Long term continuous hepatic artery infusion of FUDR was carried out in 34 rats. In the animals whoreceived 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 duringthe hours of 3pm to 9pm then all of the animals survived the 14 day infusion. If the maximum dose ofinfusion was changed so that 60% of the infusion was given at night from 3am to 9am the infusionbecame more toxic and all the animals died in a mean of 5.5 days. Pathologic sectioning of all the liversreflected the above outcomes with the greatest amount of hepatic necrosis in the animals on the nightcycles. This study underscores the recent advances in chronobiology demonstrating that for continuoushepatic arterial infusions the timing of delivery is crucial in determining the toxicity.
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机译：在34只大鼠中进行了FUDR的长期连续肝动脉输注。每天接受15mg / kg /天的固定输注的动物均死于毒性，平均存活时间为9.3天，如果连续输注的方式发生变化，以便在下午3点至输卵期间给予超过60％的输注晚上9点，所有动物在输注14天后均存活。如果更改最大输注剂量，以便在晚上3点至上午9点之间进行60％的输注，则输注的毒性会更大，所有动物平均死亡5.5天。在夜间动物中，所有肝脏的病理切片均反映了上述结果，其中肝坏死的数量最多。这项研究强调了时序生物学的最新进展，表明对于连续性肝动脉输注来说，分娩的时机对确定毒性至关重要。
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