Tissue Isotope Clearance III. Variability Attributed to Age, Sex, and Core Temperature in Rats

Abstract

While conducting experiments to determine drug effects upon subcutaneous isotope clearance using the method of Kety (l), it was observed that control clearances varied appreciably in successive groups of rats. Some of these groups were known to differ in sex and age. Also, animals anesthesized with a barbiturate (which was used in these experiments) tend to have depressed core temperatures which may vary with the ambient temperature. It was hypothesized, therefore, that differences in age, sex and core temperature might account for tGe observed variability in subcutaneous isotope clearance. Two studies (2, 3) have shown that isotope clearance rates fmm injection sites can vary with core ternperatme. However, no specific studies demonstrating the e€€ects of age and sex and their interaction with core temperature on isotope clearance rates have been found.The pwpuse of the present study was to test the effects (both independent and interactive) of age, sex md core temperature upon isotope clearances following injection of the isotope in saline solution.In addition, two local anesthetics, prilocaine and tetracaine which were reported to have opposite effects upon clearance rate (4) were added to the isotope solutions as positive controls under all the conditions of the experimental design.Methods. All rats used were of the Strain CD-1 (Sprague-Dawley derived) and were obtained from Charles River. Nine rats of each sex in each of four designated age categories were selected and randomly assigned to three core temperature ranges, 93.5"-95.5", 100"-102", and 105.0*-107"F.The age categories were: (a) immature (about 45 days old), (b) pubescent (about 84 days old), (c) mature (about 5 mo old) and (d) aged (about 12 mo old). Each rat was anesthetized with a mixture of pentobarbital (35 mg/kg) and barbital (90 mg/kg) and was equilibrated to one of the three core temperature ranges by adding or removing radiant heat sources. Core temperature was monitored with a Yellow Springs Rectal thermister and a tele-thermometer, YSI Model 47. Three subcutaneous injections were given in random sequence to each rat at nearby sites in the dorsal-lumbosacral m i d h e , Each injection solution contained 0-1 ml of 1311-4-iodoantipyrine (IAP) in sali buffer (pH7.4) at physio1og.k osmoIarStygr, En addition, the positive c o n t d injections contained either 0. € % tetracaine or 2,W p d o c~i n e wtkh appropriate adjustment of osmo1,anty and pH.The c€earance of IAP from the in@cticm site was monitored with a Nuclear ChEcqp surgical =intillation p m k (Model 931) which was connected to an appropriate remr&ng apparatus. Twenty min were allowed between injections for clearance determinations. All dntgs were mixed freshly from powders on the day of the experiment. Detailed methods were described previ-The data were analyzed separately for each drug condition as a 4 x 3 X 2 completely crossed, fixed effects analysis of variance design. During the experiments, two aged rats died; the grand mean was substituted for the clearance values for the appro...