Rectovaginal fistula model in the New Zealand white rabbit

Introduction and hypothesis  

The purpose of this study was to create an animal model to study rectovaginal fistula repair.     

Effects of noise exposure and hypercholesterolemia on auditory function in the New Zealand white rabbit

An association between hypercholesterolemia and high-frequency hearing loss has been suggested previously. Most data have been epidemiologic, and only recently have experimental studies appeared supporting this observed association. It is unclear whether this hearing loss is related solely to hypercholesterolemia or if it is a consequence of cholesterol-induced vascular changes. The New Zealand White rabbit was used to study the auditory effects of noise, hypercholesterolemia, and the combination of both. Auditory function was evaluated with far-field monitoring of click-evoked auditory brain stem responses by comparing latency/intensity functions and absolute click-evoked thresholds. Hypercholesterolemia was maintained for only 3 weeks, theoretically eliminating atherosclerotic vascular changes as a mechanism contributing to observed changes. Auditory function was unchanged after 3 weeks of hypercholesterolemia. Also, the changes observed after noise exposure were comparable between the normal and the hypercholesterolemic groups. We conclude that if hypercholesterolemia contributes to high-frequency hearing loss, the pathophysiology is related to cholesterol-induced vascular changes, not solely to hypercholesterolemia.     

MAC of sevoflurane in humans and the New Zealand white rabbit

The minimum alveolar concentration of sevoflurane necessary to prevent movement in 50 per cent of patients (MAC) was determined to be 2.05 per cent in 20 adult surgical patients. Because this value was higher than the only other experimentally determined human MAC value for sevoflurane (1.71 per cent), MAC was also determined in New Zealand white rabbits. Comparisons of the MAC ratios of sevoflurane to other volatile anaesthetics in both the human and the rabbit suggest that the human MAC value we obtained for sevoflurane is consistent with experimental determinations of MAC of other volatile anaesthetics in humans.     

Interposition grafts for rectovaginal fistula repair in the New Zealand white rabbit

Introduction and hypothesis

The objective was to use an animal model to study different types of interposition grafts for rectovaginal fistula repair.

Methods

Twelve New Zealand white rabbits underwent surgical creation of a rectovaginal fistula, followed by repair. Four repair techniques were studied; three with interposition grafts and one control group without a graft. Animals were euthanized at 4-week intervals and underwent gross and histologic analysis.

Results

The mean rectovaginal wall thickness was greatest in the control group (5.6 mm) and thinnest in the autologous rectus fascia (4.2 mm) and porcine small intestine submucosa (5.1 mm) groups. The polypropylene graft had a mean thickness of 5.4 mm and elicited a strong, protracted inflammatory response. All fistulas were successfully closed except one porcine small intestine submucosa repair.

Conclusions

There is no benefit from interposition graft use for rectovaginal fistula repair in our New Zealand white rabbit model.     

Auto‐crosslinked hyaluronic acid gel accelerates healing of rabbit flexor tendons in vivo

This study's purpose was to assess the in vivo effect of auto‐crosslinked hyaluronic acid (HA) gel, a natural HA derivative with increased viscosity and tissue residence time, on adhesions and healing of injured and surgically repaired rabbit digital flexor tendons. The second and third right deep digital flexor tendons from 48 rabbits (n = 96 tendons) were cut and repaired with a modified Kessler and running peripheral suture. Animals were randomized to two groups, receiving either HA gel or saline injected around both freshly repaired tendons. After 2, 3, 6, and 12 weeks, six rabbits in each group were euthanized. Tendon pull‐out force and breaking strength were measured as a value for adhesion formation and tendon healing, respectively. A histological assessment of adhesions and healing was related to the mechanical results. A significantly faster increase in breaking strength was found in HA gel‐treated compared to saline‐treated tendons; this coincided with a significantly accelerated tissue repair response after injury. No significant difference in adhesion formation was found between the two groups at any time. Our results indicate a significant acceleration of in vivo healing of tendons treated with HA gel. Adhesion formation was unaffected. These results could have important clinical value in promoting rehabilitation after tendon injury. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:408–415, 2009     

Flexibility analysis of posterolateral fusions in a New Zealand white rabbit model.

STUDY DESIGN: Biomechanics of posterolateral spinal fusion were studied in an in vivo rabbit model. OBJECTIVES: To determine the extent of stabilization produced by posterolateral lumbar fusion and to test the hypothesis that motions are not completely eliminated after successful fusion. SUMMARY OF BACKGROUND DATA: Previous human cadaveric studies, clinical studies, and animal studies have attempted to characterize the biomechanics of posterolateral fusion. Such studies have been limited by either methods of fusion modeling or methods of stability testing. No previous study has examined biologic fusion with a physiologic biomechanical testing technique. METHODS: Ten adult New Zealand white rabbits underwent L5-L6 intertransverse process fusion using autogenous iliac crest bone graft. Rabbits were killed 5 weeks after surgery. Only one time point was studied. This time point was chosen because previous pull-apart studies have shown plateauing of rabbit fusion mass strength and stiffness around this time. Spines were then harvested and evaluated with manual palpation and an established flexibility testing protocol. Resulting data were compared with previously acquired, nonoperative spine flexibility data. RESULTS: Two animals were excluded because of complications. Of those that were fused (n = 5), biomechanical testing revealed significant decreases in flexion (81%), extension (61%), and right and left lateral bending (67% and 83%, respectively) (P < 0.01). CONCLUSIONS: These findings define the amount of motion reduction that can be expected with posterolateral fusions in the rabbit model at 5 weeks. These results suggest that motion was significantly decreased but was not eliminated.     

Effects of glans penis augmentation using hyaluronic acid gel for premature ejaculation

The main limitation of medical treatment for premature ejaculation is recurrence after withdrawal of medication. We evaluated the effect of glans penis augmentation using injectable hyaluronic acid (HA) gel for the treatment of premature ejaculation via blocking accessibility of tactile stimuli to nerve receptors. In 139 patients of premature ejaculation, dorsal neurectomy (Group I, n=25), dorsal neurectomy with glandular augmentation (Group II, n=49) and glandular augmentation (Group III, n=65) were carried out, respectively. Two branches of dorsal nerve preserving that of midline were cut at 2 cm proximal to coronal sulcus. For glandular augmentation, 2 cc of HA was injected into the glans penis, subcutaneously. At 6 months after each procedure, changes of glandular circumference were measured by tapeline in Groups II and III. In each groups, ejaculation time, patient's satisfaction and partner's satisfaction were also assessed. There was no significant difference in preoperative ejaculation time among three groups. Preoperative ejaculation times were 89.2+/-40.29, 101.54+/-59.42 and 96.5+/-52.32 s in Groups I, II and III, respectively. Postoperative ejaculation times were significantly increased to 235.6+/-58.6, 324.24+/-107.58 and 281.9+/-93.2 s in Groups I, II and III, respectively (P<0.01). The percentage of postoperative satisfaction in both patient and his partner was 68% (17/25) and 44% (7/16) in Group I, 80% (39/49) and 66% (25/38) in Group II and 75% (49/65) and 62% (32/52) in Group III, respectively. Maximal glandular girth was significantly increased from 9.16+/-0.59 to 10.95+/-0.4 cm in Group II and 8.95+/-0.54 to 11.67+/-0.71 cm in Group III, respectively. These results suggest that glandular augmentation with injectable HA gel is a safe and effective modality to reduce sensory of glans penis. Long-term follow-up for residual volume and efficacy should be requested to establish its precise therapeutic potentials in premature ejaculation.     

Biomechanical evaluation of the New Zealand white rabbit lumbar spine: a physiologic characterization

Physiologic motions of the human, sheep, and calf lumbar spines have been well characterized. The size, cost, and ease of care all make the rabbit an attractive alternative choice for an animal lumbar spine model. However, comparisons of normal biomechanical characteristics of the rabbit lumbar spine have not been made to the spines of larger species. The purpose of this study was to establish baseline physiologic kinematic data for the rabbit lumbar spine. Ten skeletally mature New Zealand white rabbit osteoligamentous spines were obtained. L4-L7 spine segments were harvested and mounted. Multi-directional flexibility testing was performed by applying pure moments up to 0.27 Nm. Resulting rotations were measured using an Optotrak system. Data were analyzed for each intervertebral level in the three planes of rotation. The three levels tested had roughly similar range of motion (ROM). The mean (SD) angular ROMs in flexion for L4-L5, L5-L6, L6-L7 were 12.10° (2.59°), 12.38° (2.70°), and 15.17° (3.22°), respectively. The ROMs in extension were 5.86° (1.21°), 5.58° (1.48°), and 6.13° (2.03°). Lateral bending and axial rotation were roughly symmetric due to the symmetric nature of the spine. For right lateral bending, the ROMs were 8.25° (2.44°), 4.96° (1.70°), and 4.25° (1.20°). For left axial rotation, the ROMs were 1.23° (1.16°), 0.35° (0.61°), 0.87° (0.64°). Neutral zone (NZ) was on average 60% (29%) of ROM for the motions studied. The physiologic ROM of the New Zealand white rabbit lumbar spine was found to be similar between the rabbit and human. This relatively conserved physiologic flexibility supports the use of the rabbit as a model of the lumbar spine for kinematic studies. However, the overall NZ was found to be a greater percentage of ROM in the rabbit than the corresponding percentage in the human (60% as compared to 25%). This suggested that the rabbit lumbar spine has a greater laxity than that of the human. Received: 23 August 1999 Revised: 15 December 1999 Accepted: 26 January 2000     

The effect of hyaluronic acid on cartilage in the immobilized rabbit knee

Out of 30 adult rabbits, 20 had one knee immobilized with a plaster of Paris cast for 6 or 12 weeks, and 10 rabbits were used as untreated controls. Prior to immobilization, 10 knees were injected with high-molecular weight hyaluronic acid. The articular cartilage of the femoral condyles was studied by light microscopy, whereas that of the patella and tibia was analyzed biochemically. Degenerative changes of the articular cartilage similar to those seen in arthrosis were observed after 6 weeks. The intraarticular injection of hyaluronic acid did not prevent these changes; instead, the reparative processes seemed inhibited.     

The effect of hyaluronic acid on cartilage in the immobilized rabbit knee

Out of 30 adult rabbits, 20 had one knee immobilized with a plaster of Paris cast for 6 or 12 weeks, and 10 rabbits were used as untreated controls. Prior to immobilization, 10 knees were injected with high-molecular weight hyaluronic acid. The articular cartilage of the femoral condyles was studied by light microscopy, whereas that of the patella and tibia was analyzed biochemically. Degenerative changes of the articular cartilage similar to those seen in arthrosis were observed after 6 weeks. The intraarticular injection of hyaluronic acid did not prevent these changes; instead, the reparative processes seemed inhibited.     

A new antibacterial carrier of hyaluronic acid gel

Background Postoperative infection following total joint arthroplasty is thought to be one of the most serious and devastating complications. To develop an effective treatment for this complication, we tested a bioabsorbable antibacterial carrier that is made from novel cross-linked hyaluronic acid (HA) gel and gentamicin (GM). Methods Antibacterial activity of the carrier was evaluated by the agar diffusion test, direct contact test, in vivo mouse model, and in vivo rabbit osteomyelitis model. Results GM-containing HA gel suppressed bacterial growth both in vitro and in vivo. In the rabbit osteomyelitis model, beads coated with HA gel containing GM did not disturb bone ongrowth in the femoral stem. Conclusions Our bioabsorbable carrier of antibiotic-containing HA gel is effective for prophylactic treatment or treatment of an actual deep infection following total joint arthroplasty.     

Tibial epiphyseal development: a cross-sectional histologic and histomorphometric study in the New Zealand white rabbit

Sequential histomorphometric studies on the developing rabbit tibia from birth to skeletal maturity demonstrate that growth plate height lessens as longitudinal growth diminishes. Differing rates of development proximally and distally are documented. Distally, growth plate height, width, and area and total epiphyseal area peak or reach near maximum values by 3 weeks, whereas proximally, they do so by 8 weeks (except for height, which also peaks at 3 weeks). The distal growth plate is being obliterated by 16 weeks, at which time the proximal growth plate remains well structured and open. The distal tibia and fibula develop as one tissue mass. The articular cartilage and epiphyseal cartilage are continuous from birth, whereas a single ossification center and a single growth plate are present by 8 weeks. The data point to the presence of intrinsic growth plate, as well as systemic, control mechanisms affecting skeletal growth. Knowledge of temporal and quantitative features of epiphyseal and growth plate development will greatly aid in the elucidation of the underlying controls.     

Evaluation of a knitted polytetrafluoroethylene mesh placed intraperitoneally in a New Zealand white rabbit model

Background

The intraperitoneal application of surgical mesh remains a controversial issue because of possible complications, especially adhesion and fistula formation. This study aimed to assess the potential of a knitted polytetrafluoroethylene (PTFE) mesh for intraabdominal implantation.

Methods

Twenty-eight 5?×?5?cm samples of knitted macroporous PTFE mesh and light-weight polypropylene mesh (LW-PP) were implanted intraperitoneally in 14 New Zealand white rabbits in a randomized manner and fixed using eight polypropylene stitches. After 90?days, the adhesion formation, adhesion score, shrinkage, strength of fixation to the abdominal wall, and histologic biocompatibility were assessed.

Results

No intraoperative or anesthesia-related complications or mesh infection were recorded. The average area covered by adhesions was 4.7?±?7.2% for the PTFE and 36.4?±?36.1% for the LW-PP. The median adhesion score was 0 for the PTFE and 8 for the LW-PP. Shrinkage was 36.9?±?12.9% for the PTFE mesh and 12.6?±?8.72% for the LW-PP. The mesh-to-abdominal wall fixation strength was almost the same for both materials (PTFE 3.6?±?1.9 vs. LW-PP 3.6?±?2.9). The inflammatory cell count was almost the same for the two groups, with no statistically significant difference. The width of the inner granuloma was equal (PTFE 10.5?±?0.9 vs. LW-PP 11.1?±?0.9). The outer granuloma was reduced significantly in the PTFE group (PTFE 23.0?±?2.1 vs. LW-PP 33.6?±?7.9). One of the animals in the PTFE group died on postoperative day 12 because of ileus. The reason was an adhesion of the small intestine to the polypropylene fixation stitch, which caused small intestine strangulation.

Conclusions

The knitted PTFE mesh induces fewer intraperitoneal adhesions of lower density than the light-weight polypropylene mesh. The strength of the knitted PTFE mesh fixation to the abdominal wall is comparable with that of the light-weight polypropylene mesh, but the shrinkage is greater. The biocompatibility of the knitted PTFE mesh is comparable with that of the light-weight polypropylene implant.     

rhBMP-6 stimulated osteoprogenitor cells enhance posterolateral spinal fusion in the New Zealand white rabbit.

BACKGROUND CONTEXT: The nonunion rate after posterolateral spinal fusion can be as high as 35%. This has stimulated interest in the development of techniques for enhancing new bone formation, including the addition of bioactive peptides or the use of cell-based therapies, including genetically modified cells. In previous studies we have demonstrated that exposing autologous, marrow-derived osteoprogenitor cells to a recombinant human bone morphogenetic protein-6 (rhBMP-6) containing extracellular matrix induces osteoblastic differentiation, and that these cells are capable of increasing new bone formation. Growth of autologous cells on a synthetic rhBMP-6 containing matrix yields a population of stimulated osteoprogenitor cells, without the expense of adding large amounts of rhBMP-6 directly, or the risks inherent in the use of genetically altered cells. PURPOSE: This study was performed to evaluate the potential of rhBMP-6 stimulated osteoprogenitor cells (stOPC) to enhance the rate and strength of posterolateral spinal fusion. STUDY DESIGN: Prospective in vivo animal study OUTCOME MEASURES: Radiographic evidence of spinal fusion, biomechanical testing of explanted spines, histological analysis of new bone formation METHODS: Single-level posterolateral spinal arthrodeses were performed in 69 New Zealand white rabbits. Autologous marrow stem cells were concentrated and then plated on an rhBMP-6-rich extracellular matrix synthesized by genetically engineered mouse C3H10T1/2 cells. Animals in Groups I (n=18) and II (n=18) received autografts of 30M and 60M rhBMP-6 stOPCs in guanidine extracted demineralized bone matrix (gDBM), respectively, whereas those in Group III (n=13) received iliac crest bone graft (ICBG). Those in Group IV (n=10) received gDBM, and those in Group V (n=10) underwent decortication only. Assessment of fusion was made with serial radiographs, manual palpation of the explanted spines, and biomechanical testing. The fusion masses from two animals each in Groups I, II, and IV were evaluated histologically. RESULTS: Fifty-three animals were available for analysis at the conclusion of the study. In these animals, the arthrodesis rate was significantly higher after treatment with rhBMP-6 stOPCs (77% for both Groups I and II by palpation) than ICBG, gDBM, or decortication alone (Group III=55%, IV=20% and V=0%, respectively). Similarly, the peak loads to failure of the fusion masses in Groups I and II (212.5+/-37.8 N and 234.6+/-45.7 N) were significantly greater than the corresponding values in the other groups (Group III=155.9+/-36.4N, Group IV=132.7+/-59.9N, and Group V=92.8+/-18.4N), though when only the fused specimens in Groups I, II, and III were compared, only Group II was significantly different than Group III (234.6+/-45.7N and 155.9+/-36.4N, respectively). The fusion masses in the rhBMP-6 stOPC-treated animals were typified by a thin, fusiform cortical shell, newly formed trabecular bone emanating from the decorticated transverse processes, and residual unremodeled gDBM carrier particles. The fusion masses in the gDBM treated bones were morphologically similar, though they contained less newly formed bone. CONCLUSIONS: The use of rhBMP-6 stOPCs in a carrier of gDBM significantly enhanced the rate and strength of single-level posterolateral spinal arthrodeses in the New Zealand white rabbit, compared with ICBG, gDBM, and decortication alone. Our results confirm that the stimulation of marrow-derived osteoprogenitor cells by growing them on a rhBMP-6 containing extracellular matrix is feasible. Further investigation is warranted to determine the relative contribution of rhBMP-6 stimulation and the number of cells implanted, as well as strategies for optimizing the technique for clinical application.     

A comparison of the direct cerebral vasodilating potencies of halothane and isoflurane in the New Zealand white rabbit

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 X 100 g-1 X min-1; second group received a background anesthetic of high-dose pentobarbital, which resulted in an initial CMRO2 of 1.76 +/- 0.16 ml X 100 g-1 X min-1. In rabbits receiving a background of morphine sulfate/N2O, halothane resulted in a significantly greater CBF (65 +/- 10 ml X 100 g-1 X min-1) than did isoflurane (40 +/- 5 ml X 100 g-1 X 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.(ABSTRACT TRUNCATED AT 250 WORDS)     

Augmentation of glans penis using injectable hyaluronic acid gel

Recently, injectable hyaluronic acid gel has been widely used in soft-tissue augmentation. We performed this study to identify the feasibility of hyaluronic acid gel for the augmentation of the glans penis. In experiment I, 0.2 cm(3) of hyaluronic acid gel (HA) was injected into the dermis of the glans penis of 25 New Zealand white rabbits via a 30 G needle. At 3, 7, 14, 30, and 90 days after injection, histological changes of glans were studied, respectively. In experiment II, 0.5 cm(3) of HA was injected into the dermis of the glans penis of 14 Beagle dogs via a 27 G needle. At 6 months after injection, histological changes of the glans penis were also evaluated. At the time of autopsy, the lung, liver, and spleen were studied for systemic adverse reaction in each separate experiment.In experiment I, various sized cavities filled with amorphous basophilic materials were noted in the lamina propria and corpus spongiosum of the glans penis. All implants were positively stained on alcian blue. The intensity decreased in a time-dependent manner. Until 14 days, minimal inflammatory reactions were noted, but no signs of inflammation were identified at 90 days. With the gradual decrease of inflammation, fibrosis and deposition of collagen were noted. In experiment II, implants were well maintained at 6 months after injection in the lamina propria. Grade 1 of the inflammatory reaction was noted in one case. In both the experiments, all the specimens were free from any foreign body reaction and systemic adverse reactions.In conclusion, these results suggest that hyaluronic acid gel can be easily injected into the lamina propria of the glans penis and reside until 6 months. Injectable hyaluronic acid gel has a potential as a new bioimplant for the augmentation of the glans penis.     

新西兰大白兔髓核组织在自身椎管内巨噬细胞浸润的动态变化及其意义

[目的] 制作游离型腰椎间盘突出动物模型,观察并探讨游离髓核组织重吸收的可能机制,为临床保守治疗某些类型腰椎间盘突出症提供新的思路和依据.[方法] 健康雄性新西兰大白兔90只,随机分为三组:模型组60只,假模型组24只,对照组6只.模型组前方入路制作游离型腰椎间盘突出动物模型,假模型组取相同手术入路,但仅暴露至纤维环而不做后续处理,对照组不做任何处理.模型组及假模型组分别于术后2、4、6、8、10、12周分批处死动物,取手术区间椎间盘标本.用免疫组化方法观察髓核组织中CD<,68><'+>巨噬细胞浸润情况.[结果]模型组移植的髓核组织不同程度缩小甚至消失,所有移植标本内均见CD<,68><'+>巨噬细胞浸润随时间延长而逐渐减少,假模型组仅纤维环外缘见少量CD<,68><'+>巨噬细胞浸润,其髓核及对照组髓核均未见CD<,68><'+>巨噬细胞浸润.[结论] (1)运用前方手术入路可建立游离型腰椎间盘突出动物模型;(2)游离髓核组织在硬膜外腔可逐渐被机体重吸收;(3)CD<,68><'+>巨噬细胞浸润在游离髓核组织重吸收过程中起到重要作用.