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

Purpose: To compare the corneal toxicity of xylazine (XYL)/ketamine (KET) w ith that of clonidine (CLO)/KET in the rat, in the presence or not of the a lpha (2)-adrenergic antagonist yohimbine (YOH). Methods: XYL (10 mg/kg) and CLO (0.15 mg/kg) were administered subcutaneously in the rat in combinatio n with KET (50 mg/kg), in the presence or not of YOH (2 mg/kg). Results: Th e corneas immediately lost transparency and luster, but recovered within 12 0 min. By both light and electron microscopy, a marked stromal edema and al terations of all layers were observed. In addition, XYL/KET altered the per meability of the cornea as indicated by the augmented levels of C-14-indome thacin, topically administered 30 min after the anesthetic combination. Con clusions: The mechanism of the corneal toxicity of XYL and CLO in the rat i s unclear but we speculate that: (a) proptosis and inhibition of normal bli nking did not play a major role because topical application of hyaluronic a cid did not protect against it; corneal decompensation, edema and opacifica tion could be due to (b) osmotic or (c) mechanical endothelial stress: the first resulting from the sudden increase of the glucose concentration in th e aqueous humor due to the well-known inhibition of insulin release by alph a (2)-adrenergic agonists, and the second from the acute elevation of intra ocular pressure caused by these alpha (2)-adrenergic mydriatics in the rat; (d) addition, XYL and CLO could act by directly interacting with local alp ha (2)- or, possibly, alpha (1)-adrenergic receptors, whose function is sti ll not clear but probably essential for corneal homeostasis. Copyright (C) 2001 S. Karger AG, Basel.