Human Reproduction, Vol 13, 2443-2451, Copyright © 1998 by Oxford University Press
KE Rodgers, W Girgis, K St Amand, J Campeau and GS diZerega
Adhesion formation is a major source of postoperative morbidity and
mortality. In this study, the ability of a variety of lazaroid formulations
[the antioxidant 21-aminosteroid PNU74006F (tirilazad) and the
non-steroidal 2-methylaminochroman derivative PNU83,836E] to reduce i.p.
adhesion formation in three rabbit models was examined. In initial studies,
PNU83836E was administered via Alzet miniosmotic pump to the site of
injury. In the sidewall and double uterine horn models, PNU83,836E was
administered via Alzet miniosmotic pump for the entire postoperative
interval. In the sidewall model, there was a dose- dependent reduction in
the area of the sidewall injury that was involved in adhesions. In the
double uterine horn model, PNU83,836E was administered via Alzet
miniosmotic pump to the area of injury for 1, 2, 3 or 7 days.
Administration for as little as 24 h after surgery significantly reduced
the extent of adhesion formation and the reduction was increased if it was
administered for longer. Further studies were conducted in which various
lazaroid formulations were administered as a bolus at the end of surgery.
In both the sidewall and double uterine horn models, administration of
either PNU83,386E (in citrate buffer) or PNU74006F (in cyclodextrin or
lipid emulsion vehicles) at the end of surgery reduced adhesion formation.
Administration of a bolus of PNU74006F 10 min prior to initiation of
surgery with or without additional treatment at the end of surgery further
increased its efficacy in the reduction of adhesion formation.
Administration of a minimum of 1.5 mg before and after surgery (3 mg total)
was required for maximal efficacy. These studies demonstrate that pre- and
postoperative administration of either a steroidal (PNU74006F) or
non-steroidal (PNU83,836E) lazaroid intraperitoneally reduced the formation
and reformation of postoperative adhesions in three animal models.
ARTICLES
Reduction of adhesion formation in rabbits by intraperitoneal administration of lazaroid formulations
University of Southern California, Department of Obstetrics and Gynecology, Livingston Research Center, Los Angeles 90033, USA.
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