INFLUENCE OF DILTIAZEM ON THE OCULAR IRRITATIVE RESPONSE TO NITROGEN-MUSTARD

Application of nitrogen mustard to the eye of rabbits causes an anteri or segment irritation and a biphasic elevation of intraocular pressure . This intraocular pressure response is composed of an initial peak, p roduced by neuropeptides released by excited sensory nerves, and a sec ond, slower rise due to prostaglandins. We studied the effect of dilti azem, a calcium antagonist that selectively blocks chemical excitation of sensory nerves, on the inflammatory response to nitrogen mustard. In adult rabbits, intraocular pressure was determined by pneumatonomet ry; pupil diameter and palpebral opening were measured with a ruler wh ile conjunctival vasodilation, edema and secretion were scored in subj ective units (0-8). Aqueous humor protein content was analysed at the end of the experiment. Bilateral application of 1% nitrogen mustard ev oked within the first 6 hr an intraocular pressure elevation followed by ocular hypotony, miosis, palpebral closure, conjunctival vasodilati on, edema and an elevation of aqueous proteins. Topical application of 10 mM diltiazem, prior to administration of nitrogen mustard elicited by itself a transient, small intraocular pressure increase and reduce d significantly the acute intraocular pressure elevation and conjuncti val vasodilation evoked by the irritant; delayed conjunctival edema an d palpebral closure were also attenuated by 10 mM diltiazem, The decre ase of miotic response and of aqueous humor protein content was not si gnificant. Diltiazem at 2.8 mM was effective only in reducing signific antly conjunctival edema and vasodilation. Intravenous injection of di ltiazem (1 mg kg(-1)) elicited a gradual intraocular pressure drop las ting 1-2 hr and failed to attenuate ocular inflammatory signs when app lied prior to topical nitrogen mustard, except for the initial intraoc ular pressure rise, that was partially counteracted by the IOP drop in duced by i.v. diltiazem. The results indicate that topical diltiazem a t 10 mM concentration reduced chemical irritation of the eye evoked by nitrogen mustard. This effect appears to be due in part to a blockade of the initial neurogenic component of the irritative reaction to nit rogen mustard and in part to a direct action of the drug on cells cont ributing to the local inflammatory response. (C) 1995 Academic Press L imited