Murine Aseptic Surgical Model of Femoral Atrophic Nonunion.

Although bone repair is typically an efficient process, an inadequate healing response can occur, with approximately 5-20% of fractures developing nonunion. Even with improved healing strategies and external fixation devices, overall rate of nonunion has not been significantly reduced, particularly for atrophic nonunion. Atrophic nonunion is characterized by sparse or no callus formation and is difficult to treat clinically, resulting in long-term pain and functional limitation. Reliable preclinical models are needed to study the pathophysiology of atrophic nonunion to create better treatment options. The MouseNail kit (RISystem, Landquart, Switzerland) provides a highly standardized approach in which stabilized segmental bone defects are achieved through interlocked intramedullary nailing. However, reliably performing this surgery is technically challenging, particularly while maintaining strict asepsis. Skilled and aseptic surgical execution is important and necessary because it ensures optimal animal welfare and reproducibility. Therefore, the aim of this paper is to describe:•Novel modifications to the MouseNail kit that allow for: 1) a completely aseptic surgical environment, including description of a hanging limb orthopedic aseptic preparation and 2) a reduction in fracture gap size necessary for induction of atrophic nonunion.•Pre- to post-operative recommendations to facilitate successful performance of murine orthopedic survival surgery.

Mulberry Heart Disease and Hepatosis Dietetica in Farm Pigs (Sus scrofa domesticus) in a Research Setting.

Perioperative complications and deaths occurred while developing a novel surgical model of pediatric kyphosis in 10 to 12 kg male farm-raised Yorkshire piglets. All piglets appeared clinically normal preoperatively. Intraoperative complications included tachycardia, respiratory acidosis, and death. Postoperatively, clinical signs included posterior paresis, head pressing, prolonged anesthetic recovery, difficulty rising, and sudden death. Necropsies were performed on all piglets. Some morbidity and mortality were accurately attributed to the spinal surgery. However, the index piglet for this report died suddenly approximately 16 to 18 h after surgery. Necropsy of this animal revealed clear, serosanguineous pleural and pericardial effusions along with myocardial hemorrhage and hepatic lesions, consistent with mulberry heart disease and hepatosis dietetica, respectively. Serum vitamin E and selenium levels from this animal were below age-specific lab reference ranges. Clinical signs of vitamin E and selenium deficiency are most common in fast-growing weaner piglets. The added stress of major surgery may exacerbate the condition in young piglets. Resolution of morbidity and mortality in both juvenile and adult pigs occurred upon the use of an alternate vendor able to provide feed analyses meeting industry standards, although serum levels of vitamin E and selenium in similar ages and breed of swine were still occasionally slightly below reference ranges.

Efficacy of preanesthetic intramuscular administration of ephedrine for prevention of anesthesia-induced hypotension in cats and dogs.

To determine if the preanesthetic administration of ephedrine would prevent anesthesia-induced hypotension in dogs and cats, 10 cats were anesthetized with acepromazine, butorphanol, ketamine, and isoflurane, and 8 dogs were anesthetized with acepromazine, morphine, propofol, and halothane. Cats received ephedrine or saline 10 minutes after premedication. Dogs received ephedrine or saline at the time of premedication. Systolic arterial blood pressure, respiratory rate, heart rate, end-tidal CO2, O2 saturation, cardiac rhythm, and rectal temperature were recorded.The systolic arterial pressure in cats receiving saline was significantly lower than baseline at 10 minutes after premedication, and systolic arterial pressure was < 80 mmHg for the duration of anesthesia. In cats receiving ephedrine, the systolic arterial pressure was significantly lower than baseline for the duration of anesthesia, but systolic arterial pressure was not < 80 mmHg until 25 min after induction. In dogs, systolic arterial pressure was significantly lower than baseline by 5 and 40 min after pre-medication in dogs receiving saline and ephedrine, respectively. There was no difference in heart rate, respiratory rate, end-tidal CO2, rectal temperature, O2 saturation, or cardiac rhythm among treatment groups. Prophylactic ephedrine delayed, but did not prevent, the onset of hypotension.

Teaching Surgical Model Development in Research by Using Situated Learning and Instructional Scaffolding.

Resources detailing the scope, details, and duration for teaching and learning surgical model development in research are poorly described. Situated learning and instructional scaffolding are useful skill-building tools. Herein, we discuss educational theory in the context of a training paradigm for surgical researchers, using our experience with a nonunion femoral fracture model as an example. Stages of learning include cognitive, associative, and autonomous stages. In surgical training, the cognitive stage involves the acquisition of basic knowledge, including anatomy, surgical approach, instrumentation, and suturing, which can be taught by using books, videos, skeletons, and cadavers. To these basic skills, the associative stage adds advanced techniques-including anesthesia, asepsis, hemostasis, and the full surgical procedure-through mentored nonsurvival surgical experiences. After a mentor has assured competence, trainees perform supervised and then independent survival surgeries to complete the autonomous stage. Through these stages, instructional scaffolding is applied in the context of a situated learning environment in which trainees learn in a layered approach through their own experiences. Thus, the proposed training paradigm is structured to teach trainees how to think and act as surgeons so they can adapt and grow, rather than only to ensure technical competency in a specific model. Development and mastery of complex surgical models may require as long as 6 mo to achieve optimal outcomes, depending on the preexisting skill of the research surgeons, technical difficulty, and the stage of model evolution.

Creation of a Porcine Kyphotic Model.

STUDY DESIGN: Large animal study. OBJECTIVE: Create a thoracic hyperkyphotic deformity in an immature porcine spine, so that future researchers may use this model to validate spinal instrumentation and other therapies used in the treatment of hyperkyphosis. SUMMARY OF BACKGROUND DATA: Although several scoliotic animal models have been developed, there have been no reports of a thoracic hyperkyphotic animal model creation in an immature animal. The present study was designed to produce a porcine hyperkyphotic model by the time the pig weighed 25 kg, which corresponds to the approximate weight of a child undergoing surgery for early-onset scoliosis (EOS). METHODS: Successful surgical procedures were performed in 6 consecutive 10-kg (male, 5-week-old) immature Yorkshire pigs. Procedure protocol consisted of 1) a left thoracotomy at T10-T11, 2) screw placement at T9 and T11, 3) partial vertebrectomy at T10, 4) posterior interspinous ligament transection, and 5) placement of wire loop around screws and tightening. Weekly x-ray imaging was performed preoperatively and postoperatively, documenting progressively increasing kyphosis as the pig grew. Necropsy was performed 5-6 weeks after surgery, with CT, slab section, and histologic analysis. RESULTS: Average T9-T11 kyphosis (measured by sagittal Cobb angle) was 6.1° ± 1.4° (mean ± SD) preoperatively, 30.5° ± 1.0° immediately postoperation, and significantly increased to 50.3° ± 7.2° (p < .0001) over 5-6 weeks in 6 consecutive pigs at time of necropsy. CONCLUSIONS: An animal model of relatively more rigid-appearing thoracic hyperkyphotic deformities in immature pigs has been created. Subsequent studies addressing management of early-onset kyphosis with spinal instrumentation are now possible. LEVEL OF EVIDENCE: Level V.

Antiviral efficacy of nine nucleoside reverse transcriptase inhibitors against feline immunodeficiency virus in feline peripheral blood mononuclear cells.

OBJECTIVE: To compare cytotoxic effects and antiviral efficacy of 9 nucleoside reverse transcriptase inhibitors (NRTIs) against FIV in feline peripheral blood mononuclear cells. SAMPLE: Peripheral blood mononuclear cells obtained from 3 specific pathogen-free cats. PROCEDURES: 3 of the 9 NRTIs had not been previously assessed in feline cell lines. Cytotoxic effects were determined by colorimetric quantification of a formazan product resulting from bioreduction of a tetrazolium reagent by viable peripheral blood mononuclear cells; uninfected cells from 1 cat were used in these assays. Cells from all 3 cats were infected with a pathogenic clone of FIV, and in vitro antiviral efficacy of each NRTI was assessed with an FIV p24 antigen capture ELISA. RESULTS: Cytotoxic effects in feline peripheral blood mononuclear cells were observed only at concentrations > 10 µM for all 9 NRTIs. Comparison of the cytotoxic effect at the highest concentration investigated (500 µM) revealed that didanosine and amdoxovir were significantly less toxic than abacavir. All drugs induced a dose-dependent reduction of FIV replication. At the highest concentration investigated (10 µM), there was no significant difference in antiviral efficacy among the test compounds. CONCLUSIONS AND CLINICAL RELEVANCE: The evaluated NRTIs had low cytotoxicity against feline peripheral blood mononuclear cells and appeared to be safe options for further in vivo evaluation for the treatment of FIV-infected cats. There was no evidence suggesting that the newly evaluated compounds would be superior to the existing NRTIs for reducing FIV burden of infected cats.