Eight hours' inhalation of prostacyclin (PGI(2)) in healthy lambs: Effects on tracheal, bronchial, and alveolar morphology

Objective: To study potential toxic effects of long-term (8 h) inhaled prostacyclin (PGI(2)) on respiratory tract tissues. Design: In a prospective, randomized order, either PGI(2) (n = 7) or normal saline (n = 7) was aerosolized during a time period of 8 h in healthy lambs. Setting: Institute for Surgical Research of the Ludwig-Maximilians University of Munich. Animals: 14 healthy, anesthetized, ventilated lambs. Interventions: All animals were endotracheally intubated followed by tracheotomy. PGI(2) solution or normal saline was administered with a jet nebulizer (delivery rate 4-10 ml/h; mass median diameter of aerosol particles 3.1 mu m). Measurements and results: Histomorphological changes after 8-h inhalation of PGI(2) solution were compared to those after 8-h inhalation of normal saline. Tracheal and bronchoalveolar tissues were examined by light and electron microscopy in order to assess tissue damage induced by inhaled PGI(2). Pathological changes were ranked by a blinded observer following a graduation system ranging from ''absence of pathological changes'' to ''maximal pathological changes''. Abnormalities were restricted to the trachea (focal flattening of the epithelium, loss of cilia, slight inflammatory cell infiltration) and alveolar tissue (focal alveolar septal thickening with slight inflammatory cell infiltration), but no statistically significant differences between the PGI(2) and control groups were encountered, Conclusion: Our findings indicate the absence of PGI(2) aerosol-related respiratory tissue damage after 8-h inhalation of PGI(2).