Influence of diltiazem on the ocular irritative response to nitrogen mustard

Application of nitrogen mustard to the eye of rabbits causes an anterior segment irritation and a biphasic elevation of intraocular pressure. This intraocular pressure response is composed of an initial peak, produced by neuropeptides released by excited sensory nerves, and a second, slower rise due to prostaglandins. We studied the effect of diltiazem, 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 pneumatonometry; pupil diameter and palpebral opening were measured with a ruler while conjunctival vasodilation, edema and secretion were scored in subjective units (0-8). Aqueous humor protein content was analysed at the end of the experiment. Bilateral application of 1% nitrogen mustard evoked within the first 6 hr an intraocular pressure elevation followed by ocular hypotony, miosis, palpebral closure, conjunctival vasodilation, 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 reduced significantly the acute intraocular pressure elevation and conjunctival vasodilation evoked by the irritant; delayed conjunctival edema and palpebral closure were also attenuated by 10 mM diltiazem. The decrease of miotic response and of aqueous humor protein content was not significant. Diltiazem at 2.8 mM was effective only in reducing significantly conjunctival edema and vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)