Amelioration of Ischemia–Reperfusion Injury in an Isolated Rabbit Lung Model Using OXANOH

Abstract

Objective: Acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality. Oxygen-free radicals (OFRs) produced during ischemia and reperfusion (IR) have been implicated as the final common pathway in the pathogenesis of this syndrome. Spin traps have been shown to decrease IR injury in several animal lung models. The hydroxylamine, OXANOH (2-ethyl-2,5,5-trimethyl-3-oxazolidine) has been proposed as an ideal spin trap that would trap extra- and intracellular OFRs producing the stable radical, OXANO^• (2-ethyl-2,5,5-trimethyl-3-oxazolidinoxyl). Electron microscopy was used to investigate whether OXANOH would protect against IR injury in the rabbit lung. Methods: OXANOH was obtained by hydrogenation of its stable radical, OXANO^• using a safe laboratory technique. Several doses of OXANOH were tested to identify a nontoxic dose. Two quantitative methods were used based on the average surface area of the alveoli and average number of alveoli per unit surface area using scanning electron microscopy (SEM). A total of 20 animals were subjected to 2 hours of ischemia followed by 4 hours of reperfusion. On reperfusion, the 4 groups (N = 5) received no treatment, OXANOH, superoxide dismutase (SOD)/catalase, or oxypurinol. Results: A therapeutic dose of 250 μmol/L of OXANO^• was suggested in this in vitro model. All the 3 treatments showed significantly less injury compared to the control group and that SOD/catalase was significantly different from OXANOH and oxypurinol (P < .008). Conclusion: OXANOH ameliorated IR injury in the isolated rabbit lung, almost as effectively as SOD/catalase and oxypurinol.