8 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 pros pective, randomized order, either PGI(2) (n = 7) or normal saline (n = 7) was aerosolized during a time period of 8 h in healthy lambs. Sett ing: Institute for Surgical Research of the Ludwig-Maximilians Univers ity of Munich. Animals: 14 healthy, anesthetized, ventilated lambs. In terventions: All animals were endotracheally intubated followed by tra cheotomy. PGI(2) solution or normal saline was administered with a jet nebulizer (delivery rate 4-10 ml/h; mass median diameter of aerosol p articles 3.1 mu m). Measurements and results: Histomorphological chang es after 8-h inhalation of PGI(2) solution were compared to those afte r 8-h inhalation of normal saline. Tracheal and bronchoalveolar tissue s were examined by light and electron microscopy in order to assess ti ssue damage induced by inhaled PGI(2). Pathological changes were ranke d by a blinded observer following a graduation system ranging from ''a bsence 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 inflamma tory cell infiltration), but no statistically significant differences between the PGI(2) and control groups were encountered, Conclusion: Ou r findings indicate the absence of PGI(2) aerosol-related respiratory tissue damage after 8-h inhalation of PGI(2).