Continuous Intravenous Infusion in Fischer 344 Rats for Six Months: A Feasibility Study

The feasibility of continuous intravenous infusion as a method for compound administration in studies up to 6 months in duration was assessed in adult male and female Fischer 344 rats (20 per sex). A polyethylene/silastic can-nula was inserted into the jugular vein and exteriorized in the subscapular region of anesthetized rats. Following a 2-week postsurgery recovery period, each animal was fitted with a flexible Velcro saddle/jacket assembly and attached to a tethering system. Infusion pumps were used for infusing sterile saline at a rate of approximately 0.8 ml/hour continuously for 6 months. Animal health was evaluated by monitoring body weight, food consumption, clinical chemistry, hematology, uri-nalysis, and histopathology. At monthly intervals, Brevital sodium (5 mg/kg) was injected into the cannulae for assessing patency, and two animals per sex were submitted for necropsy. Within 4 days postsurgery, mean body weights of male and female rats decreased by approximately 3–5%, compared to presurgery weights. When infusion was initiated 2 weeks following surgery, mean body weights exceeded the presurgery weights by 4–6%. Within 5 days following initiation of infusion, body weight was decreased by 8–10% in all animals. These decreases apparently resulted from reduced food consumption, which occurred as the animals acclimated to the tethering apparatus. Body weight gain and food consumption stabilized and began to increase within 1 week of the initiation of infusion. During the 6-month infusion period, male and female body weights increased by approximately 36%. With the exception of 1 female rat, all animals had patent cannulae at the times they were scheduled for necropsy. Four of the five deaths during the study occurred within 3 days of a cannula patency check, and all deaths were associated with acute renal tubular necrosis that may have resulted from severe hypotension induced by Brevital. Other than minor lesions at the injection site, there were no important histopathologic changes identified in surviving animals that were related to the infusion procedure. Overall, results from this study demonstrated the feasibility of conducting chronic intravenous infusion studies with adult Fischer 344 rats.