Effect of nitric oxide synthase inhibition in experimental Pseudomonas

Abstract

Purpose. The aim of this study was to assess the efficacy of the nitric oxide synthase inhibitor L-NG-nitro-arginine-methyleser (L-NAME) in the treatment of experimental Pseudomonas keratitis.

Methods. Twelve young New Zealand white rabbits were given intrastromal injections of Pseudomonas aeruginosa strains. Twenty-four hours later, the rabbits were randomly divided into four groups: group I was treated with topical 0.3% ciprofloxacin drops and a single subconjunctival injection of L-NAME (150 mg/kg); group 2 received topical 0.3% ciprofloxacin drops alone; group 3 received a single subconjunctival injection of L-NAME alone; group 4, the control group, was treated with topical balanced salt solution (BSS) drops. One drop of either ciprofloxacin of BSS was applied at each treatment interval. Twenty-six hours after the start of treatment, the eyes were examined by slit lamp to assess inflammation. Aqueous humor specimens were collected from each eye to measure the nitric oxide concentration. Corneas were removed to count bacteria results.

Results. Slit lamp examination cell scores were significantly lower for groups 1 and 3 than groups 2 and 4 eyes (p = 0.002 to p = 0.004). No Viable bacteria were detected in the corneas of groups 1 and 2. Group 3 corneas had significantly fewer bacteria (6.33 +/- 0.42 x 10(3)) than group 4 (5.94 +/- 0.16 x 10(4)) (p < 0.05). Nitric oxide levels in the aqueous humor were significantly lower for group I eyes than for groups 2, 3, or 4 (p = 0.02, p = 0.01, and p = 0.003, respectively).

Conclusions. We conclude that nitric oxide synthase inhibitors may be a useful adjunct but are not a replacement for traditional antibiotic drop therapy.