Toxicity of prolonged high dose inhaled PGE1 in ventilated neonatal pigs

Objective: To study the toxicity of inhaled PGE(1) (IPGE(1)) in healthy ventilated piglets. Methods: Mechanically ventilated anesthetized piglets received either high dose IPGE(1) (IPGE(1) group) or nebulized saline (control group) continuously for 24h. Cardio-respiratory parameters, complete blood counts and serum electrolytes were monitored. Lung histology was evaluated by a masked pathologist for the severity (minimal, moderate, and severe) and extent (focal, multifocal, and diffuse) of histologic injury. Results: Ten neonatal pigs were instrumented. Four received nebulized saline and six received high dose IPGE(1). There was no evidence or adverse cardio-respiratory effects, bronchial irritation or hypernatremia related to IPGE(1). Diffuse/multifocal alveolar edema and focal polymorphonuclear infiltration was observed in both the control and IPGE(1) groups suggesting that alveolar alterations may be secondary to effects of mechanical ventilation. The most distinct histomorphological abnormalities observed in the IPGE(1) animals were focal ulceration, flattening of the bronchial epithelium and loss of cilia of moderate to severe degree in the trachea and bronchi. Conclusion: In healthy piglets, inhalation of high dose IPGE(1) was not associated with adverse cardiorespiratory effects, bronchial irritation, or hypernatremia and produced minimal signs of pulmonary toxicity even after 24 h. Prolonged inhalation of high dose PGE(1) therefore appears safe in newborn piglets. (C) 2008 Elsevier Ltd. All rights reserved.