Adenosine, lidocaine, and Mg2+ (ALM) resuscitation fluid protects against experimental traumatic brain injury

Letson, Hayley L.;Dobson, Geoffrey P.

Abstract

Background: Currently, no drug therapy prevents secondary injury progression after traumatic brain injury (TBI). Our aim was to investigate the effects of small-volume intravenous adenosine, lidocaine, and Mg (ALM) resuscitation fluid after moderate TBI in a rat fluid-percussion injury model. Methods: Anesthetized, mechanically ventilated male Sprague-Dawley rats (449 ± 5 g) were randomly assigned to one of four groups: (1) sham (craniotomy without TBI), (2) no-treatment, (3) saline-control, or (4) ALM therapy groups (all n = 16). A subdural probe was implanted in eight animals per group to measure cerebral blood flow. Fifteen minutes after moderate TBI was induced with lateral fluid percussion injury (2.57 atm), a single 3% NaCl ± ALM bolus (0.7 mL/kg) was injected intravenously, and after 60 minutes (Phase 1), 0.9% NaCl ± ALM stabilization "drip" (0.5 mL/kg per hour) was administered for 3 hours (Phase 2). Results: Mortality (without subdural brain probe) was 25% (saline controls) and 0% (ALM). Sixty minutes after bolus, ALM significantly increased cardiac function, cortical blood flow (CBF; approximately threefold) and blunted systemic inflammation compared to saline controls. Three hours after infusion drip, ALM improved left ventricular function, supported higher CBF, decreased proinflammatory cytokines systemically (IL-1β, tumor necrosis factor α, and regulated on activation, normal T cell expressed and secreted [RANTES]), increased anti-inflammatory cytokines in brain tissue (IL-10, IL-4), lowered brain injury markers (neuron-specific enolase, Syndecan-1, HMGB-1), reduced coagulopathy, increased platelet aggregation, and maintained baseline fibrinogen levels. Saline-controls were proinflammatory (brain, heart, lung, and blood) and hypocoagulable with neurogenic enlargement of the right side of the heart. Survival time significantly correlated with plasma neuron-specific enolase (p = 0.001) and CBF at 180 minutes (p = 0.009), and CBF correlated with brain anti-inflammatory cytokines (p = 0.001-0.034). Conclusion: After moderate TBI, ALM resuscitation fluid increased survival and protected against early secondary injury by reducing coagulopathy, inflammation, and platelet dysfunction.

Journal

Journal of Trauma and Acute Care Surgery

Publication Name

N/A

Volume

ISBN/ISSN

2163-0763

Edition

N/A

Issue

Pages Count

Location

N/A

Publisher

Lippincott, Williams & Wilkins

Publisher Url

N/A

Publisher Location

N/A

Publish Date

N/A

Url

N/A

Date

N/A

EISSN

N/A

DOI

10.1097/TA.0000000000001874