Table of Contents Author Guidelines Submit a Manuscript
HPB Surgery
Volume 5, Issue 3, Pages 185-194
http://dx.doi.org/10.1155/1992/28702

The Effects on Toxicity of Circadian Patterning of Continuous Hepatic Artery Infusion

1Department of Surgery, St. Vincent’s Hospital and Medical Center, 153 West 11th Street, New York, NY 10011, USA
2Department of Pathology, St. Vincent’s Hospital and Medical Center, 153 West 11th Street, New York, NY 10011, USA

Received 16 May 1991; Accepted 24 July 1991

Copyright © 1992 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Long term continuous hepatic artery infusion of FUDR was carried out in 34 rats. In the animals who received a constant infusion schedule of 15mg/kg/day all died of toxicity with a mean survival of 9.3 days. If the pattern of the continuous infusion was changed so that over 60% of the infusion was given during the hours of 3pm to 9pm then all of the animals survived the 14 day infusion. If the maximum dose of infusion was changed so that 60% of the infusion was given at night from 3am to 9am the infusion became more toxic and all the animals died in a mean of 5.5 days. Pathologic sectioning of all the livers reflected the above outcomes with the greatest amount of hepatic necrosis in the animals on the night cycles. This study underscores the recent advances in chronobiology demonstrating that for continuous hepatic arterial infusions the timing of delivery is crucial in determining the toxicity.