Nephrotoxicity of tiletamine in New Zealand white rabbits.

Tiletamine and zolazepam, the two constituents of Telazol, were evaluated independently to determine which agent was responsible for the nephrotoxicity caused by Telazol in New Zealand White rabbits. Five rabbits were injected i.m. with 32 mg/kg of tiletamine, four animals received 7.5 mg/kg of tiletamine, and five rabbits received 32 mg/kg of zolazepam. Urinalysis was performed and blood urea nitrogen and serum creatinine were monitored for 7 days postinjection. In all five rabbits injected with the high dose of tiletamine, blood urea nitrogen and creatinine rose by 3 days postinjection and increased steadily throughout the week. By 4 days postinjection, urine protein and glucose were elevated and cellular and protein casts were present. No serum chemistry or urine abnormalities were detected in rabbits receiving low doses of tiletamine, zolazepam, or in the four control rabbits. All animals were euthanized and necropsied at 7 days postinjection. Histopathology showed severe renal tubular necrosis in all five rabbits injected with 32 mg/kg tiletamine. Mild nephrosis was present in three of four rabbits injected with 7.5 mg/kg of tiletamine. No lesions were present in the zolazepam-injected or control rabbits. The results of this study show that tiletamine is the constituent responsible for the nephrotoxicity of Telazol in rabbits. They further demonstrate that doses commonly used for anesthetic induction or restraint can produce renal lesions in rabbits.     

Endometrial venous aneurysms in three New Zealand white rabbits.

Hematuria in rabbits has been associated with uterine adenocarcinoma, uterine polyps, renal infarction, urolithiasis, cystitis, bladder polyps, and pyelonephritis. Three adult female New Zealand White rabbits (Oryctolagus cuniculus) developed apparent hematuria, as suggested by blood in their excreta pans. They had been immunized with antigen-adjuvant emulsions, but had uneventful clinical histories. Physical examination disclosed no abnormalities, and laboratory tests, including hematology, serum chemistries, urinalyses, urine cultures, ultrasonography, and intravenous pyelography disclosed mild anemia, hematuria, and proteinuria in two of the rabbits. Antibiotic therapy failed to alleviate clinical signs. Two rabbits were euthanized because of persistent urogenital bleeding and the third rabbit underwent exploratory laparotomy and ovariohysterectomy. Multiple endometrial venous aneurysms were present in the uteri of all rabbits and urogenital bleeding was attributed to episodic bleeding from these lesions. Varices and aneurysms of uterine subserosal and myometrial venous plexuses, but not of endometrial vessels in women have been reported. To our knowledge, endometrial venous aneurysms have not been reported in animals previously. Our findings indicate that the differential diagnoses for sporadic apparent hematuria in female rabbits should include endometrial aneurysms.     

Anesthetic and nephrotoxic effects of Telazol in New Zealand white rabbits.

Telazol was evaluated as an anesthetic for rabbits. Two groups of five rabbits each were injected intramuscularly with 32 or 64 mg/kg of Telazol, and the depth and duration of anesthesia period monitored. At both doses, the righting reflex was lost within 2 minutes postinjection. Animals in both groups responded to noxious stimuli for the duration of the anesthesia. Hematology and urinalyses were performed daily for 7 days postinjection. Hematologic parameters remained unchanged in both groups. In the high-dose group, blood urea nitrogen and serum creatinine levels increased 1 day postinjection and continued steadily throughout the week. Elevations in urine protein and the presence of casts correlated with this increase. In the low-dose group, blood urea nitrogen and creatinine levels increased and protein was present in the urine of four of five rabbits beginning approximately 5 days postinjection. Histologically, severe renal tubular necrosis was evident 7 days postinjection in all high-dose rabbits and in three rabbits in the low-dose group. Our results indicate that Telazol does not produce analgesia in rabbits and is nephrotoxic at both 32 and 64 mg/kg. We conclude that Telazol is contraindicated for use in rabbits.     

Induction and evaluation of atherosclerosis in New Zealand white rabbits

Atherosclerosis was experimentally induced in New Zealand white rabbits by feeding a high cholesterol diet for 12 weeks for screening of drugs against atherosclerosis. After 12 weeks, blood was collected from ear vein for evaluation of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels, then the animals were sacrificed to collect the livers for estimation of cholesterol, and aorta for gross and histopathological evaluations. The elevated levels of serum and liver parameters accompanied by gross and histopathological changes like accumulation of foam cells, atheromatous plaque formation and replacement fibrosis supported the successful induction of atherosclerosis in New Zealand white rabbits.     

一种新的可用于干细胞移植的新西兰白兔青光眼视神经损伤模型

青光眼是一种致盲且不可逆神经退行性疾病,目前还没有能够彻底解决其视野缺失的治疗方法。神经干细胞研究的兴起为该病的治疗带来了可能,且迫切需要一种适用于干细胞移植研究的青光眼造模方法。该实验对新西兰白兔球结膜下注射地塞米松给药,2.5mg/次,一周3次,持续8周。眼底照相显示造模眼眼球屈光间质保持清晰,视乳头凹陷明显扩大、血管呈屈膝状;病理切片显示造模眼视神经明显损伤;海德堡视网膜断层扫描仪(Heidelberg retina tomography,HRT)定量分析显示造模眼盘沿面积减小(1.10±0.88)mm2、杯/盘比增大0.17±0.13,视网膜神经纤维层平均厚度降低(0.44±0.31)mm等青光眼性质病理改变,且均达到极显著水平(P<0.001)。建模成功后,于角膜缘后4mm向造模眼玻璃体注入猕猴神经干细胞,植入5个月后摘取眼球切片,通过荧光显微镜观察到存活的移植细胞。该实验建立了一种简单可靠、重复性强且适用于神经干细胞移植研究的慢性青光眼造模方法。     

Alpha-tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits

In this study, we asked the question "does alpha-tocopherol supplementation prevent an increase in total plasma cholesterol (TPC) concentration and reduce the deposition of cholesterol in arterial plaques of rabbits fed atherogenic diets?" Isocaloric diets containing 0.1% cholesterol to induce atherosclerosis were enriched in one of three fats: saturated fats (SAT), monounsaturated fats (MONO), or n-6 polyunsaturated fats (POLY). Half of each of the three diets were supplemented with 2,500 IU alpha-tocopherol/kg-diet. Unsupplemented diets contained 25 IU alpha-tocopherol/kg-diet. Rabbits supplemented with alpha-tocopherol had plasma alpha-tocopherol concentrations 10-fold higher and an average TPC concentration 31% lower, P = 0.017, than rabbits fed unsupplemented diets. Among the three fat-fed groups, the difference was greatest for the POLY fat fed group (54%, P = 0.041). POLY fat-fed rabbits without alpha-tocopherol supplementation had plasma HDL cholesterol concentrations that were less than half that of rabbits fed other fats, P < or = 0.0001. In general, differences in mean esterified artery cholesterol concentrations among the three fat-fed groups, with and without alpha-tocopherol supplementation, paralleled differences in TPC concentration among the groups. This study suggests that for rabbits fed high pharmacological doses of alpha-tocopherol, atherosclerosis can be diminished in situations where the plasma cholesterol concentrations are also significantly lower.     

Effect of hypercholesterolemia on myocardial function in New Zealand white rabbits

Although hypercholesterolemia is a well-known risk factor for atherosclerosis, little is known about the effect of hypercholesterolemia on cardiac contractile function. The objective of this study was to examine the effect of hypercholesterolemia on myocardial contractility. Fifteen New Zealand white rabbits were fed standard chow (control group) and another 15 were fed a cholesterolenriched diet (HC group) for 12 weeks. The contractile response of ventricular muscle strips was measured in various extracellular calcium concentrations and at different pacing rates. The whole-cell calcium current recording, and mRNA and protein levels of cellular calcium-handling proteins were also analyzed. With 2 mM Ca²⁺ and stimulation at 3 Hz, the contractile force of HC strips was less than that of the controls (3.63±0.20 vs. 4.61±0.50 mN, p<0.05). The time to peak tension was longer for HC strips (93.3±2.16 vs. 82.2±2.81 ms, p < 0.05). The peak L-type calcium inward current density was slightly higher in HC myocytes but did not reach statistical significance (–14.90±0.94 vs. –12.44±0.84 pA/pF, p=0.15). The mRNA level of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA), normalized to GAPDH, was significantly lower in the HC than that in the control group (2.85±0.14 vs. 7.67±0.67, p<0.05), as was the ryanodine receptor (RyR; 0.42±0.06 vs. 0.71±0.13, p<0.05). The mRNA of the Na⁺/Ca²⁺ exchanger (NCX) was statistically higher in the HC group (0.90±0.12 vs. 0.48±0.05, p<0.05). Western blot experiments revealed that protein expression of SERCA in the HC strips decreased, but that of the NCX increased. The protein expression of the dihydropyridine receptor was similar between these two groups. We concluded that hypercholesterolemia results in suppression of the maximal contractile function and in a longer systolic contractile time course. These changes may partially be mediated through a decrease in SERCA and RyR but an increase in NCX expression.     

Response of adult New Zealand white rabbits to enrichment objects and paired housing.

Enhancing the psychological well-being of laboratory animals has received much attention recently. Although many studies have been undertaken to determine the effects of cage enrichment techniques on dogs and nonhuman primates, other than scant empirical observations, little has been done to measure these events objectively in lagomorphs. We studied adult female New Zealand White (NZW) rabbits to learn if, when given the opportunity, individual rabbits would use different enrichment objects placed in their cages, and to determine if rabbits preferred to be in proximity to one another, or apart. Three different objects were evaluated with eight rabbits individually housed in conventional cages. Each object introduced into individual rabbit cages stimulated substantial interaction, especially chewing behavior. Eight other rabbits were pair-housed in a modified caging system with a special access port between two separate cages. When given a choice, rabbits preferred to be in the same cage with other rabbits. In both studies, individual behaviors were monitored, as well as either the type of interaction and percentage of observations spent with each object or, in the housing study, percentage of observations involved with different types of activity, and relative location of the paired rabbits.     

Hematologic values of New Zealand white rabbits determined by automated flow cytometry.

Hematologic values of peripheral blood from normal adult New Zealand White rabbits were determined by five different automated flow cytometers in use in a routine clinical hematology laboratory: Technicon H1, Coulter Counter CC540, Coulter Counter VCS, Sysmex NE8000 and Sysmex R1000. The software designed for human blood analysis was used in all instances without adaptation. The total numbers of white blood cells, red blood cells, reticulocytes and platelets were measured with high precision and accuracy. Except for hemoglobin content, concordance was excellent for all measured and calculated values among the different automated flow cytometers. Determining the white blood cell differential count was more complex. Eosinophils and lymphocytes were quantified reliably by all the automated flow cytometers used. However, the results were rejected by Technicon H1 and Sysmex NE8000 in 50% of the cases. Rabbit basophils were recognized with accuracy by Technicon H1 only. The proportion of polymorphonuclear versus mononuclear white cells was identical when measured with Technicon H1 and Coulter Counter VCS. These results show that the new generation of automated flow cytometers designed for human blood can be used with some limitations for animal studies. They allow the standardization of normal values and comparison of results among or between laboratories. They also introduce new parameters, the value of which is as yet undefined.     

Pathogenicity of Pasteurella multocida A:3 in Flemish giant and New Zealand white rabbits.

Pasteurella multocida A:3 was isolated during an outbreak of pasteurellosis in Flemish Giant (FG) rabbits. Since New Zealand White (NZW) rabbits housed in the same room were not as severely affected as FG rabbits, experimental inoculation was undertaken to determine if FG rabbits were more susceptible than NZW rabbits to pasteurellosis induced by this isolate. Rabbits of each breed were inoculated with P. multocida A:3 and observed for 3 weeks. Four of 5 FG rabbits developed severe clinical disease on days 6, 9, 12 and 14 after inoculation; whereas, the one affected NZW rabbit became ill 14 days after inoculation. All rabbits with clinical disease developed fibrinosuppurative pleuritis, pyothorax and pneumonia which was more severe in FG than NZW rabbits. At necropsy, P. multocida A:3 was isolated from multiple sites of the diseased rabbits. No significant difference (P = 0.099) in the prevalence of lesions between the two breeds was found; however, the score of pneumonia and pleuritis was 3 times greater in FG rabbits than NZW rabbits.     

Pathological study of Streptococcus faecalis antigen-induced arthritis in New Zealand white rabbits

The pathological examination of the rabbit knee joint with antigen-induced arthritis produced by heat-killed Streptococcus faecalis (Str. faec.) as antigen was carried out. Macroscopically, there were findings of acute inflammation about five hours after the injection. Histopathologically, very remarkable acute exudative inflammation was seen 48 hours later. This supported the picture of Arthus reaction. The Arthus reaction disappeared with time, and this supported the view of delayed-type hypersensitivity three weeks later. After that, an obvious chronic inflammation was admitted in 10 weeks. This resembled the histopathological feature of rheumatoid arthritis (RA) when these findings are summarized. It was suggested that arthritis produced by Str. faec. progresses from an acute condition to a one with time. As mentioned above, it thought that Arthus reaction of both immediate hypersensitivity and delayed-type hypersensitivity are necessary in the occurrence of this arthritis.     

Vascular-access-port implantation for serial blood sampling in conscious swine

A method to simplify serial venous blood sampling in miniature pigs was developed. Jugular vein Vascular-Access-Ports (VAP) were implanted in four animals. The mean functional lifetime of these ports was 37.7 +/- 23.0 (S.D.) days with a range of 17 to 77 days. The VAP allowed easy serial blood sampling and intravenous drug administration. Use of these ports in animals restrained in a sling was simple and effective and caused no undue stress to the animal over a 6 to 8 hour experiment. The VAPs were implanted easily and required minimal maintenance. Subcutaneous location of the entire apparatus allowed for group housing of the pigs and decreased the susceptibility of postoperative infection and/or damage. Provided that proper maintenance and careful aseptic sampling techniques are used, the VAP is a relatively easy, safe and reliable alternative to conventional methods of serial blood sampling in swine.     

Restraint device for serial blood sampling of ferrets

A device was designed that effectively restrained unanesthetized ferrets for serial blood sampling from the caudal artery. Materials used for construction were inexpensive and easily obtained. Fabrication was simple and rapid.