Effect of in-house transport on murine plasma corticosterone concentration and blood lymphocyte populations.

The effect of in-house transport on plasma corticosterone concentration and blood lymphocyte populations of laboratory mice was investigated. Mice were transported within a research facility at 0900 hours in a pattern designed to simulate that commonly used by investigators prior to experimental manipulation. Plasma corticosterone concentration and WBC count were determined at 0.25, 2, 4, 8, 12, and 24 hours after transport. A significant (P less than 0.05) increase in plasma corticosterone concentration was seen in mice immediately after transport. The normal circadian rhythm of plasma corticosterone concentration was altered for the subsequent 24-hour period. Corresponding significant (P less than 0.05) decreases in total WBC numbers, lymphocyte count, and thymus gland weight were observed. The decrease in total blood lymphocyte numbers at 4 hours was reflected in B- and T-lymphocyte populations. The subsequent acute increase in plasma corticosterone concentration was associated with alterations in the cellular components of the immune system. Results of the study indicated that routine in-house transport of laboratory mice should be considered a stressful stimulus.

Vitamin A deficiency decreases natural killer cell activity and interferon production in rats.

We examined the effect of vitamin A deficiency on natural killer (NK) cell activity and interferon (IFN) production. Rats were weaned at 16 or 21 d of age onto semisynthetic diets containing either 0 or 4 micrograms retinol/g diet. At the time of study, retinol-depleted rats had serum vitamin A concentrations less than 7% of those of pair-fed controls. In two studies, rats exhibited no external signs of retinol deficiency, but with further depletion some symptoms were observed. Splenic NK cell activity against chromium-51-labeled YAC-1 cells was significantly decreased in vitamin A-depleted rats (22-80% of values for control rats, depending on the degree of retinol deficiency), regardless of the ratio of effector to target cells used. When vitamin A-depleted rats were repleted orally with retinol, NK cell activity was consistently normalized. To understand the possible mechanisms involved in decreasing NK cell activity, we investigated IFN production by concanavalin A-stimulated spleen cells from vitamin A-depleted, from repleted and from control animals. IFN titers were significantly decreased (22-33% of values for control rats) in supernatants of spleen cell cultures of the vitamin A-depleted rats. Repletion with vitamin A resulted in IFN activities ranging from 80 to 130% of controls. Adding alpha/beta IFN in vitro to the spleen cells of vitamin A-depleted animals increased their NK cell activity. The number of spleen cells reacting with a monoclonal antibody specific for rat NK cells was slightly lower in retinol-depleted rats, but not enough to account for the differences in NK cell and IFN activities. These data suggest that vitamin A deficiency affect the nonspecific arm of the immune system, possibly by altering the functional capacity of cells to produce lymphokines needed for the generation of an appropriate cytolytic response.

On the antipyrine test in laboratory animals. Studies in the dog and monkey.

The antipyrine (AP) test has been challenged in species other than humans on the grounds that, in some nonhuman species, particularly on induction, hepatic blood flow may become as prominent a factor in AP clearance as hepatic metabolism. Therefore, we investigated in dogs and monkeys the disposition of AP to determine how well AP serves as a model drug to indicate changes in rates of hepatic clearance. After administration of an oral solution of AP (5 mg/kg) to control dogs, the percentage of the dose absorbed was 98%, based on urinary and fecal excretion of AP and its metabolites. Despite complete AP absorption, absolute bioavailability of AP was 78 +/- 12% under basal conditions, suggesting that AP does undergo some degree of presystemic elimination, approximately 22%. After PB administration of 20 mg/kg/day for 9 days, po, AP bioavailability decreased to 60 +/- 14%. The systemic clearance of AP increased from 9.4 +/- 2.3 ml/min/kg under basal conditions to 27.5 +/- 4.6 ml/min/kg following PB. PB decreased mean plasma AP half-life from 71.5 min under basal conditions to 27.7 min, and mean hepatic blood flow increased from 0.49 liters/min to 0.63 liters/min. Induction doubled the hepatic extraction ratio for AP to 0.4 from 0.2 under basal conditions. In beagle dogs after PB pretreatment, 97% of the total systemic clearance of AP was estimated to be due to enhanced hepatic AP metabolism, only 3% to increased hepatic blood flow. Therefore, for dogs under both basal and induced conditions it is concluded that AP clearance reflects predominantly hepatic AP metabolism, being negligibly influenced by hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin A depletion and repletion: effects on antibody response to the capsular polysaccharide of Streptococcus pneumoniae, type III (SSS-III).

To determine the ability of young rats to produce antibody against pneumococcal polysaccharide (SSS-III), weaning rats were fed a semipurified diet containing no retinol (A-) or 4 micrograms retinol/g diet (A+). Splenic antibody response specific to SSS-III was 17% (p less than or equal to 0.05) of control for A- Sprague-Dawley rats; similarly, the response of retinol-depleted Lewis rats was 22% (p less than or equal to 0.05) of pair-fed controls. No kinetic differences were observed in the antibody response between A- and control Lewis rats. Retinol depletion more markedly reduced the antibody response of male rats than female rats despite equally low tissue retinol concentrations. For both strains, retinol repletion near the time of immunization normalized antibody production. When male Lewis rats were fed the A- diet longer, the antibody response of A- rats was only 3% of pair-fed controls; repletion again normalized antibody production. Thus, retinol supplementation near the time of immunization can restore the immune response in previously compromised A- rats.

An evaluation of three anaesthetic regimes in the gray short-tailed opossum (Monodelphis domestica).

The effect of several anaesthetic agents on the gray short-tailed opossum (Monodelphis domestica) was investigated. Pentobarbitone sodium at a dose of 50 mg/kg sedated the animals but did not produce analgesia or anaesthesia. A combination of ketamine hydrochloride and xylazine at 40 mg/kg and 5 mg/kg, respectively, sedated the animals, but anaesthetic levels were not attained. Halothane was most effective in producing anaesthesia in Monodelphis domestica. Hypothermia was a major side effect with all three anaesthetic regimes.

Laboratory management of the ferret for biomedical research.

Ferrets have become an increasingly important animal in biological research. This paper discusses unique aspects of the ferret's anatomy, reproductive behavior, husbandry, and diseases as they relate to the research use of this animal.

Ventriculoatrial conduction in swine during cardiac pacing: animal model for retrograde conduction.

Studies on cardiac conduction disorders and pacemaker tachycardias are usually conducted in patients because the phenomenon of ventriculoatrial (retrograde) conduction resulting from ectopic beats and pacing the ventricles has only been reported in humans. This study was conducted to characterize the ventriculoatrial (VA) conduction and retrograde P wave electrogram (EGM) amplitude and slew rate in 10 anesthetized pigs. Three transvenous pacemaker leads were positioned in the heart: one in the right atrial appendage, one in the sinoatrial (SA) node region, and another in the apex of the right ventricle. Ventriculoatrial conduction always occurred when the heart was paced from the right ventricle. There was a significant difference (p less than 0.05) between the amplitude and slew rate of the intrinsic P wave EGM (6.36 +/- 1.88 mV, 1.03 +/- 0.35 mV/msec) compared to the retrograde P wave EGM (3.12 +/- 1.37 mV, 0.57 +/- 0.18 mV/msec) detected at the SA node region. However, there was no significant difference between the intrinsic P wave EGM (4.81 +/- 2.01 mV, 0.40 +/- 0.26 mV/msec) and the retrograde P wave EGM (4.13 +/- 3.74 mV, 0.13 +/- 0.05 mV/msec) detected in the atrial appendage. The advantage of positioning an electrode in close proximity to the SA node for optimum atrial EGM detection and differentiation from retrograde P wave EGM is evident. The VA conduction time (178.5 +/- 8.5 msec) was significantly greater (p less than 0.01) than the antegrade conduction time (120.0 +/- 18.2 msec). The pig with its VA conduction is a useful model for pacemaker-induced tachycardias and for in vivo testing of drugs and/or pacemaker programs that can be utilized for controlling or preventing them.

Swine as an in vivo model for electrophysiologic evaluation of cardiac pacing parameters.

Pre-clinical studies of cardiac pacemakers and new electrodes, materials, and designs are for the most part conducted in dogs. Dogs, however, have electrophysiological differences which may preclude accurate translation to clinical trials. The purpose of this study was to develop normal electrophysiological parameters for an animal whose cardiovascular system more closely resembles that of man than any nonprimate animal. The threshold (voltage and current) strength-duration curves of the pig showed the same inverse relationship between the pulse duration and threshold requirements as other species. At 0.5 ms the atrium had 3.5-5.5 times greater energy requirements, over twice the current (2.04 mA vs 0.72 mA) and twice the voltage (0.75 mV vs 0.32 mV) requirements when compared to the ventricles. The pig's S-A nodal P-wave was superior in amplitude (7.80 +/- 1.80 mV vs 4.28 +/- 2.27 mV) and the slew rate was faster (1.30 +/- 0.56 mV/ms vs 0.44 +/- 0.50 mV/ms) compared to that of the atrial appendage. The pig's left ventricular myocardial R-wave had significantly greater amplitude (19.00 +/- 6.44 mV vs 10.70 +/- 4.34 mV) and faster slew rate (1.60 +/- 0.62 mV/ms vs 0.90 +/- 0.30 mV/ms) compared to the right ventricular endocardial R-wave. The electrophysiological parameters of the pig were more similar to those of man than the dog; therefore, the pig is a useful animal model for electrophysiological studies and the testing of pacemaker equipment.