Corneal toxicity of xylazine and clonidine, in combination with ketamine, in the rat

Purpose: To compare the corneal toxicity of xylazine (XYL)/ketamine (KET) with that of clonidine (CLO)/KET in the rat, in the presence or not of the α2-adrenergic antagonist yohimbine (YOH). Methods: XYL (10 mg/kg) and CLO (0.15 mg/kg) were administered subcutaneously in the rat in combination with KET (50 mg/kg), in the presence or not of YOH (2 mg/kg). Results: The corneas immediately lost transparency and luster, but recovered within 120 min. By both light and electron microscopy, a marked stromal edema and alterations of all layers were observed. In addition, XYL/KET altered the permeability of the cornea as indicated by the augmented levels of 14C-indomethacin, topically administered 30 min after the anesthetic combination. Conclusions: The mechanism of the corneal toxicity of XYL and CLO in the rat is unclear but we speculate that: (a) proptosis and inhibition of normal blinking did not play a major role because topical application of hyaluronic acid did not protect against it; corneal decompensation, edema and opacification could be due to (b) osmotic or (c) mechanical endothelial stress: the first resulting from the sudden increase of the glucose concentration in the aqueous humor due to the well-known inhibition of insulin release by α2-adrenergic agonists, and the second from the acute elevation of intraocular pressure caused by these α2-adrenergic mydriatics in the rat; (d) addition, XYL and CLO could act by directly interacting with local α2- or, possibly, α1-adrenergic receptors, whose function is still not clear but probably essential for corneal homeostasis.