Inhalation of prostacyclin (PGI(2)) for 8 hours does not produce signs of acute pulmonary toxicity in healthy lambs

Objective: To study the potential side effects and toxicity of inhaling prostacyclin (PGI(2)) aerosol for 8 h. Design: In a prospective, randomized study 14 healthy lambs received either PGI(2) (n = 7) or 0.9% NaCl (n = 7) as an aerosol for 8 h. Setting: Institute for Surgical Research of the Ludwig-Maximilians-University of Munich. Interventions: All animals were studied under general anesthesia in a prone position. They were first intubated endotracheally and later tracheotomized. PGI(2) solution (median dose 28 ng/kg per min) or 0.9% NaCl was administered with a jet nebulizer (delivery rate 4-10 ml/h; mass median diameter of aerosol particles 3.1 mu m). Bronchoalveolar lavage was performed before and after the inhalation period to collect epithelial lining fluid of alveoli. Measurements and results: Hemodynamic and respiratory parameters, systemic resorption (plasma levels of 6-keto-prostaglandin-F1 alpha), in vitro bleeding time, collagen-induced platelet aggregation and global biochemical and cellular composition of the epithelial lining fluid were examined in order to assess the side effects and signs of acute pulmonary toxicity induced by inhaled PGI(2). No statistically significant differences were found between the PGI(2) and the control groups for any of the parameters examined. Conclusion: Inhalation of PGI, (28 ng/kg per min) over a period of 8 h in healthy lambs does not produce major side effects or acute pulmonary toxicity.