Continuous intravenous infusion in athymic (nude) rats: an animal model for evaluating the efficacy of anti-cancer agents

Abstract

SummaryThe athymic (nude) rat (rnu/rnu) has been used for a number of years in research into various human tumours involving xenotransplantation. We now report the validation of a continuous intravenous infusion method in nude rats using a tail cuff tether, which enables the study of the efficacy of novel anti-cancer materials in this mutant strain, using intravenous infusion and with no restriction of the animals or of the tumour implantation sites by jackets.Ten animals each had a cannula surgically implanted into the vena cava via the femoral vein and exteriorized via a tail cuff. Animals were housed singly in conventional cages following surgery. Following a recovery period of 5 days all animals were continuously infused with physiological saline at an infusion rate of 0.5 ml/h for a further 37 days. Body weights and food consumption were recorded weekly. Blood samples were taken approximately 14 days post-surgery and analysed for haematology and clinical chemistry parameters. All animals were successfully cannulated, and no unexpected adverse clinical signs were noted during the recovery period and the 37 days of infusion.The results demonstrate that it is possible to surgically cannulate the femoral vein of athymic (nude) rats and infuse them in conventional cages for a period of up to 37 days with minimal adverse effects. The minimal restraint required provides benefits both to the animal and to the conduct of studies such as assessment of tumour growth in the absence of a jacket. Recent work has demonstrated that the same techniques can be successfully applied to the nude mouse. Keywords Continuous intravenous infusionj nude rat; anti-cancer agentsEffective rat infusion models have been developed over the last two decades. The most common infusion model consists of a surgically implanted cannula into the jugular vein with exteriorization at the scapular region. The animals wear a jacket connected to a steel spring and tethering device to protect the cannula (Francis et al. 1992).At Inveresk Research we use a modified technique based on a publication by Jones and Hynd 119811 and modified by Cave et al. (1995) for long-term infusion in the rat, involving surgical implantation of a cannula Correspondence to: Hans van Wi;k into the caudal vena cava via the femoral vein, with exteriorization at the tail, within a protective tail cuff.Following safety assessment studies in the Sprague-Dawley rat with a novel anti-cancer compound, an efficacy study was required in athymic (nude) rats. The objective of this efficacy study was to assess the anti-tumour effect of a novel anti-cancer agent on a human tumour subcutaneously implanted in rnu/rnu nude rats (Schuurman 1995), while monitoring treatment-related toxic effects in the same animals, within a Good Laboratory Practice (GLP) environment.

Construction and Validation of a Microprocessor Controlled Extracorporal Circuit in Rats for the Optimization of Isolated Limb Perfusion

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Single fibers of skeletal muscle as a novel graft for cell transplantation to the heart

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