RESUMO
Peripheral nerve injuries are common, and full functional recovery after injury is achieved in only 10% of patients. The sympathetic nervous system plays many critical roles in maintaining bodily homeostasis, but it has rarely been studied in the context of peripheral nerve injury. The extent of postganglionic sympathetic neuronal functions in distal targets in the periphery is currently unclear. To better explore the role of sympathetic innervation of peripheral targets, a surgical "knock-out" model provides an alternative approach. Although this can be achieved chemically, chemical destruction of postganglionic sympathetic neurons can be nonspecific and dose-dependent. The use of a surgical lumbar sympathectomy in mice, once thought to be "virtually not practicable" in small animals, allows for specific targeting of postganglionic sympathetic neurons that innervate the hind limbs. This manuscript describes how to surgically remove the L2-L5 lumbar sympathetic ganglia from a mouse as a survival surgery, which reliably decreases the hind paw sweat response and the number of sympathetic axons in the sciatic nerve.
Assuntos
Simpatectomia , Animais , Camundongos , Simpatectomia/métodos , Gânglios Simpáticos/cirurgia , Região Lombossacral/inervação , Região Lombossacral/cirurgia , Nervo Isquiático/cirurgia , Nervo Isquiático/lesões , Membro Posterior/inervação , Membro Posterior/cirurgiaRESUMO
BACKGROUND: Lymphaticovenous anastomosis is widely used in lymphedema management. Although its effectiveness in reducing edema in patients can be clinically observed, evaluating the long-term outcomes of this technique can be complex. This study established an animal model to assess the outcomes of lymphaticovenous anastomosis technique at 15 and 30-days post-surgery using indocyanine green lymphography, Patent Blue V dye injection, and histopathological examination. METHODS: An experimental model was established in the hindlimbs of 10 rabbits using the popliteal vein and afferent lymphatic vessels in the popliteal area. The subjects were divided into two groups: the first group (n = 5) underwent patency assessment at 0 and 15 days, and the second group (n = 5) at 0 and 30-days, resulting in 20 anastomoses. Patency was verified at 0, 15, and 30-days using indocyanine green lymphography and Patent Blue V injection. Histopathological examinations were performed on the collected anastomosis samples. RESULTS: The patency rate was 90% (19/20) initially, 60% (6/10) at 15 days post-surgery, and 80% (8/10) at 30-days. The average diameter of lymphatic vessels and veins was 1.0 mm and 0.8 mm, respectively. The median number of collateral veins was 3; the median surgical time was 65.8 min. Histopathology revealed minimal endothelial damage and inflammatory responses due to the surgical sutures, with vascular inflammation and thrombosis in a single case. Local vascular neoformations were observed. CONCLUSION: This study highlights the reliability and reproducibility of using rabbits as experimental models for training in lymphaticovenous anastomosis technique owing to the accessibility of the surgical site and dimensions of their popliteal vasculature.
Assuntos
Anastomose Cirúrgica , Verde de Indocianina , Vasos Linfáticos , Linfedema , Linfografia , Microcirurgia , Animais , Coelhos , Anastomose Cirúrgica/métodos , Vasos Linfáticos/cirurgia , Vasos Linfáticos/diagnóstico por imagem , Microcirurgia/métodos , Linfografia/métodos , Linfedema/cirurgia , Grau de Desobstrução Vascular , Modelos Animais , Modelos Animais de Doenças , Veia Poplítea/cirurgia , Membro Posterior/irrigação sanguínea , Membro Posterior/cirurgia , Corantes , Corantes de RosanilinaRESUMO
OBJECTIVE: To assess the feasibility of a novel transcoronal approach for the treatment of axial type 3 cysts of the palmar/plantar aspect of the distal phalanx (P3). STUDY DESIGN: Ex vivo, experimental study. SAMPLE POPULATION: Ten cadaveric specimens, four forelimbs and six hindlimbs. METHODS: All cadaveric specimens underwent radiographically guided drilling, followed by cortical screw placement. The cartilage was macroscopically assessed after disarticulation of the distal interphalangeal joint. The entry point and trajectory were evaluated with computed tomography. Results were categorized as: axial, near-axial and abaxial. The minimal distance from the outer margin of the drill hole and the proximal border of the subchondral bone plate was measured using frontal computed tomographic slices. RESULTS: Eight of the 10 screws were in an axial to near-axial position and nine followed the desired axial to near-axial trajectory. One screw was inserted axially but continued in an abaxial trajectory. Iatrogenic damage to the joint cartilage, flexor cortex and solar canal of P3 was not observed. All cortical screws were placed close to the proximal subchondral bone-plate of P3. CONCLUSION: The desired axial/near-axial drilling and screw placement, under radiographic guidance, was achieved in nine out of 10 specimens. CLINICAL SIGNIFICANCE: This novel technique seems promising for the treatment of inaccessible P3 cysts. Additional studies are required to investigate its feasibility in clinical cases, and the long-term outcome following transcystic screw placement of type 3 P3 cysts.
Assuntos
Cadáver , Animais , Parafusos Ósseos/veterinária , Membro Anterior/cirurgia , Cistos Ósseos/veterinária , Cistos Ósseos/cirurgia , Cistos Ósseos/diagnóstico por imagem , Membro Posterior/cirurgia , CavalosRESUMO
Femoral fractures are often considered lethal for adult horses because femur osteosynthesis is still a surgical challenge. For equine femur osteosynthesis, primary stability is essential, but the detailed physiological forces occurring in the hindlimb are largely unknown. The objective of this study was to create a numerical testing environment to evaluate equine femur osteosynthesis based on physiological conditions. The study was designed as a finite element analysis (FEA) of the femur using a musculoskeletal model of the loading situation in stance. Relevant forces were determined in the musculoskeletal model via optimization. The treatment of four different fracture types with an intramedullary nail was investigated in FEA with loading conditions derived from the model. The analyzed diaphyseal fracture types were a transverse (TR) fracture, two oblique fractures in different orientations (OB-ML: medial-lateral and OB-AP: anterior-posterior) and a "gap" fracture (GAP) without contact between the fragments. For the native femur, the most relevant areas of increased stress were located distally to the femoral head and proximally to the caudal side of the condyles. For all fracture types, the highest stresses in the implant material were present in the fracture-adjacent screws. Maximum compressive (-348 MPa) and tensile stress (197 MPa) were found for the GAP fracture, but material strength was not exceeded. The mathematical model was able to predict a load distribution in the femur of the standing horse and was used to assess the performance of internal fixation devices via FEA. The analyzed intramedullary nail and screws showed sufficient stability for all fracture types.
Assuntos
Fraturas do Fêmur , Fixação Interna de Fraturas , Membro Posterior , Animais , Cavalos/fisiologia , Fenômenos Biomecânicos , Fraturas do Fêmur/veterinária , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/veterinária , Fixação Interna de Fraturas/métodos , Membro Posterior/cirurgia , Análise de Elementos Finitos , Fêmur/cirurgia , Modelos Biológicos , Suporte de Carga , Fixação Intramedular de Fraturas/veterinária , Fixação Intramedular de Fraturas/instrumentaçãoRESUMO
OBJECTIVE: The aim of this study was to perform gait analysis using a pressure-sensitive walkway in dogs submitted to high (total) or low amputation (partial) of one forelimb or hindlimb. STUDY DESIGN: A total of 39 dogs met the inclusion criteria. The reasons for the amputations were motor vehicle accidents in 38 dogs and possible limb malformation in 1 dog. The amputee dogs were divided into four groups: G1 (n = 10)-high forelimb; G2 (n = 10)-low forelimb; G3 (n = 9)-high hindlimb; and G4 (n = 10)-low hindlimb. For kinetic evaluation, the dogs were walked across a pressure-sensitive walkway. RESULTS: In dogs with forelimb amputation, the percentage of body weight (%BW) distribution on the contralateral forelimb was 50.7% in cases of high amputation and 55.5% in cases of low amputation, while the %BW distribution on the hindlimbs, mainly in the ipsilateral hindlimb, was 27.9% in cases of high amputation and 27.1% in cases of low amputation. In cases of high amputation of the hindlimb, the %BW distribution was 71.5% on the forelimbs and 29.7% on the contralateral hindlimb, while in cases of low amputation, the distribution was mainly for the contralateral hindlimb and ipsilateral forelimb. No statistical difference was noted between the amputation levels, except for the contralateral limb in cases of low and high amputation of the hindlimbs concerning the overload percentage and %BW distribution. CONCLUSION: The amputation level of one forelimb did not influence the %BW distribution; however, in the hindlimb, this was higher for the contralateral limb in dogs submitted to high amputation.
Assuntos
Amputação Cirúrgica , Membro Anterior , Análise da Marcha , Membro Posterior , Animais , Cães/cirurgia , Membro Posterior/cirurgia , Análise da Marcha/veterinária , Masculino , Amputação Cirúrgica/veterinária , Feminino , Marcha , Pressão , Doenças do Cão/cirurgia , AmputadosRESUMO
BACKGROUND: Adipose stem cells (ASCs) are a promising cell-based immunotherapy because of their minimally invasive harvest, high yield, and immunomodulatory capacity. In this study, the authors investigated the effects of local versus systemic ASC delivery on vascularized composite allotransplant survival and alloimmune regulation. METHODS: Lewis rats received hind-limb transplants from Brown Norway rats and were administered donor-derived ASCs (passage 3 or 4, 1 × 10 6 cells/rat) locally in the allograft, or contralateral limb, or systemically at postoperative day 1. Recipients were treated intraperitoneally with rabbit anti-rat lymphocyte serum on postoperative days 1 and 4 and daily tacrolimus for 21 days. Limb allografts were monitored for clinical signs of rejection. Donor cell chimerism, immune cell differentiation, and cytokine expression in recipient lymphoid organs were measured by flow cytometric analysis. The immunomodulation function of ASCs was tested by mixed lymphocyte reaction assay and ASC stimulation studies. RESULTS: Local-ASC-treated recipients achieved significant prolonged allograft survival (85.7% survived >130 days; n = 6) compared with systemic-ASC and contralateral-ASC groups. Secondary donor skin allografts transplanted to the local-ASC long-term surviving recipients accepted permanently without additional immunosuppression. The increases in donor cell chimerism and regulatory T-cells were evident in blood and draining lymph nodes of the local-ASC group. Moreover, mixed lymphocyte reaction showed that ASCs inhibited donor-specific T-cell proliferation independent of direct ASC-T-cell contact. ASCs up-regulated antiinflammatory molecules in response to cytokine stimulation in vitro. CONCLUSION: Local delivery of ASCs promoted long-term survival and modulated alloimmune responses in a full major histocompatibility complex-mismatched vascularized composite allotransplantation model and was more effective than systemic administration. CLINICAL RELEVANCE STATEMENT: ASCs are a readily available and abundant source of therapeutic cells that could decrease the amount of systemic immunosuppression required to maintain limb and face allografts.
Assuntos
Alotransplante de Tecidos Compostos Vascularizados , Ratos , Animais , Coelhos , Ratos Endogâmicos Lew , Ratos Endogâmicos BN , Membro Posterior/cirurgia , Aloenxertos , Citocinas , Células-Tronco , Sobrevivência de Enxerto , ImunossupressoresRESUMO
BACKGROUND: Lymphedema constitutes a major unsolved problem in plastic surgery. To identify novel lymphedema treatments, preclinical studies are vital. The surgical mouse lymphedema model is popular and cost-effective; nonetheless, a synthesis and overview of the literature with evidence-based guidelines is needed. The aim of this review was to perform a systematic review to establish best practice and support future high-quality animal studies exploring lymphedema treatments. METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching four databases (PubMed, Embase, Web of Science, and Scopus) from inception-September 2022. The Animals in Research Reporting In Vivo Experiments 2.0 (ARRIVE 2.0) guidelines were used to evaluate reporting quality. Studies claiming to surgically induce lymphedema in the hindlimb of mice were included. RESULTS: Thirty-seven studies were included. Four main models were used. (1) Irradiation+surgery. (2) A variation of the surgery used by (1) + irradiation. (3) Surgery only (SPDF-model). (4) Surgery only (PLND-model). Remaining studies used other techniques. The most common measurement modality was the caliper. Mean quality coefficient was 0.57. Eighteen studies (49%) successfully induced sustained lymphedema. Combination of methods seemed to yield the best results, with an overrepresentation of irradiation, the removal of two lymph nodes, and the disruption of both the deep and superficial lymph vessels in the 18 studies. CONCLUSION: Surgical mouse hindlimb lymphedema models are challenged by two related problems: (1) retaining lymphedema for an extended period, that is, establishing a (chronic) lymphedema model (2) distinguishing lymphedema from post-operative edema. Most studies failed to induce lymphedema and used error-prone measurements. We provide an overview of studies claiming to induce lymphedema and advocate improved research via five evidence-based recommendations to use: (1) a proven lymphedema model; (2) sufficient follow-up time, (3) validated measurement methods; (4) ARRIVE-guidelines; (5) contralateral hindlimb as control.
Assuntos
Vasos Linfáticos , Linfedema , Camundongos , Animais , Linfedema/etiologia , Linfedema/cirurgia , Linfedema/patologia , Linfonodos/cirurgia , Vasos Linfáticos/patologia , Membro Posterior/cirurgia , Extremidade Inferior , Modelos Animais de DoençasRESUMO
BACKGROUND: The management of feline hindlimb full-thickness skin defects is challenging. On the other hand, the use of a semitendinosus (ST) myocutaneous flap for their coverage has not been reported. OBJECTIVES: To describe the ST flap and compare it with second intention healing for managing hindlimb full-thickness skin defects. METHODS: In 12 purpose-bred laboratory domestic short-haired cats, two wounds were made on each tibia. The wounds in group A (n = 12) were covered with ST flaps, and those in group B (n = 12) were left to heal by second intention. In both groups, clinical assessment scoring and planimetry were performed between one-30 d postoperatively. Computed tomography-angiography (CTA) was performed on days zero, 10, and 30, and histological examinations were performed on days zero and 14 and at 6 and 12 mon postoperatively. RESULTS: Statistically significant differences in the clinical assessment scores were observed between groups A and B on days 14 (p = 0.046) and 21 (p = 0.016). On the other hand, the time for complete healing was similar in the two groups. CTA revealed significant differences in the muscle width (day 0 compared to days 10 and 30 [p = 0.001, p = 0.026, respectively], and days 10 to 30 [p = 0.022]), ST muscle density, and the caliber of the distal caudal femoral artery and vein (day 0 compared to day 10 [p < 0.001], and days 10 to 30 [p < 0.001]). Histologically significant differences in inflammation, degeneration, edema, neovascularization, and fibrosis were observed on day 14 compared to zero and 6 mon, but no differences were found between the time interval of 6 and 12 mon. CONCLUSIONS: An ST flap can be used effectively to manage hindlimb full-thickness skin defects.
Assuntos
Músculos Isquiossurais , Retalho Miocutâneo , Procedimentos de Cirurgia Plástica , Gatos/cirurgia , Animais , Procedimentos de Cirurgia Plástica/veterinária , Transplante de Pele/veterinária , Membro Posterior/cirurgia , Resultado do TratamentoRESUMO
Lymphedema is a common condition often associated with cancer and its treatment, which leads to damage to the lymphatic system, and current treatments are mostly palliative rather than curative. Its high incidence among oncologic patients indicates the need to study both normal lymphatic function and pathologic dysfunction. To reproduce chronic lymphedema, it is necessary to choose a suitable experimental animal. Attempts to establish animal models are limited by the regenerative capacity of the lymphatic system. Among the potential candidates, the rabbit hindlimb is easy to handle and extrapolate to the human clinical scenario, making it advantageous. In addition, the size of this species allows for better selection of lymphatic vessels for vascularized lymph node resection. In this study, we present a procedure of vascular lymph node resection in the rabbit hindlimb for inducing secondary lymphedema. Anesthetized animals were subjected to circumferential measurement, patent blue V infiltration, and indocyanine green lymphography (ICG-L) using real-time near-infrared fluorescence, a technique that allows the identification of single popliteal nodes and lymphatic channels. Access to the identified structures is achieved by excising the popliteal node and ligating the medial and lateral afferent lymphatics. Special care must be taken to ensure that any lymphatic vessel that joins the femoral lymphatic system within the thigh without entering the popliteal node can be identified and ligated. Postoperative evaluation was performed at 3, 6, and 12 months after induction using circumferential measurements of the hindlimb and ICG-L. As demonstrated during follow-up, the animals developed dermal backflow that was maintained until the 12th month, making this experimental animal useful for novel long-term evaluations in the management of lymphedema. In conclusion, the approach described here is feasible and reproducible. Additionally, during the time window presented, it can be representative of human lymphedema, thus providing a useful research tool.
Assuntos
Vasos Linfáticos , Linfedema , Animais , Humanos , Coelhos , Linfedema/diagnóstico por imagem , Linfedema/etiologia , Linfedema/cirurgia , Linfografia/efeitos adversos , Linfografia/métodos , Excisão de Linfonodo , Linfonodos/patologia , Vasos Linfáticos/diagnóstico por imagem , Vasos Linfáticos/cirurgia , Vasos Linfáticos/patologia , Membro Posterior/cirurgia , Membro Posterior/patologia , Verde de IndocianinaRESUMO
Patients with severe traumatic injuries and tissue loss require complex surgical reconstruction. Vascularized composite allotransplantation (VCA) is an evolving reconstructive avenue for transferring multiple tissues as a composite subunit. Despite the promising nature of VCA, the long-term immunosuppressive requirements are a significant limitation due to the increased risk of malignancies, end-organ toxicity, and opportunistic infections. Tissue engineering of acellular composite scaffolds is a potential alternative in reducing the need for immunosuppression. Herein, the procurement of a rat hindlimb and its subsequent decellularization using sodium dodecyl sulfate (SDS) is described. The procurement strategy presented is based upon the common femoral artery. A machine perfusion-based bioreactor system was constructed and used for ex vivo decellularization of the hindlimb. Successful perfusion decellularization was performed, resulting in a white translucent-like appearance of the hindlimb. An intact, perfusable, vascular network throughout the hindlimb was observed. Histological analyses showed the removal of nuclear contents and the preservation of tissue architecture across all tissue compartments.
Assuntos
Alotransplante de Tecidos Compostos Vascularizados , Animais , Reatores Biológicos , Circulação Extracorpórea , Membro Posterior/cirurgia , Humanos , Perfusão , RatosRESUMO
This prospective clinical trial evaluated the effects of epidural anesthesia (EA) placed at the lumbosacral compared to the L5-L6 junction in dogs undergoing hindlimb orthopedic surgery. In all, 98 dogs were randomly assigned to receive injection at either L7-S1 (LS group) or L5-L6 (LL group) at the same local anesthetic regimen (1 mg/kg bupivacaine 0.5% and 0.1 mg/kg morphine 1%). Fentanyl (1 µg/kg) was the intraoperative rescue analgesia (iRA) administered if mean arterial pressure increased by 30% above pre-stimulation value. Procedural failure, iRA, hypotension, motor block resolution, and postoperative side effects were recorded. There were 7/47 (15%) epidural procedural failures in the LS group and 8/51 (16%) (P=1.00) in the LL group; iRA was administered in 21/40 (52%) LS group dogs and in 13/43 (30%) LL group dogs, respectively (P=0.047). The incidence of hypotension was 10/40 (25%) and 16/43 (37%) in the LS group and the LL group, respectively (P=0.25). Proprioceptive residual deficit at 8 hr after EA was recorded in 3/26 (12%) in group LS dogs and in 13/26 (50%) group LL dogs, respectively (P=0.01). The proprioceptive residual deficit at 24 hr in one dog (LL group) resolved within 36 hr. No episodes of postoperative urinary retention, pruritus or neurological damage were recorded. The L5-L6 EA decreased significantly iRA but delays the proprioceptive recovery time. Further studies are needed to determine whether a lower bupivacaine dose reduces the duration of the residual block retaining the same incidence of iRA.
Assuntos
Anestesia Epidural , Doenças do Cão , Procedimentos Ortopédicos , Analgésicos Opioides , Anestesia Epidural/efeitos adversos , Anestesia Epidural/veterinária , Anestésicos Locais/farmacologia , Animais , Bupivacaína/farmacologia , Doenças do Cão/cirurgia , Cães , Membro Posterior/cirurgia , Morfina/farmacologia , Morfina/uso terapêutico , Procedimentos Ortopédicos/veterinária , Dor Pós-Operatória/veterináriaRESUMO
A 10-year-old spayed female Golden Retriever was referred for hindlimb lameness. A firm mass was palpated over the right caudal pelvis. Computed tomography revealed an osteolytic bone region and an associated periosteal reaction in the ischium, including the acetabulum. The histological diagnosis was sarcoma of unknown origin. A mid-to-caudal partial hemipelvectomy was performed to remove the mass. Femoral head and neck osteotomy was performed to allow hindlimb preservation. Following surgery, the dog regained satisfactory hindlimb use over time and was alive for 821 days with no recurrence or metastatic disease. This report indicates that mid-to-caudal partial hemipelvectomy with femoral head and neck osteotomy is technically feasible and allows for tumor control with preservation of the hindlimb and its function.
Assuntos
Neoplasias Ósseas , Doenças do Cão , Hemipelvectomia , Animais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Feminino , Hemipelvectomia/veterinária , Membro Posterior/cirurgia , ÍsquioRESUMO
PURPOSE: Mohs' paste, which is composed of zinc chloride and zinc oxide starch, is used for hemostasis of superficial malignancy in the clinical setting. We investigated the concentration of intramuscular zinc in mice after Mohs' paste application and evaluated its relationship with angiogenesis from the perspective of blood flow levels within 24 h. METHODS: Male C57BL/6JJmsSlc mice were administered single dose of Mohs' paste at 25%, 50%, and 75% after unilateral hind limb surgery, and glycerin, a viscosity modifier, was administered to the control group (0%). Hind limb blood flow levels were measured with a laser Doppler perfusion imaging system (n = 6). The amounts of intramuscular zinc and vascular endothelial growth factor-A (VEGF-A) expression were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and western blotting, respectively (n = 5 or 3). RESULTS: Blood flow levels were significantly decreased in the 50% group after 8 h, and significantly decreased in the 25% and 50% groups after 24 h. Intramuscular zinc was significantly increased in the 50% and 75% groups after 8 h. Western blotting showed that VEGF-A levels were significantly increased in the 25% and 50% groups after 8 h. Based on analytical experiments and biological investigation, we predicated the pharmacological effect of Mohs' paste and found over 50% of it is critical in the blood flow and angiogenesis suppression after more than 8 h of its application. CONCLUSIONS: The results suggest that the mechanism of blood flow suppression is independent of VEGF-A levels and might suppress future angiogenesis. Our findings support that of previous studies, in which Mohs' paste was expected to induce hemostasis and suppress angiogenesis. It is an excellent ointment that facilitates hemostasis by suppressing blood flow regardless of angiogenesis, and may be apt for situations where hemostasis is required in the clinical setting.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Circulação Sanguínea/efeitos dos fármacos , Cloretos/administração & dosagem , Membro Posterior/cirurgia , Músculo Esquelético/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Compostos de Zinco/administração & dosagem , Zinco/análise , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Cloretos/química , Cloretos/farmacologia , Relação Dose-Resposta a Droga , Glicerol/química , Membro Posterior/diagnóstico por imagem , Fluxometria por Laser-Doppler , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/diagnóstico por imagem , Imagem de Perfusão , Espectrofotometria Atômica , Compostos de Zinco/química , Compostos de Zinco/farmacologiaRESUMO
Background: Skeletal muscle ischemia/reperfusion (I/R) injury is an important clinical issue that can cause remote organ injury. Although its pathogenesis has not been fully elucidated, recent studies have suggested that damage-associated molecular patterns (DAMPs) are mediators of remote organ injury in sterile inflammation. The purpose of this study was to investigate the possible involvement of DAMPs, including the nuclear proteins high-mobility group box 1 (HMGB1) and histone H3, in the pathogenesis of skeletal muscle I/R injury in mice. Methods: Hindlimb ischemia was induced in mice through bilateral ligation of inguinal regions using rubber grommets. Reperfusion was induced by cutting the rubber grommets after 2-12 h of ischemic period. Survival rates, localization of HMGB1 and histone H3 in the gastrocnemius muscle, and circulating HMGB1 and histone H3 levels were analyzed. The effect of anti-HMGB1 and anti-histone H3 antibodies on survival was analyzed in mice with I/R injury. Results: All mice with hindlimb ischemia survived for at least 36 h, while all mice died within 24 h if the hindlimbs were reperfused after ischemia for 4-12 h. Immunohistochemical analysis revealed that HMGB1 translocated from the nucleus to the cytoplasm in the ischemic gastrocnemius muscle, while histone H3 was confined to the nucleus. Accordingly, serum HMGB1 levels were significantly elevated in mice with hindlimb I/R compared with normal mice or mice with hindlimb ischemia (P < 0.05). Serum histone H3 levels were not elevated after I/R. Treatment with anti-HMGB1 antibodies significantly improved survival of mice with hindlimb I/R injury compared with control antibodies (P < 0.05). Conclusions: HMGB1, but not histone H3, translocated to the cytoplasm during skeletal muscle ischemia, and was released into the systemic circulation after reperfusion in mice with I/R injury. Treatment with anti-HMGB1 antibodies partially improved survival.
Assuntos
Alarminas/metabolismo , Proteína HMGB1/metabolismo , Membro Posterior/patologia , Histonas/metabolismo , Músculo Esquelético/fisiologia , Traumatismo por Reperfusão/metabolismo , Alarminas/imunologia , Animais , Anticorpos Bloqueadores/administração & dosagem , Modelos Animais de Doenças , Proteína HMGB1/imunologia , Membro Posterior/cirurgia , Histonas/imunologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transporte Proteico , Traumatismo por Reperfusão/imunologiaRESUMO
Complete extremity regeneration in mammals is restricted to distal amputations of the digit tip, the terminal phalanx (P3). In mice, P3 regeneration is mediated via the formation of a blastema, a transient population of progenitor cells that form from the blending of periosteal and endosteal/marrow compartmentalized cells that undergo differentiation to restore the amputated structures. Compartmentalized blastema cells are formed independently, and periosteal compartment-derived cells are required for restoration of amputated skeletal length. P3 regenerative capacity is progressively attenuated at increasingly more proximal amputation levels, eventually resulting in regenerative failure. The continuum of regenerative capacity within the P3 wound milieu is a unique model to investigate mammalian blastema formation in response to distal amputation, as well as the healing response associated with regenerative failure at proximal amputation levels. We report that P3 proximal amputation healing, previously reported to result in regenerative failure, is not an example of complete regenerative failure, but instead is characterized by a limited bone regeneration response restricted to the endosteal/marrow compartment. The regeneration response is mediated by blastema formation within the endosteal/marrow compartment, and blastemal osteogenesis progresses through intramembranous ossification in a polarized proximal to distal sequence. Unlike bone regeneration following distal P3 amputation, osteogenesis within the periosteal compartment is not observed in response to proximal P3 amputation. We provide evidence that proximal P3 amputation initiates the formation of fibrotic tissue that isolates the endosteal/marrow compartment from the periosteal compartment and wound epidermis. While the fibrotic response is transient and later resolved, these studies demonstrate that blastema formation and fibrosis can occur in close proximity, with the regenerative response dominating the final outcome. Moreover, the results suggest that the attenuated proximal P3 regeneration response is associated with the absence of periosteal-compartment participation in blastema formation and bone regeneration.
Assuntos
Amputação Cirúrgica , Regeneração Óssea/fisiologia , Membro Posterior/fisiologia , Osteogênese/fisiologia , Cicatrização/fisiologia , Ferimentos e Lesões/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Membro Posterior/diagnóstico por imagem , Membro Posterior/cirurgia , Camundongos , Ferimentos e Lesões/patologia , Microtomografia por Raio-XRESUMO
OBJECTIVE: To report the outcome of horses used in western performance disciplines after deep branch lateral plantar neurectomy/fasciotomy surgery for hind limb proximal suspensory desmopathy (PSD). STUDY DESIGN: Retrospective analysis. SAMPLE POPULATION: Twenty-one client-owned horses. METHODS: Medical records were reviewed (2009-2019) for horses involved in western performance disciplines that had been treated with deep branch lateral plantar neurectomy and plantar fasciotomy for lameness due to hind limb PSD. Follow-up was obtained by reexamination and/or verbal interviews with owners >2 years postoperatively. RESULTS: Sixteen quarter horses and five paints were used for western pleasure (14/21), barrel racing (2/21), cutting (1/21), steer wrestling (1/21), working cow horse (1/21), team roping (1/21) and reining (1/21). A median duration of 8 months was required before horses were able to resume training or athletic work. Nine horses were able to return to a similar or higher level of athletic use, nine horses returned to a lower level of athletic performance, and three horses could not return to intended function. Owner satisfaction with outcome after the procedure was high (16/21), average (3/21), and low (2/21). CONCLUSION: Deep branch lateral plantar neurectomy and plantar fasciotomy allowed most horses to resume some athletic function as western performance horses. CLINICAL SIGNIFICANCE: These results provide evidence of potential outcomes when considering surgical treatment of hind limb PSD in western performance horses.
Assuntos
Denervação/veterinária , Fasciíte Plantar/veterinária , Membro Posterior/patologia , Doenças dos Cavalos/cirurgia , Ligamentos/patologia , Nervo Tibial/cirurgia , Animais , Denervação/estatística & dados numéricos , Fasciíte Plantar/cirurgia , Feminino , Membro Posterior/cirurgia , Cavalos , Ligamentos/cirurgia , Masculino , Estudos Retrospectivos , Nervo Tibial/patologia , Resultado do TratamentoRESUMO
Previous prostheses for replacing a missing limb following amputation must be worn externally on the body. This limits the extent to which prostheses could physically interface with biological tissues, such as muscles, to enhance functional recovery. The objectives of our study were to (1) test the feasibility of implanting a limb prosthesis, or endoprosthesis, entirely within living skin at the distal end of a residual limb, and (2) identify effective surgical and post-surgical care approaches for implanting endoprostheses in a rabbit model of hindlimb amputation. We iteratively designed, fabricated, and implanted unjointed endoprosthesis prototypes in six New Zealand White rabbits following amputation. In the first three rabbits, the skin failed to heal due to ishemia and dehiscence along the sutured incision. The skin of the final three subsequent rabbits successfully healed over the endoprotheses. Factors that contributed to successful outcomes included modifying the surgical incision to preserve vasculature; increasing the radii size on the endoprostheses to reduce skin stress; collecting radiographs pre-surgery to match the bone pin size to the medullary canal size; and ensuring post-operative bandage integrity. These results will support future work to test jointed endoprostheses that can be attached to muscles.
Assuntos
Membros Artificiais , Procedimentos de Cirurgia Plástica , Implantação de Prótese , Amputação Cirúrgica , Animais , Estudos de Viabilidade , Membro Posterior/diagnóstico por imagem , Membro Posterior/cirurgia , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/cirurgia , Desenho de Prótese , Coelhos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Suporte de CargaRESUMO
Background: Loco-regional anesthetic techniques are considered important in the multimodal approach to analgesia in both human and veterinary medicine. No such techniques are described in the alpaca, bar the use of epidural. This is in part due to the lack of anatomical description for this species. While this limitation exists, the use of ultrasound guidance makes peripheral nerve blocks a viable possibility in the alpaca. Case description: A 12-month-old alpaca was referred for the treatment of a septic left tarso-crural joint. Due to a poor prognosis, amputation of the limb under general anesthesia was performed. Sciatic and psoas compartment blocks were attempted with the ultrasound-guided injection of ropivacaine prior to the start of the procedure. While the femoral nerve was possible to visualize, no obturator nerve was identified. A 5-year old alpaca was also referred for a left hind lateral claw removal, due to a squamous cell carcinoma. The sciatic nerve block was performed prior to the claw amputation under general anesthesia. No changes in heart and respiratory rate, or blood pressure suggestive of nociception, were observed in either of these cases. At the end of both the procedures, the patients experienced uneventful recoveries characterized by the ability to maintain the standing position, interest in food, and normal behavior. Conclusion: This report identifies the ease of performance and the challenges encountered using the ultrasound-guided psoas compartment and sciatic nerve blocks in the alpaca. It is our hope that this report encourages the use of ultrasound-guided loco-regional techniques in this species.
Assuntos
Anestésicos Locais/administração & dosagem , Camelídeos Americanos/cirurgia , Manejo da Dor/veterinária , Ropivacaina/administração & dosagem , Amputação Cirúrgica/veterinária , Analgesia/veterinária , Anestesia por Condução/veterinária , Anestesia Geral/veterinária , Animais , Feminino , Nervo Femoral/diagnóstico por imagem , Membro Posterior/cirurgia , Bloqueio Nervoso/veterinária , Nervo Obturador/diagnóstico por imagem , Nervos Periféricos/diagnóstico por imagem , Nervo Isquiático/diagnóstico por imagem , Ultrassonografia/veterináriaRESUMO
BACKGROUND: Tourniquets are widely used during extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimum inhibitory concentration (t > MIC) in porcine subcutaneous adipose tissue and calcaneal cancellous bone during 3 clinically relevant tourniquet application scenarios. METHODS: Twenty-four female Danish Landrace pigs were included. Microdialysis catheters were placed bilaterally for sampling of cefuroxime concentrations in calcaneal cancellous bone and subcutaneous adipose tissue, and a tourniquet was applied to a randomly picked leg of each pig. Subsequently, the pigs were randomized into 3 groups to receive 1.5 g of cefuroxime by intravenous injection 15 minutes prior to tourniquet inflation (Group A), 45 minutes prior to tourniquet inflation (Group B), and at the time of tourniquet release (Group C). The tourniquet duration was 90 minutes in all groups. Dialysates and venous blood samples were collected for 8 hours after cefuroxime administration. Cefuroxime and various ischemic marker concentrations were quantified. RESULTS: Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 µg/mL) in calcaneal cancellous bone and subcutaneous adipose tissue throughout the 90-minute tourniquet duration in Groups A and B. Cefuroxime administration at the time of tourniquet release (Group C) resulted in concentrations of >4 µg/mL for approximately of 3.5 hours in the tissues on the tourniquet side. Furthermore, tourniquet application induced ischemia (increased lactate:pyruvate ratio) and cell damage (increased glycerol) in subcutaneous adipose tissue and calcaneal cancellous bone. Tissue ischemia was sustained for 2.5 hours after tourniquet release in calcaneal cancellous bone. CONCLUSIONS: Administration of cefuroxime (1.5 g) in the 15 to 45-minute window prior to tourniquet inflation resulted in sufficient concentrations in calcaneal cancellous bone and subcutaneous adipose tissue throughout the 90-minute tourniquet application. Furthermore, tourniquet-induced tissue ischemia fully resolved 2.5 hours after tourniquet release. CLINICAL RELEVANCE: Cefuroxime administration 15 to 45 minutes prior to tourniquet inflation seems to be a safe window. If the goal is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at the time of tourniquet release.
Assuntos
Antibacterianos , Antibioticoprofilaxia , Cefuroxima , Microdiálise , Torniquetes , Animais , Feminino , Tecido Adiposo/química , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Osso Esponjoso/química , Cefuroxima/administração & dosagem , Cefuroxima/uso terapêutico , Membro Posterior/cirurgia , Injeções Intravenosas , Testes de Sensibilidade Microbiana , Microdiálise/métodos , Suínos , Fatores de TempoRESUMO
OBJECTIVE: To describe clinical applications of computer-assisted orthopedic surgery (CAOS) in horses with a navigation system coupled with a cone beam computed tomography unit. STUDY DESIGN: Retrospective clinical case series. ANIMALS: Thirteen adult horses surgically treated with CAOS. METHODS: Medical records were searched for horses that underwent CAOS between 2016 and 2019. Data retrieved included signalment, diagnosis, lameness grade prior to surgery, surgical technique and complications, anesthesia and surgery time, and information pertaining to the perioperative case management and outcome. RESULTS: In 10 cases, surgical implants were placed in the proximal phalanx, third metatarsal bone, ulna, or medial femoral condyle. In one case, navigated transarticular drilling was performed to promote ankylosis of the distal tarsal joints. In another case, an articular fragment of the middle phalanx was removed with the help of CAOS guidance. In the final case, a focal osteolytic lesion of the calcaneal tuber was curetted with the aid of CAOS. In seven cases, a purpose-built frame was used for the surgical procedure. All surgeries were performed successfully and according to the preoperative plan. CONCLUSION: Computer-assisted orthopedic surgery can be an integral part of the clinical case management in equine surgery. To optimize workflow and time-efficiency, the authors recommend designating one team for operative planning and another for the execution of the surgical plan. Specialized equipment, such as the purpose-built frame, will further improve CAOS applications in equine surgery. CLINICAL SIGNIFICANCE: After they have become familiar with the operational principles, equine surgeons can readily apply CAOS for a broad spectrum of indications.