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OBJECTIVES Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction. METHODS New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n = 94), postnatal day 4 (n = 11), or postnatal day 7 (n = 52). Hearts were explanted 1 day postsurgery to confirm ischemic injury, at 1 week postsurgery to assess cardiomyocyte proliferation, and at 3 weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean ± standard deviation. RESULTS Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3% ± 5.4% vs 42.3% ± 4.7%, P = .9984). Echocardiography confirmed severely reduced ejection fraction at 1 day after postnatal day 1 myocardial infarction (33.7% ± 5.3% vs 65.2% ± 5.5% for postnatal day 1 sham, P = .0001), but no difference at 3 weeks after postnatal day 1 myocardial infarction (56.0% ± 4.0% vs 58.0% ± 3.3% for postnatal day 1 sham, P = .2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2% ± 1.8% vs 58.5% ± 5.8% for postnatal day 4 sham, P = .0109) and postnatal day 7 myocardial infarction (39.0% ± 7.8% vs 60.2% ± 5.0% for postnatal day 7 sham, P

The nanostructural response of New Zealand white rabbit Achilles tendons to a fatigue damage model was assessed quantitatively and qualitatively using the endpoint of dose assessments of each tendon from our previous study. The change in mechanical properties was assessed concurrently with nanostructural change in the same non-viable intact tendon. Atomic force microscopy was used to study the elongation of D-periodicities, and the changes were compared both within the same fibril bundle and between fibril bundles. D-periodicities increased due to both increased strain and increasing numbers of fatigue cycles. Although no significant difference in D-periodicity lengthening was found between fibril bundles, the lengthening of D-periodicity correlated strongly with the overall tendon mechanical changes. The accurate quantification of fibril elongation in response to macroscopic applied strain assisted in assessing the complex structure-function relationship in Achilles tendons.

A variety of gadolinium (Gd) based nanoparticles (NPs) were synthesized due to the unique magnetic properties of Gd-containing rare earth compounds and the particularity of micro/nano-materials, which were then incorporated into hydroxyapatite (HA) to obtain inorganic-organic composite materials. Then, HA/Gd NPs containing slow-release transforming growth factor (TGF-β1) were harvested. Adipose-derived stem cells (ADSCs) were extracted from the adipose tissue of a four-month-old New Zealand white rabbit. HA/Gd NPs were attached to absorbable gelatin sponge to obtain HA/Gd NPs/gelatin sponge composite scaffold. In addition, the third generation ADSCs were taken and cultured in the composite scaffold, so that ADSCs-HA/Gd bio-nanocomposites were obtained. The in vitro culture test of osteoblast MC3T3-E1 showed that Gd-containing NPs had good biocompatibility. The prepared HA/Gd NPs loaded with TGF-β1 were spherical, with an average particle size of (9.16 ± 3.16) μm. The NPs were easy to aggregate and adherent. Enzyme-linked immunosorbent assay (ELISA) test results showed that TGF-β1 in NPs was sustained and released continuously for 29 days. HA/Gd NPs/gelatin sponge composite scaffold combined with ADSCs were co-cultured for three days, and the electron microscope showed that the HA/Gd NPs were dispersed, and the cells could adhere and grow well. Then, animal models of rabbit knee articular cartilage defects were established and were rolled into three groups (ADSCs-HA/Gd nano group, HA/Gd nano scaffold group, and blank control). The repair area of the rabbit knee of ADSCs-HA/Gd nano group was smooth and flat, the scaffold was absorbed, the toluidine blue stain was positive, and the type II collagen immunohistochemical stain was positive. In general, ADSCs-HA/Gd nanomaterials were helpful for chondrogenic cell differentiation and had certain adoption prospects in the field of tissue engineering to repair cartilage defects.

OBJECTIVE Temporary parent vessel occlusion performed to establish a high-flow interpositional bypass carries the risk of infarcts. The authors investigated the feasibility of a novel technique to establish a high-flow bypass without temporary parent vessel occlusion in order to lower the risk of ischemic complications. METHODS In 10 New Zealand white rabbits, a carotid artery side-to-end anastomosis was performed under parent artery patency with a novel endovascular balloon device. Intraoperative angiography, postoperative neurological assessments, and postoperative MRI/MRA were performed to evaluate the feasibility and safety of the novel technique. RESULTS A patent anastomosis was established in 10 of 10 animals; 3 procedure-related complications occurred. No postoperative focal neurological deficits were observed. The MRI/MRA findings include no infarcts and bypass patency in 50% of the animals. CONCLUSIONS The authors demonstrated the feasibility of an endovascular assisted, nonocclusive high-flow bypass. Future refinement of the device and technique in an animal model is necessary to lower the complication rate and increase patency rates.

Background The identification of biocomposites that improve cell adhesion and reduce bone integration time is a great challenge for implantology and bone reconstruction. Aim Our aim was to evaluate a new method of chemisorption deposition (CD) for improving the biointegration of hydroxyapatite-coated titanium (HApTi) implants. CD method was used to prepare a calcium fructoborate (CaFb) coating on a HApTi (HApTiCaFb) implant followed by evaluation of histological features related to bone healing at the interface of a bioceramic material in an animal model. Methods The coating composition was investigated by high-performance thin-layer chromatography/mass spectrometry. The surface morphology of the coating was studied by scanning electron microscopy (SEM), before and after the in vitro study. We implanted two types of bioceramic cylinders, HApTi and HApTiCaFb, in the femur of 10 New Zealand White (NZW) rabbits. Results The release of CaFb from HApTiCaFb occurred rapidly within the first three days after phosphate-buffered saline immersion; there was then a linear release for up to 14 days. SEM analysis showed similar morphology and particle size diameter for both implants. Around the porous HApTiCaFb implant, fibrosis and inflammation were not highlighted. Conclusions Easily applied using CD method, CaFb coatings promote HApTi implant osseointegration in the femur of NZW rabbits.

lt;bgt;Background and Objective:lt;/bgt; The sex pre-selection for offspring before conception is desirable demand especially for the breeding program of farm animals. This study aimed to evaluate the preconception treatment of monovalent and divalent ions on the primary sex ratio, ovarian structures and serum minerals levels in New Zealand white rabbit does.lt;bgt;Materials and Methods:lt;/bgt; Nine New Zealand white rabbits doelt;igt;lt;/igt;(5.4±0.61 months of age and 2.4±0.35 kg of body weight) were used. Rabbits in the 1lt;supgt;stlt;/supgt; group were given drinking water only (control). While the 2lt;supgt;ndlt;/supgt; and 3lt;supgt;rdlt;/supgt; groups were given 1% of (calcium and magnesium) and (sodium and potassium) in daily drinking water, respectively for 15 days before mating. The embryos of each group were individually collected after three days of mating for primary sex detection using SRY (Sex Determining Region Y) Polymerase Chain Reaction (PCR) assay. Mineral analyses for all studied animals were weekly detected in serum before and after mating.lt;bgt;Results:lt;/bgt; The primary sex ratio for embryos of rabbits does receive (Na+K) produced more males (69.7%) while (Ca+Mg) administrated rabbits does produce more females (72.2%). The mineral treatment leads to a significant increase in the number of corpus luteum, total embryos, follicles bleeding and a significant decline in the count of large follicles. Also, there was no significant change in serum Na and Ca levels in the treated groups compared to the control.lt;bgt;Conclusion:lt;/bgt; The preconception administration of Ca+Mg could produce more females while Na+K could produce more males without adverse side effects on serum minerals concentration.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a condition documented in humans and animals exposed to chronic steroid administration. The rabbit has become a preferred animal model for investigating the pathogenesis and treatment of SONFH due to its shared femoral vascular anatomy with human patients, relative size of the femoral head, and general fecundity. However, morbidity and mortality are frequent during the steroid induction period, prior to surgical manipulation. These problems are poorly reported and inadequately described in the literature. In this study, we report the clinical, gross, and histopathologic findings of New Zealand white (NZW) rabbits undergoing the steroid induction phase of the SONFH model. Severe weight loss (>30%), lipemia, hypercholesterolemia, hyperglycemia, and elevations in ALT and AST were consistent findings across all rabbits, although these changes did not differentiate asymptomatic rabbits from those that became clinically symptomatic or died. Euthanized and spontaneously deceased rabbits exhibited hepatomegaly, hepatic lipidosis/glycogenosis, and hepatocellular necrosis, in addition to a lipid-rich and proteinaceous thoracic effusion. A subset of rabbits developed opportunistic pulmonary infections with Bordetella bronchiseptica and Escherichia coli and small intestine infections with Lawsonia intracellularis superimposed on hepatic and thoracic disease. Together, these findings allowed us to establish a clinical decision-making flowchart that reduced morbidities and mortalities in a subsequent cohort of SONFH rabbits. Recognition of these model-associated morbidities is critical for providing optimal clinical care during the disease induction phase of SONFH.

The current study was designed to describe the prenatal developmental stages of the rabbit tongue. Thirty-five embryos of prenatal ages (E16, E19, E23, E25, E28, and Postnatal) were obtained from New Zealand white (NZW) rabbit. The primordia of the tongue were observed on the foundation as early as day 16 prenatal age (E16). The first primordia of lingual papillae were observed that including the primordia of circumvallate papillae at day 19 prenatal (E19). Thickenings of lingual epithelium developed at 19 day prenatal of embryo. At day 23-25 pc, the presence of primordia of foliate papillae was shown in addition to primordia of the fungiform and filiform papillae were found. The development of the final shape of the tongue is a longstanding process that occurs during the prenatal and postnatal life. The first primordia of gustatory papillae appear, and only later primordia of mechanical papillae are formed. In conclusion, the morphogenesis of the tongue and its lingual papillae discussed its herbivorous nature of feeding.

When using a prosthetic material in hernia repair, the behaviour of the mesh at the peritoneal interface is especially important for implant success. Biomaterials developed for their intraperitoneal placement are known as composites and are made up of two different-structure materials, one is responsible for good integration within host tissue and the other is responsible to make contact with the viscera. This study examines the behaviour at the peritoneal level of two composites, the fully degradable Phasix-ST® and the partially degradable Symbotex®. A polypropylene mesh (Optilene®) served as control. Sequential laparoscopy from 3 to 90 days, in a preclinical model in the New Zealand white rabbit, allowed monitoring adhesion formation. Morphological studies were performed to analyse the neoperitoneum formed in the repair process. Total macrophages were identified by immunohistochemical labelling. To identify the different macrophage phenotypes, complementary DNAs were amplified by qRT-PCR using specific primers for M1 (TNF-α/CXCL9) and M2 (MRC1/IL-10) macrophages. The percentage of firm and integrated adhesions remained very high in the control group over time. Both composites showed a significant decrease in adhesions at all study times and in qualitative terms were mainly loose. Significant differences were also observed from 7 days onwards between the two composites, increasing the values in Phasix over time. Neoperitoneum thickness for Phasix was significantly greater than those of the other meshes, showing mature and organized neoformed connective tissue. Immunohistochemically, a significantly higher percentage of macrophages was observed in Symbotex. mRNA expression levels for the M2 repair-type macrophages were highest for Phasix but significant differences only emerged for IL-10. Fewer adhesions formed to the Symbotex than Phasix implants. Ninety days after implant, total macrophage counts were significantly higher for Symbotex, yet Phasix showed the greater expression of M2 markers related to the tissue repair process.

The purpose of this work was i) to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model of dexmedetomidine (DEX) in New Zealand White rabbits, ii) to investigate the influence of the age and weight of the animals on the model parameters, and iii) to assess the linearity of DEX PKs in the examined dose range. This was a prospective, crossover study, using a total of 18 New Zealand White rabbits. DEX was administered as a single intravenous bolus injection in the doses from 25 to 300 μg kg-1 . Each New Zealand White rabbit was given the same dose of drug in its three developmental stages. To determine the DEX PK, seven blood samples were taken from each animal. The pedal withdrawal reflex was the PD response used to assess the degree of sedation. Nonlinear mixed effects modelling was used for the population PK/PD analysis. The typical value of elimination clearance was 0.061 L min-1 and was 35% higher in younger New Zealand White rabbits compared with older animals. The PK of DEX was linear in the examined concentration range. Age-related changes in sensitivity to DEX were not detected. The results suggest that due to the pharmacokinetics, younger animals will have lower DEX concentrations and a shorter duration of sedation than older animals given the same doses of DEX per kg of body weight.

Lighting regimes are possibly used as a strategy to improve rabbit production in tropical regions; on this background, this study was conducted to assess the possible role of different light (L):dark (D) regimes in improving growing New Zealand white rabbit’s performance. Sixty-four growing rabbits were randomly divided into four groups. Rabbits of the first group (C) were exposed to 12 h of light (from 10.00 to 22.00 h). Rabbits of the second group (T1) were exposed to 12 h of light (from 22.00 to 10.00 h). The third group (T2) was exposed to 8 h of light (from 10.00 to 18.00 h), while the fourth group (T3) was exposed to 8 h of light (from 22.00 to 06.00 h). Temperature-humidity index values ranged between 27.00 and 28.87, indicating exposure of growing rabbits to very severe heat stress. Body weight (BW), body weight gain (BWG), feed consumption (FC), feed conversion ratio (FCR), carcass traits, blood parameters, and some physiological (rectum temperature, respiration rate) and health aspects (morbidity, mortality, and health risks %) were investigated. Rabbits of T1 showed the highest (P

Cecotrophy is a special behaviour of rabbits. Eating soft faeces can improve feed efficiency and maintain gut flora in rabbits. In our previous study, we found that fasting from soft faeces significantly reduced growth rate and total cholesterol (TC) in New Zealand white rabbits (NZW rabbits), thereby resulting in lower values for body weight and fat deposition in the soft faeces fasting group than in the control group. However, it has not been demonstrated whether cecotrophy by NZW rabbits can regulate lipid metabolism by changing the diversity of caecal microorganisms. In this study, thirty-six 28-day-old weaned NZW female rabbits were randomly divided into two groups (the soft faeces fasting group and the control group) and fed to 90 days. Rabbits in the experimental group were treated with an Elizabeth circle to prevent them from eating their soft faeces. Then, the caecal contents of three rabbits from the soft faeces fasting group and three rabbits from the control group were collected for metagenomic sequencing. We found that the abundance of Bacteroides increased, while Ruminococcus decreased, compared with the control group after fasting from soft faeces. Relative abundance was depressed for genes related to metabolic pathways such as ascorbate and aldarate metabolism, riboflavin metabolism and bile secretion. Moreover, there was a general correlation between variation in microbial diversity and fat deposition. Bacteroides affects body weight and TC by participating in the riboflavin metabolism pathway. By investigating the effect of cecotrophy on caecal microorganisms of rabbits, we identified the key microorganisms that regulate the rapid growth performance of NZW rabbits, which may provide useful reference for the future research and development of microecological preparations for NZW rabbits.

Species differences in developmental toxicity can be due to varying expression of xenobiotic transporters. Hence, knowledge on the ontogeny of these transporters, especially in human, rat and rabbit, is pivotal. Two superfamilies of transporters, the ATP-binding cassette (ABC) and the solute carrier (SLC) transporters, are well known for their role in the absorption, distribution and/or elimination of xenobiotics and endogenous substances. The aim of this study was to compare the expression levels of these xenobiotic transporters in liver, kidney and placenta of man, Wistar rat and New Zealand White rabbit during pre- and postnatal development. For this purpose, qPCR experiments were performed for rat and rabbit tissues and the gene expression profiles were compared with literature data from man, rat and rabbit. Data analysis showed large differences in transporter expression in development and between species. These results can be used to better understand developmental toxicity findings in non-clinical species and their relevance for man.

The aim of the present study was to explore the safety and effectiveness of radiofrequency ablation (RFA) of the ciliary body for the treatment of glaucoma. A glaucoma model was established in New Zealand white rabbits, which were then treated with RFA of the ciliary body, utilizing an XL‑1‑type RF meter developed by the Chinese PLA General Hospital. After treatment, general ocular investigation, including ocular pressure was carried out, the anterior chamber was imaged via ultrasound biomicroscopy, and the pathological changes were observed via hematoxylin and eosin (H&E) staining. It was determined that the glaucoma model was successfully established in the New Zealand white rabbit by inducing high intraocular pressure (IOP). After RFA treatment, ablation spots were observed but no clear anterior chamber reaction was found. The ablation group showed a steady and continuous decrease of IOP, which was significantly lower than the model group at days 3 and 7 (P

Physeal injuries can lead to bony repair tissue formation, known as a bony bar. This can result in growth arrest or angular deformity, which is devastating for children who have not yet reached their full height. Current clinical treatment involves resecting the bony bar and replacing it with a fat graft to prevent further bone formation and growth disturbance, but these treatments frequently fail to do so and require additional interventions. Novel treatments that could prevent bone formation but also regenerate the injured physeal cartilage and restore normal bone elongation are warranted. To test the efficacy of these treatments, animal models that emulate human physeal injury are necessary. The rabbit model of physeal injury quickly establishes a bony bar, which can then be resected to test new treatments. Although numerous rabbit models have been reported, they vary in terms of size and location of the injury, tools used to create the injury, and methods to assess the repair tissue, making comparisons between studies difficult. The study presented here provides a detailed method to create a rabbit model of proximal tibia physeal injury using a two-stage procedure. The first procedure involves unilateral removal of 25% of the physis in a 6-week-old New Zealand white rabbit. This consistently leads to a bony bar, significant limb length discrepancy, and angular deformity within 3 weeks. The second surgical procedure involves bony bar resection and treatment. In this study, we tested the implantation of a fat graft and a photopolymerizable hydrogel as a proof of concept that injectable materials could be delivered into this type of injury. At 8 weeks post-treatment, we measured limb length, tibial angle, and performed imaging and histology of the repair tissue. By providing a detailed, easy to reproduce methodology to perform the physeal injury and test novel treatments after bony bar resection, comparisons between studies can be made and facilitate translation of promising therapies toward clinical use. IMPACT STATEMENT: This study provides details to create a rabbit model of physeal injury that can facilitate comparisons between studies and test novel regenerative medicine approaches. Furthermore, this model mimics the human, clinical situation that requires a bony bar resection followed by treatment. In addition, identification of a suitable treatment can be seen in the correction of the growth deformity, allowing this model to facilitate the development of novel physeal cartilage regenerative medicine approaches.

PURPOSE: Females and males respond differently to a number of systemic viral infections. Differences between females and males with respect to the severity of keratitis caused by Gram-negative bacteria such as Serratia marcescens are less well established. METHODS: In this study we injected female and male New Zealand White rabbit corneas with a keratitis isolate of S. marcescens and evaluated the eyes after 48 hours for a number of clinical and microbiological parameters. RESULTS: No statistical differences in bacterial burden and corneal scores were recorded between female and male rabbits although there was a non-significant trend toward a higher frequency of female rabbits demonstrating hypopyons. CONCLUSIONS: This data suggests that for experimental bacterial keratitis studies involving Gram-negative rods, a single sex or mixed group of rabbit is sufficient for evaluating pathology and bacterial burdens. This will reduce the number of animals used for subsequent studies.

Cell line misidentification and contamination are major contributors to the reproducibility crisis in academic research. Authentication of cell lines provides assurances of the data generated; however, commercially available cells are often not subjected to rigorous identification testing. In this study, commercially available cell lines underwent testing to confirm cell identity and purity. The methods reported here outline the best practices for cell line authentication. Briefly, a commercially available primary rabbit aortic endothelial cell line was purchased for the intent of producing target proteins necessary for generating species-specific recombinant antibodies. These rabbit-specific antibodies would then be utilized for the development of in-house enzyme-linked immunosorbent assays (ELISA) to evaluate blood-based biomarkers of vascular injury after total-body irradiation. To authenticate the cell line, cell identity and purity were determined by single tandem repeat (STR) testing, flow cytometry, polymerase chain reaction (PCR), and cytochrome c oxidase subunit 1 (CO1) DNA Barcoding in-house and/or through commercial vendors. Fresh cells obtained from a New Zealand White rabbit (Charles River, Wilmington, DE) were used as a positive control. The results of STR and flow cytometry analyses indicated the cells were not contaminated with human or mouse cells, and that the cells were not of endothelial origin. PCR demonstrated that cells were also not of rabbit origin, which was further confirmed by a third-party vendor. An unopened vial of cells was submitted to another vendor for CO1 DNA Barcoding analysis, which identified the cells as being purely of bovine origin. Results revealed that despite purchase through a commercial vendor, the cell line marketed as primary rabbit aortic endothelial cells were of bovine origin. Purity analysis found cells were misidentified rather than contaminated. Further investigation to determine the cell type was not performed. The most cost-effective and efficient methodology for confirming cell line identity was found to be CO1 DNA Barcoding performed by a commercial vendor.

Rabbit haemorrhagic disease virus (RHDV) is associated with high morbidity and mortality in the European rabbit (Oryctolagus cuniculus). In 2010, a genetically distinct RHDV named RHDV2 emerged in Europe and spread to many other regions, including North America in 2016. Prior to this study it was unknown if eastern cottontails (ECT(s); Sylvilagus floridanus), one of the most common wild lagomorphs in the United States, were susceptible to RHDV2. In this study, 10 wild-caught ECTs and 10 New Zealand white rabbits (NZWR(s); O. cuniculus) were each inoculated orally with either RHDV (RHDVa/GI.1a; n = 5 per species) or RHDV2 (a recombinant GI.1bP-GI.2; n = 5 per species) and monitored for the development of disease. Three of the five ECTs that were infected with RHDV2 developed disease consistent with RHD and died at 4 and 6 days post-inoculation (DPI). The RHDV major capsid protein/antigen (VP60) was detected in the livers of three ECTs infected with RHDV2, but none was detected in the ECTs infected with RHDV. Additionally, RHD viral RNA was detected in the liver, spleen, intestine and blood of ECTs infected with RHDV2, but not in the ECTs infected with RHDV. RHD viral RNA was detected in urine, oral swabs and rectal swabs in at least two of five ECTs infected with RHDV2. One ECT inoculated with RHDV2 seroconverted and developed a high antibody titre by the end of the experimental period (21 DPI). ECTs inoculated with the classic RHDV did not seroconvert. In comparison, NZWRs inoculated with RHDV2 exhibited high mortality (five of five) at 2 DPI and four of five NZWRs inoculated with RHDV either died or were euthanized at 2 DPI indicating both of these viruses were highly pathogenic to this species. This experiment indicates that ECTs are susceptible to RHDV2 and can shed viral RNA, thereby suggesting this species could be involved in the epidemiology of this virus.

Aims Recently, a new defibrillation modality using nanosecond pulses was shown to be effective at much lower energies than conventional 10 millisecond monophasic shocks in ex vivo experiments. Here we compare the safety factors of 300 nanosecond and 10 millisecond shocks to assess the safety of nanosecond defibrillation. Methods and results The safety factor, i.e. the ratio of median effective doses (ED50) for electroporative damage and defibrillation, was assessed for nanosecond and conventional (millisecond) defibrillation shocks in Langendorff-perfused New Zealand white rabbit hearts. In order to allow for multiple shock applications in a single heart, a pair of needle electrodes was used to apply shocks of varying voltage. Propidium iodide (PI) staining at the surface of the heart showed that nanosecond shocks had a slightly lower safety factor (6.50) than millisecond shocks (8.69), p = 0.02; while PI staining cross-sections in the electrode plane showed no significant difference (5.38 for 300 ns shocks and 6.29 for 10 ms shocks, p = 0.22). Conclusions In Langendorff-perfused rabbit hearts, nanosecond defibrillation has a similar safety factor as millisecond defibrillation, between 5 and 9, suggesting that nanosecond defibrillation can be performed safely.

The selection and validation of stably expressed reference genes is key for accurately quantifying the mRNA abundance of genes under different treatments. In the rabbit model of fasting caecotrophy, reports about the selection of stable reference genes are not available. This study aims to screen suitable reference genes in different tissues (including uterus, cecum, and liver) of rabbits between control and fasting caecotrophy groups. RT-qPCR was used to analyze the expression levels of eight commonly used reference genes (including GAPDH, 18S rRNA, B2M, CYP, HPRT1, β-actin, H2afz, Ywhaz), and RefFinder (including geNorm, NormFinder, and BestKeeper) was used to analyze the expression stability of these reference genes. Our results showed that the most stable reference genes were different in different tissues and treatments. In the control and fasting caecotrophy groups, CYP, GAPDH and HPRT1 were proven to be the top stable reference genes in the uterus, cecum, and liver tissues, respectively. GAPDH and Ywhaz were proven to be the top two stable reference genes among uterus, cecum, and liver in both control and fasting caecotrophy groups. Our results indicated that the combined analysis of three or more reference genes (GAPDH, HPRT1, and Ywhaz) are recommended to be used for RT-qPCR normalization in the rabbit model of fasting caecotrophy, and that GAPDH is a better choice than the other reference genes for normalizing the relative expression of target genes in different tissues of fasting caecotrophy rabbits.

Background and objectives Widespread applications of supercontinuum (SC) source lead to the possibility of ocular damages. However, the corneal damage effects induced by SC have not been explored before. The objectives of this study are to determine the rabbit corneal injury threshold for SC radiation and to examine whether the existing safety guidelines and standards are suitable for the hazard evaluation of this new kind of light source. Study design/materials and methods A series of experiments was conducted in the New Zealand white rabbit model to determine the corneal damage thresholds induced by a 770-2,500 nm SC source, with a corneal 1/e beam diameter of 0.37 mm. Through slit-lamp biomicroscope, optical coherence tomography (OCT), and histopathology the corneal damage characteristics at the threshold level were revealed. By employing the action spectra determined through the analysis of safety guidelines and standards, the damage thresholds for SC source could be compared with the corresponding exposure limits. Results The determined damage thresholds given in terms of the peak radiant exposure for exposure durations of 2.0 and 10.0 seconds were 2.1 × 103 and 7.4 × 103 J/cm2 , respectively. At threshold level, corneal damages involved the epithelium and the shallower stroma, and no obvious changes could be found in the deep stroma, Descemet's membrane, and endothelium. Conclusions The exposure limits for the anterior parts of the eye in the wavelength range of 700-1,200 nm are overly conservative. The obtained results contribute to the knowledge base for the hazard evaluation of SC source. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Species-dependent differences in relative incidence of spontaneous variations and malformations should be considered in the assessment of the translational value of reproductive and developmental safety assessments. The objective of this evaluation was to compare litter parameters and the frequency of external, visceral, and skeletal malformations and variations across species in the Sprague-Dawley rat, New Zealand White rabbit, and Göttingen minipig and to determine whether notable differences exist. Pregnant female rats (n = 824), rabbits (n = 540), and minipigs (n = 70) from vehicle control groups were included in the analysis, equating to 10,749 rat, 5,073 rabbit, and 378 pig fetuses collected at term by cesarean delivery. Preimplantation loss was more frequent than postimplantation loss in the rat and rabbit, whereas the opposite was observed in the minipig. Several external and visceral malformations and variations such as domed head, bent tail, abdominal edema, and anal atresia were observed in all 3 species. Visceral malformations of the heart and major blood vessels were remarkably more frequent in the minipig and rabbit, respectively; ventricular and atrium septum defects were observed in 1.9% and 2.1%, respectively, for the minipig fetuses, whereas they were observed in equal or less than 0.02% among the rat and rabbit fetuses evaluated in this study. Understanding species-dependent differences in spontaneous variations and malformations can be useful for the interpretation of embryo–fetal development study results. The current analysis identified relevant differences between commonly used species in reproductive toxicology with potential implications for data assessment.

Emergent stroke is mostly evaluated using hospital based imaging. Quick imaging allows for rapid administration of IV thrombolysis and outcome improvement. Microwave imaging (MI) is an emerging portable imaging modality. Iron oxide nanoparticles are known to interact with microwave frequency electromagnetic radiation. In this manuscript, we provide proof of concept for a novel iron oxide nanoparticle enhanced microwave imaging device for differentiating emergent ischemic stroke from hemorrhagic stroke. A MI device was constructed. Attenuation of the microwave signal transmitted with or without iron oxide nanoparticles was measured over a 1–2 GHz frequency range in a silicone brain phantom, in New Zealand white rabbits, and in a human. Observed differences in signal attenuation were used to reconstruct an image following induction of a left sided anterior circulation stroke in a New Zealand white rabbit. An increase in microwave signal attenuation exists across a frequency range of 1.3–2 GHz when iron oxide nanoparticles are introduced into a silicone phantom model, in New Zealand white rabbits, and in a human volunteer. Using this increase in signal attenuation following nanoparticle administration, we localize induced ischemia in a New Zealand white rabbit. To the best of out knowledge, we provide the first evidence that superparamagnetic Iron oxide nanoparticles may be used as contrast in the setting of MI. Our data suggest infusion of intravenous iron oxide nanoparticles with follow on microwave imaging may ultimately allow for more timely administration of thrombolytic mediation in the setting of acute ischemic stroke.

This study aimed to investigate the role of Gelam honey (GH) in accelerating reepithelialization of corneal abrasion. Corneal epithelial cells (CEC) isolated from New Zealand white rabbit corneas, were cultured and circular-shaped wounds were created onto them, representing the corneal abrasion model. These wounds were treated with basal (BM) and cornea media (CM) supplemented with GH. The percentage of wound closure was measured on day 0, 3, and 5. Expressions of cytokeratin 3 (CK3), cluster of differentiation 44 (CD 44), and connexin 43 (Cx43) were analyzed via qRT-PCR and immunocytochemistry. The results showed CEC cultured in GH-enriched media reepithelialized faster compared to control. Corneal abrasion treated with CM supplemented with GH closed completely on day 5. CK3, CD44, and Cx43 expressions correspond to the stages of reepithelialization. In conclusion, GH promotes the healing of the ex vivo corneal abrasion model. Further explorations of its potential as adjuvant therapy in treating corneal injuries are needed. PRACTICAL APPLICATIONS: Honey has been reported to have many medicinal properties including antibacterial, anti-inflammatory, and the ability to promote skin wound healing. However, the effects of honey on corneal wound healing have not been fully elucidated. In the present study, we aimed to determine the effects of Gelam honey (GH), well-known local honey obtained from the beehive of Gelam trees (Melaleuca spp.), on the ex vivo corneal abrasion model via cell migration study and analysis of genes and proteins during corneal epithelial wound healing. GH has proven to have accelerated effects on the corneal epithelial cell migration during the closure of the ex vivo corneal abrasion wound model. The expressions of the genes and proteins of the corneal epithelial wound healing markers were in accordance with the stages of healing. Therefore, GH has the potential to be developed as adjuvant therapy in the form of GH-based eye drop in treating corneal injuries.

Purpose Wound healing after Ahmed glaucoma valve (AGV) implantation often entails fibrosis as a foreign body reaction to the silicone plate. Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) forms an antifouling surface that inhibits fibrosis during wound healing. In this study, we aimed to compare the effects of the implantation of AGV coated with PMPC (wPMPC) versus AGV without PMPC (woPMPC) in rabbits. Methods Six New Zealand White rabbit does underwent AGV implantation in both eyes. For each rabbit, one eye was randomly selected for implantation of AGV wPMPC and a conventional AGV (woPMPC) was implanted in the contralateral eye. Gross conjunctival vascularity was compared between the two groups at the first, second, and fourth weeks after surgery. The eyes were enucleated in four weeks and subjected to staining with hematoxylin and eosin and Masson’s trichrome stain. The fibrosis and inflammation status among the eye samples were compared by measuring the thickness of the fibrotic walls and counting the number of chronic inflammatory cells around the AGV. Counting of inflammatory cells and measuring fibrotic wall thickness were done in a blinded method to eliminate observer bias. Statistical analysis was performed using the Mann-Whitney U test. Results Gross and histological examinations revealed no toxic effects of PMPC. There were no apparent differences in overall conjunctival vascularity between the two groups at weeks 1, 2, and 4 after surgery. The average inflammatory cell counts were 14.3 ± 5.8 per slide and 27.3 ± 8.6 per slide in the wPMPC and woPMPC groups, respectively (p = 0.037). The average thicknesses of the fibrotic wall were 57.9 ± 11.3 μm and 81.5 ± 21.3 μm in the wPMPC and woPMPC groups, respectively (p = 0.025). Conclusion Compared to the woPMPC group, the number of inflammatory cells and fibrosis were significantly decreased in the wPMPC group.

OBJECTIVES This study's objective was to identify and compare the localization of Aquaporin (AQP) 1, 4, 7, Na+/K + -ATPase, E-cadherin, zona occludin (ZO)-1, and occludin in human and rabbit vocal folds (VF)s to inform the design of future studies to explore the function of these proteins in the regulation of VF homeostasis. METHODS Four human larynges and five New Zealand white rabbit larynges were used. Samples were immunolabeled for primary antibodies against AQP1, AQP4, AQP7, the alpha subunit of Na+/K + -ATPase, E-cadherin, and ZO-1 and occludin and then captured digitally using a Nikon Eclipse 90i microscope and Hamamatsu C10600 Camera. Two raters familiar with human and rabbit VF histology identified positive labeling in tissue structures, including the apical epithelium, basal epithelium/basement membrane, and lamina propria (LP). RESULTS Samples from both species showed positive labeling for AQP1 in the basal epithelium/basement membrane, superficial LP, and deep/intermediate LP. Aquaporin 4, Aquaporin 7, Na+/K + -ATPase, and E-cadherin were primarily localized to the epithelium of both species. Zona occludin-1 was primarily localized apical epithelium and the superficial LP of both species. Occludin was primarily present in the apical epithelium in rabbit samples but not human. CONCLUSION These data provide evidence of the presence of key ion transport channels and cell adhesion proteins in human and rabbit VFs. Aquaporin 1, 4, 7, Na+/K + -ATPase, E-cadherin, and ZO-1 were similarly localized in both species. These findings will be useful to investigators interested in the exploration of VF homeostasis and barrier integrity in future studies. LEVEL OF EVIDENCE N/A Laryngoscope, 131:E1265-E1271, 2021.

Well-controlled ionizing radiation injury animal models for testing medical countermeasure efficacy require robust radiation physics and dosimetry to ensure accuracy of dose-delivery and reproducibility of the radiation dose-response relationship. The objective of this study was to establish a simple, convenient, robust and accurate technique for validating total body irradiation (TBI) exposure of the New Zealand White rabbit. We use radiotherapy techniques such as computed tomography simulation and a 3 D-conformal radiation therapy treatment planning system (TPS) on three animals to comprehensively design and preplan a TBI technique for rabbits. We evaluate the requirement for bolus, treatment geometry, bilateral vs anterior-posterior treatment delivery, the agreement between monitor units calculated using the TPS vs a traditional hand calculation to the mid-plane, and resulting individual organ doses. The optimal technique irradiates animals on the left-decubitus position using two isocentric bilateral parallel-opposed 6 MV x-ray beams. Placement of a 5 mm bolus and 8.5 mm beam spoiler was shown to increase the dose to within ���5 mm of the surface, improving dose homogeneity throughout the body of the rabbit. A simple hand calculation formalism, dependent only on mid-abdominal separation, could be used to calculate the number of monitor units (MUs) required to accurately deliver the prescribed dose to the animal. For the representative animal, the total body volume receiving > 95% of the dose, V95% > 99%, V100% > 95%, and V107% 107% of the prescribed dose was mainly within the limbs, head, and around the lungs of the animal, where the smaller animal width reduces the x-ray attenuation. Individual organs were contoured by an experienced dosimetrist, and each received doses within 95���107% of the intended dose, with mean values ���104%. Only the bronchus showed a maximal dose >107% (113%) due to the decreased attenuation of the lungs. To validate the technique, twenty animals were irradiated with four optically-stimulated luminescence dosimeters (OSLDs) placed on the surface of each animal (two on each side in the center of the radiation beam). The average dose over all animals was within

Animal models that accurately reflect human responses to radiation injury are needed for advanced mechanistic investigation and development of effective therapeutics. The rabbit is an established animal model accepted by the FDA for studies of cardiovascular disease, lipid metabolism, the development of anticoagulants, testing of bone implants, and the development of treatments for infectious diseases such as HIV. The purpose of this study was to investigate the New Zealand White (NZW) Rabbit model as a model of acute radiation exposure because of its established similarity to human vascular, immune, and coagulation responses. Two sequential studies were performed in a total of 81 male NZW rabbits, 16���20 weeks of age. All animals underwent clinical observations and peripheral blood analyses following a single dose of 0, 6, 7, 8, 8.5, 9, or 10 Gy of total body irradiation via a 6 MV Linear accelerator photon source on day 0. Animals were treated with timed release fentanyl patch (days 0���30), subcutaneous hydration (day 1, Study 2 only), and oral sulfamethoxazole/trimethoprim 30 mg/kg once daily (days 3���30) and were followed for 30 days or to time of mortality. Study 1 revealed the estimated LD30, ���50, ���70, and ���90 with 95% confidence intervals (CI) at 30 days to be 6.7 (CI: 5.9���7.4), 7.3 (CI: 6.7���7.8), 7.9 (CI: 7.3���8.4), and 8.8 (CI: 7.9���9.7) Gy, respectively. In study 2, a survey of blood coagulation and biochemical parameters were performed over time and necropsy. Complete blood counts taken from animals exposed to 7, 8, or 10 Gy, demonstrated dose-dependent depletion of lymphocytes, neutrophils, and platelets. Platelet counts recovered to baseline levels in survivors by day 30, whereas lymphocyte and neutrophil counts did not. Decedent animals demonstrated grade 3 or 4 neutropenia and lymphopenia at time of death; 64% of the decedents experienced a 30% or greater drop in hematocrit. Decedent animals demonstrated more than 100% increases from serum baseline levels of blood urea nitrogen, creatinine, aspartate aminotransferase, and triglyceride levels at the time of death whereas survivors on average demonstrated modest or no elevation. This NZW rabbit model demonstrates dose-dependent depletion of hematopoietic parameters. The LD50/30 of 7.8 Gy (95% CI: 6.6���8.4) with supportive care appears to be close to the ranges reported for rhesus macaques (5.25���7.44 Gy) and humans (6���8 Gy) with supportive care. These findings support the utility of the NZW rabbit model for further mechanistic investigation of acute radiation exposure and medical countermeasure testing.

The hemorrhagic syndrome is a major cause of morbidity and mortality associated with the acute radiation syndrome (ARS). We previously characterized the dose-response relationship for total body irradiation (TBI)-induced ARS in the New Zealand White (NZW) rabbit. Thrombocytopenia, hemorrhage, and anemia were strongly associated with morbidity/mortality during the first three weeks post-TBI. The objective of the current study was to further characterize the natural history of thrombocytopenia, hemostatic dysfunction and hemorrhage in the rabbit model at a TBI dose range to induce ARS.Fifty male NZW rabbits were randomized to receive 7.0 or 7.5 Gy of 6 MV-derived TBI. Sham-irradiated controls (Findings in this study include severe neutropenia during the first week post-TBI followed by thrombocytopenia and severe acute anemia with petechial hemorrhages of the skin and hemorrhage of the vital organs during the second to third weeks post-TBI. Abnormalities in whole blood viscoelastometry were observed concurrent with thrombocytopenia and hemorrhage. Antithrombin activity was significantly elevated in animals after exposure to 7.5 Gy, but not 7.0 Gy TBI.The hemorrhagic syndrome in the rabbit model of TBI recapitulates the pathogenesis described in humans following accidental or deliberate exposures. The rabbit may present an alternative to the rodent model as a small animal species for characterization of the full spectrum of multiorgan injury following TBI and early testing of promising medical countermeasures.

Purpose To evaluate the safety and efficacy of an experimental dexamethasone-eluting contact lens (DCL) for the prevention of postphotorefractive keratectomy (PRK) corneal haze in a New Zealand White (NZW) rabbit model. Methods Both eyes of 29 NZW rabbits underwent PRK. The rabbits were randomized to one of the 5 study arms for 4 weeks: tarsorrhaphy only, tarsorrhaphy and bandage contact lens (BCL) replaced weekly, tarsorrhaphy and BCL for 1 week plus topical 0.1% dexamethasone ophthalmic solution (drops) for 4 weeks, tarsorrhaphy and BCL replaced weekly plus topical dexamethasone for 4 weeks, and tarsorrhaphy and DCL changed weekly for 4 weeks. Each week for 4 consecutive weeks postoperatively, the tarsorrhaphies were opened, the eyes underwent evaluation and imaging, and the tarsorrhaphies were replaced. Contact lenses were cultured on removal. Central corneal haze was assessed weekly with corneal densitometry. After 4 weeks, the animals were killed, and the eyes were enucleated for histopathologic analysis. Results The tarsorrhaphy only group displayed more haze with a greater change in optical densitometry from pre-op compared with the other treatment groups. There was no difference between the DCL group and the groups receiving a BCL and dexamethasone drops in densitometry or histopathology. No NZW rabbits developed clinical signs of infection, and cultures from DCLs and BCLs grew similar organisms. Conclusions In the post-PRK rabbit model, DCLs worn weekly for 4 weeks were safe and as effective at preventing corneal haze as 0.1% dexamethasone drops applied 4 times a day for 4 weeks.

Anterior urethral reconstruction is still a challenging clinical task, and tissue engineering technology offers new options for anterior urethroplasty. In this work, we evaluated an extracellular matrix (ECM) mimicking scaffold for anterior urethral reconstruction in a New Zealand white rabbit model. After the creation of a urethral defect, the ECM-mimicking scaffold was applied in six rabbits, and small intestinal submucosa (SIS) was used in three rabbits. The outcomes of urethrography and histological analysis were evaluated six months postoperatively. A larger urethral diameter was observed in the ECM-mimicking scaffolds (3.01 ± 0.12 mm) than in the SIS grafts (0.95 ± 0.07 mm). Urethral fistulae and stenosis were observed in the SIS grafts. Urothelial and smooth muscle cells were observed in all rabbits, but the ECM-mimicking scaffold showed better performance. The ECM-mimicking scaffold may be an effective clinical treatment option for congenital and acquired urethral pathologies.

BackgroundThe New Zealand White rabbit (NZWR) is the first small-animal experimental model of intra-arterial chemotherapy (IAC) for retinoblastoma treatment. The NZWR has dual ophthalmic arteries (OA): the external OA (EOA) arises from the external carotid artery and the internal OA (IOA) from the internal carotid artery. We describe the technique that we have refined for OA catheterization in rabbits, and describe the angioanatomical variations in the OA supply to the NZWR eye and implications for IAC delivery, which were identified as part of a larger project exploring IAC effects in a rabbit retinoblastoma model.MethodsWe developed techniques to perform angiography of the external and internal carotid arteries and superselective angiography of the EOA and IOA in NZWR using transfemoral access and a microwire/microcatheter system. EOA and IOA supply to the eye was determined angiographically and recorded before selective OA catheterization and angiography.Results114 rabbits underwent carotid angiographic evaluation and OA catheterization (161 total eyes evaluated, 112 right, 49 left). Most eyes had a single dominant arterial supply; either IOA or EOA. EOA was dominant in 73% (118/161), and IOA was dominant in 17% (27/161). Co-dominant supply was seen in 10% (16/161). Of the rabbits with bilateral OA catheterization, 25/47 (53%) had bilateral dominant EOA.ConclusionSuccessful catheterization of the OA in the NZWR can be readily accomplished with nuanced technique. The external OA is the dominant arterial supply in the majority of NZWR eyes. These findings allow for successful reproduction of OA catheterization studies of IAC for retinoblastoma in NZWR.

Objective: Spinal tuberculosis (ST) refers to tuberculosis resulted from infections of Mycobacterium tuberculosis (Mtb) in the spinal cord. Hesperidin methyl chalcone (HMC) is a flavonoid derivative from citrus fruits with anti-inflammatory properties. We aimed to investigate the efficacy of HMC in treating ST in New Zealand white rabbit model. Design and Setting: Rabbits were infected in the sixth lumbar vertebral bodies with or without Mtb strain H37Rv followed by treatments with HMC. Outcome Measures: 10 weeks post treatments, the adjacent vertebral tissues were examined by hematoxylin–eosin staining. The expression levels of transcription factor κB (NF-κB) p65 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in lymphocytes were determined using reverse transcription quantitative real-time PCR (RT-qPCR), Western blot and enzyme-linked immunosorbent assays (ELISA). The serum levels of interleukin (IL)-2, IL-4, IL-10 as well as interferon (IFN)-γ were also assessed using ELISA. Western blot was used to determine the effects of HMC on the phosphorylation of IKKα/β, p65, and IκBα in the signal transduction of NF-κB pathways. Results: HMC significantly attenuated the granulation in adjacent vertebral bone tissues. The expression of p65, IL-4, IL-10, and MCP-1 was reduced. The NF-κB pathway was suppressed, in which the phosphorylation of IκBα, IKKα/β, and p65 was inhibited whereas the relative level of IκBα was increased. Conclusion: HMC could serve as a therapeutic option to effectively inhibit granulomas formation through downregulation of MCP-1, IL-4, IL-10, and NF-κB in the treatment of ST.

Mg-based stent is a promising candidate of the next generation fully degradable vascular stents. The latest progress includes the CE approval of the Magmaris ® WE43 based drug eluting stent. However, so far, the long term (more than 1 year implantation) in vivo degradation and the physiological effects caused by the degradation products were still unclear. In this study, a 20 month observation was carried out after the bare Mg-Nd-Zn-Zr (abbr. JDBM) stent prototype was implanted into the common carotid artery of New Zealand white rabbit in order to evaluate its safety, efficacy and especially degradation behavior. The degradation of the main second phase Mg12Nd was also studied. Results showed that the bare JDBM stent had good safety and efficacy with a complete re-endothelialization within 28 days. The JDBM stent struts were mostly replaced in situ by degradation products in 4 month. The important finding was that the volume and Ca concentration of the degradation products decreased in the long term, eliminating the clinicians’ concern of possible vessel calcification. In addition, the alloying elements Mg and Zn in the stent could be safely metabolized as continuous enrichment in any of the main organs were not detected although Nd and Zr showed an abrupt increase in spleen and liver after 1 month implantation. Collectively, the long term in vivo results showed the rapid re-endothelialization of JDBM stent and the long term safety of the degradation products, indicating its great potential as the backbone of the fully degradable vascular stent. Statement of significance Mg-based stent is a promising candidate of the next generation fully degradable stents, especially after the recent market launch of one of its kind (Magmaris). However the fundamental question about the long term degradation and metabolic mechanism of Mg-based stent and its degradation products remain unanswered. We implanted our patented Mg-Nd-Zn-Zr bare stent into the common carotid artery of rabbits and conducted a 20 months observation. We found that the Ca containing degradation products could be further degraded in vivo. All the alloying elements showed no continuous enrichment in the main organs of rabbits. These findings eliminate the clinicians’ concern of possible vessel calcification and element enrichment after the implantation of Mg alloy based stents to some extent.

Purpose The purpose is to target model drug particles to the posterior region of the suprachoroidal space (SCS) of the eye controlled via pushing by hydrogel swelling. Methods A particle formulation containing 1% hyaluronic acid (HA) with fluorescent polymer particles and a hydrogel formulation containing 4% HA were introduced in a single syringe as two layers without mixing, and injected sequentially into the SCS of the rabbit eye ex vivo and in vivo using a microneedle. Distribution of particles in the eye was determined by microscopy. Results During injection, the particle formulation was pushed toward the middle of the SCS by the viscous hydrogel formulation, but less than 12% of particles reached the posterior SCS. After injection, the particle formulation was pushed further toward the macula and optic nerve in the posterior SCS by hydrogel swelling and spreading. Heating the eye to 37°C, or injecting in vivo decreased viscosity and mechanical strength of the hydrogel, thereby allowing it to swell and flow further in the SCS. A high salt concentration (9% NaCl) in the hydrogel formulation further increased hydrogel swelling due to osmotic flow into the hydrogel. In this way, up to 76% of particles were delivered to the posterior SCS from an injection made near the limbus. Conclusions This study shows that model drug particles can be targeted to the posterior SCS by HA hydrogel swelling and pushing without particle functionalization or administering external driving forces.

Aims Reliable defibrillation with reduced energy deposition has long been the focus of defibrillation research. We studied the efficacy of single shocks of 300 ns duration in defibrillating rabbit hearts as well as the tissue damage they may cause. Methods and results New Zealand white rabbit hearts were Langendorff-perfused and two planar electrodes were placed on either side of the heart. Shocks of 300 ns duration and 0.3-3 kV amplitude were generated with a transmission line generator. Single nanosecond shocks consistently induced waves of electrical activation, with a stimulation threshold of 0.9 kV (over 3 cm) and consistent activation for shock amplitudes of 1.2 kV or higher (9/9 successful attempts). We induced fibrillation (35 episodes in 12 hearts) and found that single shock nanosecond-defibrillation could consistently be achieved, with a defibrillation threshold of 2.3-2.4 kV (over 3 cm), and consistent success at 3 kV (11/11 successful attempts). Shocks uniformly depolarized the tissue, and the threshold energy needed for nanosecond defibrillation was almost an order of magnitude lower than the energy needed for defibrillation with a monophasic 10 ms shock delivered with the same electrode configuration. For the parameters studied here, nanosecond defibrillation caused no baseline shift of the transmembrane potential (that could be indicative of electroporative damage), no changes in action potential duration, and only a brief change of diastolic interval, for one beat after the shock was delivered. Histological staining with tetrazolium chloride and propidium iodide showed that effective defibrillation was not associated with tissue death or with detectable electroporation anywhere in the heart (six hearts). Conclusion Nanosecond-defibrillation is a promising technology that may allow clinical defibrillation with profoundly reduced energies.

Background/Aims: This study aimed to explore the role of TGF-β in tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction using bone marrow-derived mesenchymal stem cells (BMSCs) through the TGF-β/MAPK signaling pathway in a New Zealand white rabbit model. Methods: A total of 72 healthy male New Zealand white rabbits were selected for these experiments. Flow cytometry and immunofluorescence were used to detect the expression of BMSC surface markers, and qRT-PCR was performed to detect TGF-β mRNA expression. The ACL reconstruction model was established with autografts. The rabbits were randomly divided into the following groups: inhibition of TGF-β (inhibition), over-expression of TGF-β (over-expression), empty vector and untreated (n = 18 per group). Hematoxylineosin (HE) staining, toluidine blue staining and Masson trichrome staining were conducted to observe any chondrocyte-like cell growth, and biomechanical tests were used to calculate the maximum load and rigidity. Three-dimensional CT imaging and Western blotting were applied to detect changes in bone tunnel size and bone density and the expression levels of TGF-β/MAPK signaling pathway-related proteins, respectively. Results: CD90 and CD44 were positively expressed, while CD11b was not detected. Compared with the empty vector and untreated groups, TGF-β mRNA expression was significantly decreased in the inhibition group but increased in the over-expression group; the latter group had a larger number of fibroblasts, a tighter tendon-bone interface, an increased number of chondrocyte-like cells and fibrochondrocytes, and more collagen fibers than the inhibition, empty vector and untreated groups. Compared with the empty vector and untreated groups, the maximum load and rigidity; the CT values of bone tunnel and bone tunnel margin; and the protein expression levels of TGF-β, p-ERK1/2, p-p38, p-JNK, c-jun and c-myc were significantly down-regulated in the inhibition group but up-regulated in the over-expression group. Conclusion: Our study indicated that up-regulating TGF-β expression in BMSCs from New Zealand white rabbits could promote tendon-to-bone healing after ACL reconstruction by regulating the TGF-β/MAPK signaling pathway.

IV injection of dodecafluoropentane emulsion (DDFPe) increases oxygen transportation and reduces brain infarct volume in a rabbit stroke model. Tissue distribution of the parent perfluorocarbon dodecafluoropentane (DDFP) is unknown but is critical to understanding the mechanism by which DDFPe is effective in treating ischemia and for determining safe dosing. Previous studies showed a DDFP blood half-life of2 min yet therapeutic effects lasted90 min after injection. We describe DDFP distribution in brain, kidney, liver, spleen, and lung following nine dosing regimens in New Zealand White (NZW) rabbits. Single and multi-dose schedules were administered to NZW rabbits (n = 27). A single DDFPe dose (0.6 ml/kg) group was sacrificed 2 min after dosing and eight multi-dose groups (4 doses of 0.3 or 0.6 ml/kg and 15 doses of 0.1, 0.3, or 0.6) were sacrificed 90 min after final injections. Tissues were flash frozen and analyzed with headspace sampling/GC-MS. DDFP brain concentration increased with increasing dose in the 15 dose groups (4.70, 8.34, and 14.3 μg/g) and indicative of linear pharmacokinetics within this dose range. The DDFP lung concentration was not reflective of increasing dose or dose frequency. The total clearance of DDFP was consistent with previous reports showing 98% of DDFP is cleared within 2 h of administration.

A Comparison of the Direct Cerebral Vasodilating Potencies of Halothane and Isoflurane in the New Zealand White Rabbit. By Drummond JC, Todd MM, Scheller MS, and Shapiro HM. Anesthesiology 1986; 65:462–7. Reprinted with permission. Halothane is commonly viewed as a more potent cerebral vasodilator than isoflurane. It was speculated that the lesser vasodilation caused by isoflurane might be the result of the greater reduction in cerebral metabolic rate (CMR) that it causes, and that the relative vasodilating potencies of halothane and isoflurane would be similar if the two agents were administered in a situation that precluded volatile-agent–induced depression of CMR. To test this hypothesis, cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) were measured in two groups of rabbits before and after the administration of 0.75 MAC halothane or isoflurane. One group received a background anesthetic of morphine and N2O, which resulted in an initial CMRO2 of 3.21 ± 0.17 (SEM) ml · 100 g–1 · min–1; second group received a background anesthetic of high-dose pentobarbital, which resulted in an initial CMRO2 of 1.76 ± 0.16 ml · 100 g–1 · min–1. In rabbits receiving a background of morphine sulfate/N2O, halothane resulted in a significantly greater CBF (65 ± 10 ml · 100 g–1 · min–1) than did isoflurane (40 ± 5 ml · 100 g–1 · min–1). Both agents caused a reduction in CMRO2, but CMRO2 was significantly less during isoflurane administration. By contrast, with a background of pentobarbital anesthesia, CBF increased by significant and similar amounts with both halothane and isoflurane. With halothane, CBF increased from 22 ± 2 ml · 100 g–1 · min–1 in the control stage to 39 ± 3, and with isoflurane from 24 ± to 38 ± 2 ml · 100 g–1 · min–1. CMRO2 was not depressed further by either halothane or isoflurane. These results suggest that the relative effects of halothane and isoflurane on CBF are dependent on the CMR present prior to their administration. When the preexistent CMR is not markedly depressed, isoflurane decreases CMR and causes less cerebral vasodilation than does halothane. When initial CMR is depressed, halothane and isoflurane have similar vasodilating potencies.

This study was conducted to evaluate the changing concentrations of metabolic hormones and metabolites in pregnant (P) and pseudopregnant (PP) rabbit does. Twenty-five New Zealand White rabbit does were submitted to artificial insemination (AI) and then classified as P (n = 15) or PP (n = 10). Blood samples were collected weekly until day 32 post AI. During pregnancy, leptin concentrations were greater on Days 14 and 21 (P< 0.05), while insulin was greater on days 21 and 32 post AI (P< 0.05) compared to PP does. The triiodothyronine/thyroxine (T3/T4) ratio was greater in the first and last week (P< 0.001); whereas, cortisol concentrations were greater in the last week of pregnancy and after parturition (P< 0.01) compared with that of PP does. Non-esterified fatty acids (NEFA) concentrations increased from day 7 until day 32 post AI (P< 0.05). Glucose concentrations were unchanged throughout pregnancy although concentrations were positively associated with litter size. These results indicate concentrations of hormones and metabolites change during pregnancy to ensure energy requirements are met for both the foetuses and the maternal tissues. Physiological hyperleptinemia, hyperinsulinemia, and changes in cortisol as well as thyroid hormones indicate there is an adaptation of metabolic functions induced by pregnancy. These adaptations could be mediated by gonadal steroids because changes mainly occur in the second half of pregnancy when the profile of the sex hormones differs between P and PP does.

Scar forming wounds are often characterized by higher levels of vascularity than non-scarring wounds and normal skin, and inhibition of angiogenesis has been shown to inhibit scar formation in some model systems. The rabbit ear hypertrophic scar (HS) model has been widely used to study the mechanisms that underlie the development of HS as well as the effectiveness of various treatments. Although the rabbit ear HS model is well characterized in terms of scar formation, the rate and level of angiogenesis has not been investigated in this model, and the cause-effect relationship between angiogenesis and rabbit HSs has not been examined. In the current study, full-thickness excisional wounds were created on the ventral side of New Zealand White rabbit ears to induce HS formation, and the dynamic pattern of angiogenesis and the expression of angiogenic regulatory factors were examined over time. Blood vessel density was found to peak at 2.7% on day 14 post-wounding, decreasing to 1.7% by day 28. mRNA levels of the proangiogenic factor VEGF-A peaked at day 14, while the expression of the antiangiogenic factors pigment epithelium-derived factor (PEDF) and thrombospondin 1 (TSP1) peaked at day 28 post-wounding. To examine whether inhibition of angiogenesis influences HS formation in this model, wounds were treated with exogenous soluble antiangiogenic agents including recombinant PEDF (rPEDF) and a functional PEDF peptide (PEDF-335). rPEDF and PEDF-335 were administered intradermally from day 4 post-wounding every 3 days until day 19. Intradermal injection of rPEDF or PEDF-335 both led to decreased angiogenesis and decreased collagen deposition at the wound site. The results support the utility of antiangiogenic therapies, including rPEDF/PEDF-335, as a potential new strategy for the prevention or treatment of HSs.

Purpose: The purpose if this study was to develop a rabbit model of total body irradiation (TBI) -induced thrombocytopenia and coagulopathy across the dose-range which induces the hematopoietic subsyndrome of the acute radiation syndrome (H-ARS). Methods: Twenty male New Zealand White rabbits were assigned to arms to receive 6-MV of TBI at a dose of 6.5, 7.5, 8.5 or 9.5 Gy. Animals were treated with moderate levels of supportive care including buprenorphine for pain management, antibiotics, antipyretics for rectal body temperature >104.8 ��F, and fluids for signs of dehydration. Animals were closelyfollowed for up to 45 days after TBI for signs of major morbidity/mortality. Hematology and serum chemistry parameters were routinely monitored. Hemostasis parameters were analyzed prior to TBI, 2 and 6 hours post-TBI, and at the time of euthanasia. Results: Animals developed the characteristic signs and symptoms of H-ARS during the first-week post TBI. Animals became thrombocytopenic with signs of severe acute anemia during the second week post TBI. Moribund animals presented with petechia and ecchymosis of the skin and generalized internal hemorrhage. Multiorgan dysfunction characterized by bone marrow failure, gastric ileus, acute renal toxicity, and liver abnormalities were common. Severe abnormalities in coagulation parameters were observed. Conclusions: The presentation of bone marrow failure and multiorogan injury associated with ARS in the New Zealand White rabbit model is consistent with that described in the canine, swine, non-human primate, and in humans. The hemorrhagic syndrome associated with the ARS in rabbits is characterized by thrombocytopenia and hemostasis dysfunction, which appear to underlie the development of multiorgan dysfunction following TBI to rabbits. Taken together, the rabbit recapitulates the pathogenesis of ARS in humans, and may present an alternative small animal model for medical countermeasure pilot efficacy screening, dose-finding and schedule optimization studies prior to moving into large animal models of TBI-induced ARS.

We describe the in vitro and in vivo evaluation of a subcutaneous reservoir implant delivering tenofovir alafenamide hemifumarate (TAF) for the prevention of HIV infection. These long-acting reservoir implants were able to deliver antiretroviral drug for over 90 days in vitro and in vivo. We evaluated the implants for implantation site histopathology and pharmacokinetics in plasma and tissues for up to 12 weeks in New Zealand White rabbit and rhesus macaque models., We describe the in vitro and in vivo evaluation of a subcutaneous reservoir implant delivering tenofovir alafenamide hemifumarate (TAF) for the prevention of HIV infection. These long-acting reservoir implants were able to deliver antiretroviral drug for over 90 days in vitro and in vivo. We evaluated the implants for implantation site histopathology and pharmacokinetics in plasma and tissues for up to 12 weeks in New Zealand White rabbit and rhesus macaque models. A dose-ranging study in rabbits demonstrated dose-dependent pharmacokinetics and local inflammation up to severe necrosis around the active implants. The matched placebos showed normal wound healing and fibrous tissue encapsulation of the implant. We designed a second implant with a lower release rate and flux of TAF and achieved a median cellular level of tenofovir diphosphate of 42 fmol per 106 rhesus macaque peripheral blood mononuclear cells at a TAF dose of 10 μg/kg/day. This dose and flux of TAF also resulted in adverse local inflammation and necrosis near the implant in rhesus macaques. The level of inflammation in the primates was markedly lower in the placebo group than in the active-implant group. The histological inflammatory response to the TAF implant at 4 and 12 weeks in primates was graded as a severe reaction. Thus, while we were able to achieve a sustained target dose, we observed an unacceptable inflammatory response locally at the implant tissue interface.

Agonistic muscles lose approximately 20% of their individual torque generating capacity when activated with their agonistic muscles compared to when stimulated in isolation. In this study, we (i) tested if this loss in torque was accompanied by a corresponding loss in force, thereby testing the potential role of changes in moment arms between conditions; (ii) removed all inter-muscular connections between the quadriceps muscles, thus determining the potential role of inter-muscular force transmission; and (iii) systematically changed the inter-muscular pressure by performing experiments at different activation/force levels, thereby exploring the possible role of inter-muscular pressure in the loss of torque capacity with simultaneous muscle activation. Experiments were performed in a New Zealand White rabbit quadriceps model (n=5). Torque and force were measured during activation of femoral nerve branches that supply the individual quadriceps muscles while activating these branches simultaneously and in isolation. Regardless of joint angle and inter-muscular connections between muscles, the differences in torque values between the simultaneous and the isolated activation of the quadriceps muscles were also observed for the directly measured force values. Mean differences in simultaneous and isolated muscle activation remained similar between the intact and separated conditions: torque difference (21±5% of maximum isometric torque of intact condition [MICtorque], versus 19±6% MICtorque respectively) and for force (18±3% MICforce versus 19±7% MICforce respectively). The absolute torque loss was independent of the force, and thus presumably the inter-muscular pressures. Based on these results, we conclude that neither moment arm, inter-muscular pressure nor inter-muscular force transmission seems to be the primary cause for the torque deficit observed during simultaneous compared to isolated muscle activation. The mechanisms underlying loss of force capacity during agonistic muscle contraction remain unknown.

INTRODUCTION AND HYPOTHESIS: New Zealand white rabbits are an inexpensive large-animal model. This study explored the rabbit as a model for mesh-augmented colpopexy using the intra-abdominal vagina. We hypothesized that polypropylene mesh would negatively impact rabbit vaginal smooth muscle (VSM) morphology and contractile function, similar to the nonhuman primate (NHP)—the established model for prolapse mesh evaluation. METHODS: Restorelle was implanted onto the vagina of ten rabbits via lumbar colpopexy after a hysterectomy. Ten rabbits served as sham. Twelve weeks post-implantation, the vagina was excised and VSM morphology and vaginal contractility were assessed. Outcome measures were compared using independent samples t and Mann-Whitney U tests with a Bonferroni correction, where appropriate. Results from the rabbits were compared with published NHP data. RESULTS: Animals had similar age, parity and BMI. VSM was 18% thinner after Restorelle implantation, P = 0.027. Vaginal contractility was 43% decreased in response to 120 mM KCl (P = 0.003), similar to the 46% reduction observed in the NHP vagina implanted with Restorelle (P = 0.027). Three meshes wrinkled in vivo, resulting in dramatic thinning of the underlying vagina in the area of the mesh causing a mesh exposure. CONCLUSIONS: Polypropylene mesh negatively impacts VSM morphology and vaginal contractility in the rabbit, similar to the NHP, suggesting that the rabbit may serve as an alternative large-animal model. The vaginal thinning and appearance of a mesh exposure in the area of a mesh wrinkle suggest the rabbit may also serve as a model for understanding the pathophysiology of mesh exposure.

Objective The aim of this study was to evaluate and compare the effect of three clinically applicable screw hole diameters on rabbit femoral torsional structural properties. Sample Eighteen pairs of skeletally mature New Zealand White rabbit femora (36 bones). Materials and Methods Femora with a bicortical hole at mid-diaphysis from one of the 3-drill bit sizes, 1.1 mm, 1.5 mm, 2.0 mm, and intact bones were studied. Each bone was bi-axially loaded in a servo-hydraulic load frame with the bone positioned so the neutral axis of torsion was aligned with the centre of the bone diaphysis. Axial compression to 35% body weight was applied to represent compression at stance, and rapid external torsion was applied to failure. Torque and angular deformation data were plotted for each test, with pre-yield and post-yield stiffnesses derived. Yield and failure torques and angles were determined, along with calculated yield, failure and post-yield energies. Results Failure torque was reduced compared with that of intact bone; weakened by 37% in 1.1-mm hole models, 53% in 1.5-mm hole models and 65% in 2.0-mm hole models. The torque angular deformation curves lacked plastic deformation. Conclusions and Clinical Relevance This study demonstrates the unique, brittle biomechanics of rabbit bone. Based on data from other species that strength loss of no more than 50% is acceptable when placing orthopaedic implants, no defect greater than 1.1 mm (15% bone diameter) is recommended in rabbit femora.

Pulmonary surfactant preparations extracted from natural sources have been used to treat millions of newborn babies with respiratory distress syndrome (RDS) and can possibly also be used to treat other lung diseases. Due to costly production and limited supply of animal-derived surfactants, synthetic alternatives are attractive. The water insolubility and aggregation-prone nature of the proteins present in animal-derived surfactant preparations have complicated development of artificial surfactant. A non-aggregating analog of lung surfactant protein C, SP-C33Leu is used in synthetic surfactant and we recently described an efficient method to produce rSP-C33Leu in bacteria. Here rSP-C33Leu obtained by salt precipitation of bacterial extracts was purified by two-step liquid gel chromatography and analyzed using mass spectrometry and RP-HPLC, showing that it is void of modifications and adducts. Premature New Zealand White rabbit fetuses instilled with 200mg/kg of 2% of rSP-C33Leu in phospholipids and ventilated with a positive end expiratory pressure showed increased tidal volumes and lung gas volumes compared to animals treated with phospholipids only. This shows that rSP-C33Leu can be purified from bacterial lipids and that rSP-C33Leu surfactant is active against experimental RDS.

The New Zealand White rabbit has been widely used as a model of limbal stem cell deficiency (LSCD). Current techniques for experimental induction of LSCD utilize caustic chemicals, or organic solvents applied in conjunction with a surgical limbectomy. While generally successful in depleting epithelial progenitors, the depth and severity of injury is difficult to control using chemical-based methods. Moreover, the anterior chamber can be easily perforated while surgically excising the corneal limbus. In the interest of creating a safer and more defined LSCD model, we have therefore evaluated a mechanical debridement technique based upon use of the AlgerBrush II rotating burr. An initial comparison of debridement techniques was conducted in situ using 24 eyes in freshly acquired New Zealand White rabbit cadavers. Techniques for comparison (4 eyes each) included: (1) non-wounded control, (2) surgical limbectomy followed by treatment with 100% (v/v) n-heptanol to remove the corneal epithelium (1-2 min), (3) treatment of both limbus and cornea with n-heptanol alone, (4) treatment of both limbus and cornea with 20% (v/v) ethanol (2-3 min), (5) a 2.5-mm rounded burr applied to both the limbus and cornea, and (6) a 1-mm pointed burr applied to the limbus, followed by the 2.5-mm rounded burr applied to the cornea. All corneas were excised and processed for histology immediately following debridement. A panel of four assessors subsequently scored the degree of epithelial debridement within the cornea and limbus using masked slides. The 2.5-mm burr most consistently removed the corneal and limbal epithelia. Islands of limbal epithelial cells were occasionally retained following surgical limbectomy/heptanol treatment, or use of the 1-mm burr. Limbal epithelial cells were consistently retained following treatment with either ethanol or n-heptanol alone, with ethanol being the least effective treatment overall. The 2.5-mm burr method was subsequently evaluated in the right eye of 3 live rabbits by weekly clinical assessments (photography and slit lamp examination) for up to 5 weeks, followed by histological analyses (hematoxylin & eosin stain, periodic acid-Schiff stain and immunohistochemistry for keratin 3 and 13). All 3 eyes that had been completely debrided using the 2.5-mm burr displayed symptoms of ocular surface failure as defined by retention of a prominent epithelial defect (∼40% of corneal surface at 5 weeks), corneal neovascularization (2-3 quadrants), reduced corneal transparency and conjunctivalization of the corneal surface (demonstrated by the presence of goblet cells and/or staining for keratin 13). In conclusion, our findings indicate that the AlgerBrush II rotating burr is an effective method for the establishment of ocular surface failure in New Zealand White rabbits. In particular, we recommend use of the 2.5-mm rotating burr for improved efficiency of epithelial debridement and safety compared to surgical limbectomy.

Aquaporins (AQPs) are important for ocular homeostasis and function. While AQP expression has been investigated in ocular tissues of human, mouse, rat and dog, comprehensive data in rabbits are missing. As rabbits are frequently used model organisms in ophthalmic research, the aim of this study was to analyze mRNA expression and to localize AQPs in the rabbit eye. The results were compared with the data published for other species. In cross sections of New Zealand White rabbit eyes AQP0 to AQP5 were labeled by immunohistology and analyzed by confocal microscopy. Immunohistological findings were compared to mRNA expression levels, which were analyzed by quantitative reverse transcription real time polymerase chain reaction (qRT-PCR). The primers used were homologous against conserved regions of AQPs. In the rabbit eye, AQP0 protein expression was restricted to the lens, while AQP1 was present in the cornea, the chamber angle, the iris, the ciliary body, the retina and, to a lower extent, in optic nerve vessels. AQP3 and AQP5 showed immunopositivity in the cornea. AQP3 was also present in the conjunctiva, which could not be confirmed for AQP5. However, at a low level AQP5 was also traceable in the lens. AQP4 protein was detected in the ciliary non-pigmented epithelium (NPE), the retina, optic nerve astrocytes and extraocular muscle fibers. For most tissues the qRT-PCR data confirmed the immunohistology results and vice versa. Although species differences exist, the AQP protein expression pattern in the rabbit eye shows that, especially in the anterior section, the AQP distribution is very similar to human, mouse, rat and dog. Depending on the ocular regions investigated in rabbit, different protein and mRNA expression results were obtained. This might be caused by complex gene regulatory mechanisms, post-translational protein modifications or technical limitations. However, in conclusion the data suggest that the rabbit is a useful in-vivo model to study AQP function and the effects of direct and indirect intervention strategies to investigate e. g. mechanisms for intraocular pressure modulation or cornea transparency regulation.