Le glycoalyx: Une cible thérapeutique

Novel Adjunct Drugs Reverse Endothelial Glycocalyx Damage After Hemorrhagic Shock in Rats.

 

Torres Filho IP et Al. Shock. 2017 Nov;48(5):583-589

 

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La correction précoce de la coagulopathie traumatique est un des objectifs fondamentaux de la prise en charge du traumatisé sévère et en particulier des blessés de guerre. L'emploi de plasma lyophilisé / fibrinogène / fractions coagulantes concentrées et la transfusion de sang frais se fait selon des stratégies diverses visant à compenser les déficits observés (1) . La restauration d'une perméabilité capillaire est également une voie possible. On peut considérer que l'efficacité du plasma est en +/- grande partie liée à sa capacité à restaurer le glycocalyx endothélial (2). Le travail présenté est en faveur de l'emploi, à l'instar de l'acide tranexaminique pour la fibrinolyse, d'ajuvants pharmacologiques aux solutés de remplissage pour limiter l'atteinte du glycoclayx.

Allez sur le forum coagulopathie/transfusion

Mieux comprende le concept de perméabilité capillaire

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INTRODUCTION:

There is interest in the small-volume therapeutic use of adjunct drugs for treating hemorrhagic shock (HS). However, critical information is only partially available on mechanisms of action of promising compounds such as adenosine-lidocaine-magnesium (ALM), beta-hydroxybutyrate plus melatonin (BHB/M), and poloxamer 188 (P-188). Therefore, we tested the hypothesis that these adjuncts would reverse HS-induced damage to microvascular endothelial glycocalyx and hemodynamics.

METHODS:

After baseline, 40% of total blood volume was removed from 44 anesthetized Sprague-Dawley male rats. One hour after hemorrhage, animals were resuscitated using ALM, BHB/M, or P-188 followed by lactated Ringer's (LR, 15 mL/kg). Control animals were not treated (SHAM) or received LR alone. Sampled blood was used to quantify shed syndecan-1 in plasma; multiple systemic physiological parameters were recorded. In vivo glycocalyx thickness, microvascular permeability, and microhemodynamics were evaluated in >200 cremaster venules using intravital videomicroscopy.

RESULTS:

Compared with baseline, resuscitation using adjuncts was associated with glycocalyx restoration of 97 ± 9% (ALM), 75 ± 8% (BHB/M), and 85 ± 5% (P-188): significantly higher than LR-only (56 ± 4%). Significantly better permeability, similar to SHAM values, was measured after ALM and P-188, and low plasma syndecan-1 levels were measured after resuscitation with all adjuncts. Microhemodynamic changes were relatively small while systemic parameters such as mean arterial pressure and lactate improved but remained below or above the baseline, respectively, as expected from this hypotensive resuscitation model.

CONCLUSION:

The drugs ALM, BHB/M, and P-188 provide beneficial effects as adjuncts to hypotensive resuscitation in this HS model by mechanisms involving changes at the microvascular level including the glycocalyx.