Inducible nitric oxide mediates systemic microvascular leak following acid aspiration and mechanical ventilation

Abstract

Background and aims: The systemic effects associated with mechanical venti- lation of lungs injured by hydrochloric acid (HCl) aspiration are unexplored. We hypothesize that low dose acid aspiration will predispose the lung and the kidney to damage from large tidal volumes through activation of inducible nitric oxide syn- thase (iNOS). Materials and methods: Hydrochloric acid (HCl; pH 1.25, 1 mL/kg ), or an equal amount of 0.9% sodium chloride (NaCl), were inserted into the tra- chea of rats immediately prior to mechanical ventilation. Rats were then ventilated with room air at 85 breaths per minute for 2 hours, either with a tidal volume (V T )of 7 mL/kg or 14 mL/kg (V T 7, V T 14) and zero end expiratory pressure. Kidney microvas- cular leak, which was assessed by measuring urine protein over 24 hours and by Evans blue dye (EBD) technique, was used as an indicator of systemic microvascu- lar leak. Results: A significant microvascular leak occurred in both lung and kidney exposed to V T 14 with HCl compared to those exposed to either V T 7withHClor the NaCl control group. iNOS activity was significantly increased in the lung and the kidney tissue in V T 14 with acid aspiration. The relatively selective iNOS inhibitor, L-N6-(1-iminoethyl)lysine (L-NIL), attenuated the EBD microvascular leak in lung and kidney and the proteinuria in the V T 14 with acid aspiration group. Conclusion: iNOS may have mediated the systemic microvascular leak in the present model.