Acute behavioral effects of intrapleural OK-432 (Picibanil) administration in preterm fetal sheep.
OBJECTIVE
To develop a model to study the fetal effects of intrapleural infusion of OK-432 (Picibanil), a pleurodesis agent derived from killed Gram-positive streptococci.


METHODS
OK-432 (0.1 mg, n = 5), or normal saline (n = 5) were infused over 20 min into the pleural space of chronically instrumented preterm fetal sheep at 0.7 gestation. Fetal physiological parameters, including breathing and nuchal activity were monitored in utero from 6 h before infusion until 12 h afterward, and fetuses were killed after 7 days recovery.


RESULTS
OK-432 was associated with transient suppression of fetal EEG activity, breathing and body movements from 3-6 h after infusion. Hypotension and hypoxia did not occur. At postmortem, local pleural adhesions were seen around the site of OK-432 infusion but not in saline treated fetuses.


CONCLUSIONS
Intrapleural administration of OK-432 is associated with marked but transient fetal behavioral effects. This model will enable preclinical investigation of the neural and cardiovascular safety of OK-432 at a clinical relevant stage of development.
Cowie
Rosalind V
RV
Department of Physiology, University of Auckland, Auckland 1023, New Zealand.
Stone
Peter R
PR
Parry
Emma
E
Jensen
Ellen C
EC
Gunn
Alistair J
AJ
Bennet
Laura
L
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002916:Chylothorax / Q000188:drug therapy / Q000662:veterinary; D005333:Fetus / Q000187:drug effects*; D006340:Heart Rate, Fetal / Q000187:drug effects; D010844:Picibanil / Q000008:administration & dosage / Q000009:adverse effects*; D035422:Pleural Cavity / Q000187:drug effects / Q000473:pathology; D012119:Respiration / Q000187:drug effects; D012756:Sheep / Q000502:physiology*
D010844:Picibanil