Toxicity of prolonged high dose inhaled PGE1 in ventilated neonatal pigs.
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.


CONCLUSIONS
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.
Sood
Beena G
BG
Division 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>
Dawe
Elizabeth J
EJ
Maddipati
Krishna Rao
KR
Malian
Monica
M
Chen
Xinguang
X
Galli
Robert
R
Rabah
Raja
R
D000280:Administration, Inhalation; D000336:Aerosols; D000527:Alprostadil / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008168:Lung / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011652:Pulmonary Circulation / Q000187:drug effects; D012121:Respiration, Artificial; D013552:Swine
D000336:Aerosols; D000527:Alprostadil