INHALED NITRIC OXIDE REDUCES LUNG INFLAMMATION IN RATS EXPOSED TO 100% OXYGEN. † 271

Abstract

Patients with pulmonary hypertension are now commonly being treated with inhaled nitric oxide (NO) along with high concentrations of oxygen. High concentrations of supplemental oxygen can clearly lead to lung injury, and the effect of inhaled NO on the course of hyperoxic lung injury is uncertain. Hyperoxia-induced lung damage is associated with inflammation, and number of neutrophils in the lung has been correlated with magnitude of injury. Neutrophil accumulation in other tissues has been shown to be decreased by nitric oxide NO precursors, and increased by NO synthase inhibitors. We therefore hypothesized that NO would decrease the inflammatory response to hyperoxia in rat lungs. Lung tissue was obtained at 24 and 48 hours from adult Sprague-Dawley rats exposed to either >95% oxygen alone, or from rats exposed to >95% oxygen with 100 parts per million of inhaled NO (INO). Lung samples were also taken from air-breathing rats and used as controls. To identify inflammatory cells, lung sections were stained immunohistochemically for myeloperoxidase. After 24 hours of hyperoxia-exposure there was interstitial edema noted in both groups with an accumulation of mixed inflammatory cells (neutrophils and macrophages) in the lung interstitium and perivascular areas of lungs exposed to hyperoxia alone. After 48 hours of hyperoxia-exposure there was increased pulmonary edema evident in both groups, whereas in the hyperoxia alone group there was a dramatic increase in inflammatory cells in the lung interstitium relative to the earlier hyperoxia-exposure times and to the hyperoxia + INO animals at 48 h. There were no differences in alveolar inflammatory cell accumulations noted in hyperoxia alone and hyperoxia + INO groups. In conclusion, INO appeared to reduce the lung inflammatory response to hyperoxia, and suggests that INO may exert a beneficial response by its effects on lung inflammation.