TY - JOUR T1 - Local Effects of Two Intravenous Formulations of Pulmonary Vasodilators on Airway Epithelium JF - Respiratory Care DO - 10.4187/respcare.07938 SP - respcare.07938 AU - Bradley A. Kuch AU - Rosalie Linssen AU - Hiroki Yoshikawa AU - Craig D. Smallwood AU - Michael D. Davis Y1 - 2020/06/09 UR - http://rc.rcjournal.com/content/early/2020/06/09/respcare.07938.abstract N2 - Background: Intravenous formulations of epoprostenol are frequently delivered by nebulization to treat pulmonary hypertension in acutely ill patients. Although their efficacy as pulmonary vasodilators have been shown to be comparable to inhaled nitric oxide, the local effects of these compounds within the airways have not been determined. We hypothesized that the alkaline diluents of these compounds would lead to increased airway epithelial cell death and ciliary cessation.Methods: Human bronchial epithelial cells were exposed to epoprostenol in glycine and arginine diluents or control fluid. Ciliary beat frequency, lactate dehydrogenase, and total RNA levels were measured before and after exposure. Results were compared between exposure and control groups.Results: Ciliary beat frequency ceased immediately after exposure to epoprostenol with both diluents. Lactate dehydrogenase levels increased by 200% after exposure to epoprostenol and glycine diluent (p < 0.05). Total RNA levels were undetectable after exposure to epoprostenol and arginine, indicating complete cell death and lysis (p < 0.05). Ciliary beat frequency ceased after thirty seconds of exposure to epoprostenol and glycine (p < 0.008). There was no difference between cells exposed to epoprostenol and those exposed only to diluent.Conclusion: Exposure to intravenous formulations of epoprostenol in glycine and arginine that are commonly delivered by nebulizer causes increased cell death and ciliary cessation in bronchial epithelial cells. These findings suggest undesired local effects may occur when these compounds are delivered as inhaled aerosols to patients. ER -