Etomidate decreases adrenal gland apoptosis and necrosis associated with hemorrhagic shock in a rat model (Rattus norvegicus)

Abstract

Abstract Purpose: Evaluate if etomidate modulates adrenal apoptosis and if this influences the development of critical illness-related corticosteroid insufficiency (CIRCI) in hemorrhagic shock (HS). Material and methods: Four groups of 16 male Wistar rats: G0 (control group anesthetized with isoflurane and mechanical ventilation), G1 (like G0, but with buprenorphine), G2 (like G1 with HS), and G3 (like G2 with etomidate 1 mg/kg, IV, before HS). HS induced by collecting 30% of blood volume. Resuscitation performed 90 min later with the collected blood and normal saline. Hemodynamic parameters, blood gas analysis, adrenocorticotropic hormone (ACTH), corticosterone (CS), and TNF-α, IL6, IL10 were determined at 0, 90, 150, and 240 min post-HS induction (at the corresponding time points in G0 and G1). Apoptosis and necrosis were determined by TUNEL and caspase-3 immunofluorescence and a necrosis score, respectively. Results: HS groups had significantly higher levels of apoptosis and necrosis than G1 and G0. Compared with G2, etomidate-treated animals had significantly lower levels of CS (compatible with CIRCI), PO2, PO2/FiO2, BE, HCO3, apoptosis, and necrosis and significantly higher cytokine levels. Conclusions: Etomidate was associated with CIRCI. HS was associated with adrenal gland apoptosis and necrosis. The latter were decreased by etomidate, possibly by both direct and indirect mechanisms.