Vatinoxan Prevents Medetomidine-Associated Exophthalmos and Increased Glucose Concentrations in Blood and Aqueous Humor in Rats

Purpose: To evaluate whether vatinoxan, a peripherally selective alpha 2 -adrenoceptor antagonist, prevents the acute, medetomidine-associated ophthalmic changes in rats. Methods: Adult male Wistar rats ( n = 9 in each group) were randomly allocated to receive subcutaneous medetomidine 0.4 mg/kg and midazolam 2 mg/kg (MM), MM with vatinoxan 8 mg/kg (MM-V), or MM with regular insulin 1 IU/kg (MM-I). Macroscopic photography (to assess globe position) and slit-lamp biomicroscopy were performed, and blood glucose (BG) concentration, intraocular pressure (IOP), and central corneal thickness (CCT) were measured at intervals until 50 min post-treatment. Surgical anesthesia was then induced, and aqueous humor glucose (AHG) concentration was measured prior to euthanasia. Results: In MM and MM-I, exophthalmos worsened over time ( P < 0.05) and compared to MM-V ( P ≤ 0.04 for both). BG increased significantly over time ( P < 0.001) only in MM, and AHG was significantly higher in MM than in MM-V and MM-I ( P < 0.001). Lens clarity was decreased at 50 min in both MM ( P = 0.002) and MM-I ( P = 0.048), compared to MM-V. CCT was greater in MM-V than in MM at 50 min ( P = 0.02). Corneal clarity remained unchanged. IOP declined in all groups but remained significantly higher in MM-V 10 min versus 50 min post-treatment ( P = 0.02). Conclusions: Vatinoxan prevented pathological exophthalmos, lens opacification, the acute decline in IOP, hyperglycemia, and increased AHG in rats sedated with medetomidine–midazolam. Insulin similarly prevented hyperglycemia, but none of the ophthalmic changes. Acute alpha 2 -adrenoceptor agonist-mediated ophthalmic pathologies are independent from glycemic control.