Remimazolam improves survival and attenuates glycocalyx-related injury after hemorrhagic shock in rats.

Abstract

Systemic inflammatory activation and endothelial glycocalyx injury contribute to organ dysfunction and poor outcomes after hemorrhagic shock. We investigated whether remimazolam improved survival and attenuated inflammatory activation and glycocalyx-related injury in a rat model of hemorrhagic shock and explored whether these effects were sensitive to flumazenil. Ninety male Sprague-Dawley rats underwent hemorrhagic shock by reducing mean arterial pressure to 40-45 mmHg for 60 minutes, followed by fluid resuscitation. Animals were assigned to five groups: normal saline (Control-S), low-dose remimazolam (LowR, 5 mg/kg), high-dose remimazolam (HighR, 10 mg/kg), high-dose remimazolam with flumazenil (Control-F), and flumazenil alone (Flu). Survival time, serum tumor necrosis factor-α, serum syndecan-1, myocardial glycocalyx thickness, and coverage ratio were evaluated. Survival time differed significantly among the five groups (overall log-rank P=0.00025). Remimazolam was associated with lower serum tumor necrosis factor-α and syndecan-1 levels than those in the control groups. Animal-level TEM analysis showed significant overall group differences in endothelial glycocalyx thickness and coverage ratio, although no adjusted pairwise comparisons reached statistical significance. Remimazolam administration was associated with improved survival, lower tumor necrosis factor-α levels, reduced circulating glycocalyx shedding, and a pattern suggestive of partial structural glycocalyx preservation in this rat model of hemorrhagic shock. Flumazenil co-administration attenuated several remimazolam-associated findings; however, a specific mechanism was not established.