Brazil.

Rafi MazorDepartment of Anesthesiology & Critical Care, University of California San Diego, La Jolla, CA, USA.

Federico AlettiDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.

Erik B KistlerDepartment of Anesthesiology & Critical Care, University of California San Diego, La Jolla, CA, USA.

University of California, San Diego · USVA San Diego Healthcare System · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 post-pyloric for the infusion of vehicle (Golytely®) 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 α1-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 α1 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.

Indexed as

autonomic cardiovascular functionenteral protease inhibitiongabexate mesilateTrauma/hemorrhagic shock

Identifiers

PMID36398214

PMCPMC9641450

OpenAlexW4309410410

What OpenQuestion holds

Textmetadata

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.