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Toxicity of prolonged high dose inhaled PGE1 in ventilated neonatal pigs
Beena G Sood1, Elizabeth J Dawe, Krishna Rao Maddipati
1Division of Neonatal-Perinatal Medicine, Children's Hospital of Michigan, 3901 Beaubien Blvd., 4H42 Detroit, MI 48201, USA. bsood@med.wayne.edu <bsood@med.wayne.edu>
Insights
Inhaled prostaglandin E1 (PGE1) showed minimal pulmonary toxicity in piglets. High-dose inhaled PGE1 appears safe for prolonged use in newborn piglets, with no adverse cardiorespiratory effects observed.
Area of Science:
- Neonatal physiology
- Pulmonary toxicology
- Prostaglandin research
Background:
- Mechanical ventilation is crucial for neonatal care but can cause lung injury.
- Prostaglandin E1 (PGE1) has potential therapeutic applications, necessitating safety evaluations.
- Understanding the toxicity of inhaled PGE1 (IPGE1) is vital for its clinical use.
Purpose of the Study:
- To assess the toxicity of high-dose inhaled PGE1 (IPGE1) in healthy, mechanically ventilated piglets.
- To evaluate the cardiorespiratory, hematologic, and histopathologic effects of IPGE1 exposure.
Main Methods:
- Mechanically ventilated piglets received either high-dose IPGE1 or saline (control) for 24 hours.
- Cardio-respiratory parameters, blood counts, and electrolytes were monitored.
- Lung histology was assessed by a pathologist for injury severity and extent.
Main Results:
- No adverse cardiorespiratory effects, bronchial irritation, or hypernatremia were linked to IPGE1.
- Alveolar edema and inflammation were observed in both groups, likely due to mechanical ventilation.
- IPGE1-treated animals showed focal bronchial epithelial ulceration, flattening, and cilia loss.
Conclusions:
- High-dose IPGE1 inhalation did not cause significant adverse effects in healthy piglets.
- Pulmonary toxicity was minimal even after 24 hours of exposure.
- Prolonged inhaled PGE1 appears safe in newborn piglets.
Objective:
To study the toxicity of inhaled PGE1 (IPGE1) in healthy ventilated piglets.
Methods:
Mechanically ventilated anesthetized piglets received either high dose IPGE1 (IPGE1 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 IPGE1. There was no evidence of adverse cardio-respiratory effects, bronchial irritation or hypernatremia related to IPGE1. Diffuse/multifocal alveolar edema and focal polymorphonuclear infiltration was observed in both the control and IPGE1 groups suggesting that alveolar alterations may be secondary to effects of mechanical ventilation. The most distinct histomorphological abnormalities observed in the IPGE1 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 IPGE1 was not associated with adverse cardiorespiratory effects, bronchial irritation, or hypernatremia and produced minimal signs of pulmonary toxicity even after 24h. Prolonged inhalation of high dose PGE1 therefore appears safe in newborn piglets.
