Bupivacaine and liposomal bupivacaine do not produce prolonged perineural anesthesia in a lameness model and are detectable beyond clinical effect in conditioned Thoroughbreds.

OBJECTIVE: To determine (1) the dose of liposomal bupivacaine (LB) to eliminate grade 2 of 5 lameness, the (2) duration of analgesia of LB versus bupivacaine hydrochloride (BH), and (3) LB pharmacokinetics versus BH. METHODS: A reversible lameness model was validated in conditioned Thoroughbred horses (n = 12), aged 3 to 10 years. A dose-response trial compared subjective and objective lameness following abaxial sesamoid block with 25 mg BH/nerve or 30, 60, or 133 mg LB/nerve (n = 3/group). The LB dose that eliminated lameness and reduced lameness for the longest was used for blinded, randomized, crossover pharmacokinetic/pharmacodynamic trials (n = 12/group). Data were analyzed using a paired t test or Wilcoxon signed-rank test, P < .05. RESULTS: The 133-mg/nerve dose of LB eliminated lameness in 3 of 3 horses in the dose-response trial, and lameness returned at 6, 36, and 72 hours. In the pharmacokinetic/pharmacodynamic trials, time to return of lameness greater than or equal to starting lameness was longer for LB compared to BH on subjective (LB, 12 hours, 4 to 24 hours; BH, 4 hours, 4 to 12 hours) and objective (LB, 12 hours, 4 to 24 hours; BH, 4 hours, 2 to 6 hours) evaluations. The terminal half-life was not different between formulations (LB, 17.8 hours ± 10.1; BH, 12.4 hours ± 6.3); however, LB had increased area under the concentration-versus-time curve from time 0 to infinity (LB, 388 ng·h/mL ± 117; BH, 63 ng·h/mL ± 18) and mean residence time (LB, 17.6 hours ± 2.4; BH, 3.9 hours ± 1.6). CONCLUSIONS: Liposomal bupivacaine analgesia duration was greater than BH, but the median time until lameness returned was only 12 hours. Bupivacaine is quantifiable in serum and urine beyond loss of clinical effect. CLINICAL RELEVANCE: A single, high-dose injection of LB is not effective for providing perineural analgesia over several days. Bupivacaine is detectable after the effect of the drug has worn off.

Antimicrobial prophylaxis is not indicated for horses undergoing general anaesthesia for elective orthopaedic MRI.

BACKGROUND: Post-anaesthetic fever is a known complication of general anaesthesia, however, its incidence in horses undergoing elective magnetic resonance imaging (MRI) is unknown. OBJECTIVE: To determine the incidence of post-anaesthetic fever in horses undergoing elective orthopaedic MRI and determine whether prophylactic antimicrobial therapy would be associated with a reduction in the incidence of post-anaesthetic fever. We hypothesised that prophylactic antimicrobials would be associated with a reduction in the incidence of post-anaesthetic fever. STUDY DESIGN: Retrospective cross-sectional study. METHODS: This retrospective study included 791 elective orthopaedic MRIs in systemically healthy horses between June 2006 and March 2020 that recovered from general anaesthesia and did not undergo surgery or intensive medical therapy soon after recovery. Potential factors associated with post-anaesthetic fever were evaluated using multivariable logistic regression. Case signalment, travel time, preanaesthetic haematology and fibrinogen abnormalities, use of prophylactic antimicrobials, peri-anaesthetic nonsteroidal anti-inflammatories, anaesthesia time and recovery time were all evaluated for association with post-anaesthetic fever. RESULTS: Of 791 MRI cases, 44 (5.6%) developed a post-anaesthetic fever. Horses that received prophylactic antimicrobials were [odds ratio (OR) 3.8, 95% confidence interval (CI) 1.98-7.46; p ≤ 0.001] more likely to develop a post-anaesthetic fever than those that did not receive antimicrobials. Young horses (1-4 years of age) were (OR 2.8, 95% CI 1.26-6.17; p = 0.01) more likely to develop fever compared with adult horses (≥5 years of age). MAIN LIMITATIONS: Limitations of this study pertain to retrospective analysis including nonrandomised case selection and incomplete data records. CONCLUSIONS: While fever may indicate infection, the majority of early post-anaesthetic fevers resolved before discharge from the hospital with no identified cause. The use of prophylactic antimicrobials to reduce the risk of post-anaesthetic fever for elective MRI is not supported by this study.

CONTEXTO: Febre é uma complicação comum após anestesia geral. Contudo, a incidência de febre em cavalos submetidos à ressonância magnética (RM) é desconhecida. OBJETIVO: Determinar a incidência de febre pós­anestésica em cavalos submetidos à RM devido à lesões ortopédicas e determinar se terapia antimicrobiana é necessária para reduzir a incidência de febre pós­anestésica. Nossa hipótese é que o uso de antimicrobianos é associado com a redução da incidência de febre pós­anestésica. DELINEAMENTO DO ESTUDO: Estudo retrospectivo transversal. METODOLOGIA: Esse estudo retrospectivo incluiu 791 equinos submetidos à RM por motivos ortopédicos, entre Junho de 2006 e Março de 2020, que recuperaram de anestesia geral, e não foram submetidos à cirurgia ou terapia intensa logo após a recuperação. Fatores que potencialmente poderiam ser associados com febre pós­anestésica foram avaliados utilizando regressão logística multivariada. Informações do paciente, como sexo e idade, tempo de viagem, anormalidades nos exames de sangue (hemograma e bioquímico) pré­anestésico, uso profilático de antimicrobianos, uso de anti­inflamatório não­esteroidal no período peri­anestésico, tempo de anestesia, e tempo de recuperação foram avaliados para possível associação com febre pós­anestésica. RESULTADOS: Dos 791 casos de RM, 44 (5.6%) desenvolveram febre pós­anestésica. Cavalos que receberam terapia antimicrobiana profilática foram (OR 3.8, 95% CI 1.98­7.46; p ≤ 0.001) vezes mais prováveis de desenvolverem febre pós­anestésica do que aqueles que não receberam antimicrobianos. Cavalos jovens (1­4 anos de idade) foram OR 2.8, 95% CI 1.26­6.17; p = 0.01) vezes mais prováveis de desenvolverem febre comparado com cavalos adultos (≥5 anos de idade). PRINCIPAIS LIMITAÇÕES: As limitações deste estudo são aquelas de uma análise retrospectiva, incluindo a seleção não randomizada dos pacientes e prontuários incompletos. CONCLUSÕES: Enquanto febre pode indicar a presença de infecção, a maioria das febres no período logo após anestesia se resolveram antes da alta do hospital e não tiveram nenhuma causa identificada. O uso profilático de antimicrobianos para reduzir a possível chance de febre pós­anestésica em casos de RM eletiva não é suportada por este estudo.

Kinematics of the equine distal sesamoid (navicular) bone of the thoracic limb.

OBJECTIVE: To quantify the translation and angular rotation of the distal sesamoid bone (DSB) using computed tomography (CT) and medical modeling software. SAMPLE: 30 thoracic limbs from equine cadavers. PROCEDURES: Partial (n = 12), full (8), and matched full and subsequently transected (10) thoracic limbs were collected. Bone volume CT images were acquired in three positions: extension (200° metacarpophalangeal angle), neutral (180°), and maximal flexion (110°). Mean translation and angular rotation of each DSB were recorded. Differences were determined with two-way ANOVA and post hoc Tukey's tests for pairwise comparisons; P value was set at < 0.05. RESULTS: Dorsal translation was significant during extension (1.4 ± 0.4 mm full limbs and 1.3 ± 0.2 mm partial limbs, P < 0.001). Distal translation was significant during extension (1.9 ± 0.4 mm full and 1.1 ± 0.4 mm partial) and flexion (5.4 ± 0.7 mm full and 6.22 ± 0.6 mm partial, P < 0.001). Rotation was significant (P < 0.001) about the mediolateral axis during extension (17.1° ± 1.4°) and flexion (2.6° ± 1.3°). Translation and rotation of the DSB were significantly different (P < 0.001) between full and partial limbs. CLINICAL RELEVANCE: This study provides the first quantification of translation and angular rotation of the DSB within the equine hoof. Partial limbs had significantly reduced movement compared to full limbs, suggesting that transection of flexor tendons alters distal thoracic limb kinematics. Further studies are required to determine if pathologic changes in the podotrochlear apparatus have an impact in clinical lameness outcomes.

Three-dimensional printed surgical guides for keratoma removal in horses using computed tomography or magnetic resonance imaging-based segmentation.

OBJECTIVE: To report the technique, surgical approach, and postoperative features in horses treated via a 3-dimensional (3D) printed guide-assisted keratoma resection created using computed tomography (CT) or magnetic resonance imaging (MRI)-based segmentation. ANIMALS: Five client-owned horses. STUDY DESIGN: Short case series. METHODS: Horses were placed under general anesthesia for imaging (CT and MRI) and underwent a second anesthesia for surgery. Two horses had guides created from CT-based imaging, 3 horses had guides created from MRI. Various sized nonarbored hole saws were used to create accurate and precise portals for keratoma removal. Surgical sites were managed until keratinized granulation tissue had formed and the defect was sealed with an artificial hoof wall patch. RESULTS: All keratomas were successfully removed as a single piece either intact with the hoof wall or easily extracted after the hoof wall portal was created in a surgical time between 20 and 90 min. All CT created guides fitted without issue; MRI-created guides required minor adjustments with a rotary device for proper fit. All cases had minor debridement adjacent to P3 and circumferential lamellar tissue. All horses returned to previous level of performance 2 to 4 months postoperatively. CONCLUSION: Use of 3D printed guides led to accurate targeting of keratomas with small surgical portals and short surgical times. Due to challenges with MRI-based segmentation, CT is preferred.

Three-dimensional printed guides for screw placement in equine navicular bones.

OBJECTIVE: To determine the influence of a custom 3D-printed guide for placement of cortical bone screws in the equine navicular bone. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Eight pairs of normal adult equine forelimbs. METHODS: A 3.5 × 55 mm cortical screw was placed in the longitudinal axis of each intact navicular bone. Screws were placed with a 3D-printed guide (3D) in one bone and with a traditional aiming device (AD) in the contralateral bone within each pair. Duration of surgery and the number of fluoroscopy images were compared between techniques. Screw placement was subjectively evaluated by gross examination and scored by three boarded veterinary surgeons. RESULTS: The use of a 3D-printed guide reduced the duration of surgery by 6.6 min (±1.5 min) compared to traditional screw placement (20.7 min ± 4.8 min, p < .01). Fewer peri-operative fluoroscopic images were obtained when the 3D guide was used (18 images ± 2.6 images vs. 40 images ± 5.1, p < .01). No difference was detected in navicular screw placement. CONCLUSION: The use of a 3D guide decreased the time required to place screws and the number of intraoperative images taken without affecting screw placement in intact navicular bones. CLINICAL RELEVANCE: 3D-printed guides can aid in the study, practice, and execution of surgical procedures reducing surgical time and radiation exposure throughout the operative period achieving similar results to those obtained with a conventional approach.

Use of Hausdorff Distance and Computer Modelling to Evaluate Virtual Surgical Plans with Three-Dimensional Printed Guides against Freehand Techniques for Navicular Bone Repair in Equine Orthopaedics.

OBJECTIVE: The aim of this study was to evaluate the surgical execution of a virtual surgical plan (VSP) with three-dimensional (3D) guides against a freehand approach in the equine navicular bone using an automated in silico computer analysis technique. STUDY DESIGN: Eight pairs of cadaveric forelimb specimens of adult horses were used in an ex vivo experimental study design with in silico modelling. Limbs received either a 3.5 mm cortical screw according to a VSP or using an aiming device. Using computed tomography and computer segmentation, a comparison was made between the executed screw and the planned screw using the Hausdorff distance (HD). RESULTS: Navicular bone mean HD registration error was -0.06 ± 0.29 mm. The VSP with 3D printing demonstrated significantly superior accuracy with a mean deviation of 1.19 ± 0.42 mm compared with aiming device group (3.53 ± 1.24 mm, p = 0.0018). The VSP group was 5.0 times more likely to result in a mean aberration of less than 1.0 mm (95% confidence interval, 0.62-33.4). A 3.5 mm screw with an optimal entry point can have a maximum deviation angle of 3.23 ± 0.07, 2.70 ± 0.06 and 2.37 ± 0.10 degrees in a proximal, dorsal and palmar direction respectively, prior to violating one of the cortical surfaces. CONCLUSION: Procedures performed using the 3D guides have a high degree of accuracy, with minimal mean deviations (<1 mm and <1 degree) of a VSP compared with those using the conventional aiming device. The use of VSP and the HD for evaluation of orthopaedic surgeries and outcome measures shows promise for simplifying and improving surgical accuracy.

Self-Complementary Adeno-Associated Virus-Mediated Interleukin-1 Receptor Antagonist Gene Delivery for the Treatment of Osteoarthritis: Test of Efficacy in an Equine Model.

The authors are investigating self-complementary adeno-associated virus (scAAV) as a vector for intra-articular gene-delivery of interleukin-1 receptor antagonist (IL-1Ra), and its therapeutic capacity in the treatment of osteoarthritis (OA). To model gene transfer on a scale proportional to the human knee, a frequent site of OA incidence, studies were focused on the joints of the equine forelimb. Using AAV2.5 capsid and equine IL-1Ra as a homologous transgene, a functional ceiling dose of ∼5 × 1012 viral genomes was previously identified, which elevated the steady state levels of eqIL-1Ra in synovial fluids by >40-fold over endogenous production for at least 6 months. Here, using an osteochondral fragmentation model of early OA, the functional capacity of scAAV.IL-1Ra gene-delivery was examined in equine joints over a period of 12 weeks. In the disease model, transgenic eqIL-1Ra expression was several fold higher than seen previously in healthy joints, and correlated directly with the severity of joint pathology at the time of treatment. Despite wide variation in expression, the steady-state eqIL-1Ra in synovial fluids exceeded that of IL-1 by >400-fold in all animals, and a consistent treatment effect was observed. This included a 30-40% reduction in lameness and ∼25% improvement in total joint pathology by both magnetic resonance imaging and arthroscopic assessments, which included reduced joint effusion and synovitis, and improved repair of the osteochondral lesion. No vector-related increase in eqIL-1Ra levels in blood or urine was noted. Cumulatively, these studies in the equine model indicate scAAV.IL-1Ra administration is reasonably safe and capable of sustained therapeutic IL-1Ra production intra-articularly in joints of human scale. This profile supports consideration for human testing in OA.

Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model.

Toward the treatment of osteoarthritis (OA), the authors have been investigating self-complementary adeno-associated virus (scAAV) for intra-articular delivery of therapeutic gene products. As OA frequently affects weight-bearing joints, pharmacokinetic studies of scAAV gene delivery were performed in the joints of the equine forelimb to identify parameters relevant to clinical translation in humans. Using interleukin-1 receptor antagonist (IL-1Ra) as a secreted therapeutic reporter, scAAV vector plasmids containing codon-optimized cDNA for equine IL-1Ra (eqIL-1Ra) were generated, which produced eqIL-1Ra at levels 30- to 50-fold higher than the native sequence. The most efficient cDNA was packaged in AAV2.5 capsid, and following characterization in vitro, the virus was injected into the carpal and metacarpophalangeal joints of horses over a 100-fold dose range. A putative ceiling dose of 5 × 1012 viral genomes was identified that elevated the steady-state eqIL-1Ra in the synovial fluids of injected joints by >40-fold over endogenous levels and was sustained for at least 6 months. No adverse effects were seen, and eqIL-1Ra in serum and urine remained at background levels throughout. Using the 5 × 1012 viral genome dose of scAAV, and green fluorescent protein as a cytologic marker, the local and systemic distribution of vector and transduced cells following intra-articular injection scAAV.GFP were compared in healthy equine joints and in those with late-stage, naturally occurring OA. In both cases, 99.7% of the vector remained within the injected joint. Strikingly, the pathologies characteristic of OA (synovitis, osteophyte formation, and cartilage erosion) were associated with a substantial increase in transgenic expression relative to tissues in healthy joints. This was most notable in regions of articular cartilage with visible damage, where foci of brilliantly fluorescent chondrocytes were observed. Overall, these data suggest that AAV-mediated gene transfer can provide relatively safe, sustained protein drug delivery to joints of human proportions.

Effect of lidocaine on inflammation in equine jejunum subjected to manipulation only and remote to intestinal segments subjected to ischemia.

OBJECTIVE To examine effects of continuous rate infusion of lidocaine on transmural neutrophil infiltration in equine intestine subjected to manipulation only and remote to ischemic intestine. ANIMALS 14 healthy horses. PROCEDURES Ventral midline celiotomy was performed (time 0). Mild ischemia was induced in segments of jejunum and large colon. A 1-m segment of jejunum was manipulated by massaging the jejunal wall 10 times. Horses received lidocaine (n = 7) or saline (0.9% NaCl) solution (7) throughout anesthesia. Biopsy specimens were collected and used to assess tissue injury, neutrophil influx, cyclooxygenase expression, and hypoxia-inducible factor 1α (HIF-1α) expression at 0, 1, and 4 hours after manipulation and ischemia. Transepithelial resistance (TER) and mannitol flux were measured by use of Ussing chambers. RESULTS Lidocaine did not consistently decrease neutrophil infiltration in ischemic, manipulated, or control tissues at 4 hours. Lidocaine significantly reduced circular muscle and overall scores for cyclooxygenase-2 expression in manipulated tissues. Manipulated tissues had significantly less HIF-1α expression at 4 hours than did control tissues. Mucosa from manipulated and control segments obtained at 4 hours had lower TER and greater mannitol flux than did control tissues at 0 hours. Lidocaine did not significantly decrease calprotectin expression. Severity of neutrophil infiltration was similar in control, ischemic, and manipulated tissues at 4 hours. CONCLUSIONS AND CLINICAL RELEVANCE Manipulated jejunum did not have a significantly greater increase in neutrophil infiltration, compared with 4-hour control (nonmanipulated) jejunum remote to sites of manipulation, ischemia, and reperfusion. Lidocaine did not consistently reduce neutrophil infiltration in jejunum.

Response to early repeat celiotomy in horses after a surgical treatment of jejunal strangulation.

OBJECTIVE: To determine the outcome after early repeat celiotomy in horses operated for jejunal strangulation. STUDY DESIGN: Retrospective case series. ANIMALS: Horses (n = 22) that underwent repeat celiotomy for postoperative reflux (POR) and/or postoperative colic (POC) that did not improve within 48 hours from onset after initial surgical treatment of strangulating jejunal lesions by jejunojejunostomy (n = 14) or no resection (n = 8). METHODS: Medical records were reviewed for clinical signs, duration of signs before repeat surgery, surgical findings and treatment, and outcome. Survival was documented by phone call at long-term follow-up. The influence of POC and POR on timing of surgery were analyzed. Long-term survival was examined by Kaplan-Meier analyses. RESULTS: Repeat celiotomy was performed at a median of 57 hours after initial surgery and 16.5 hours from onset of signs, and earlier in horses with POC compared with POR (P < .05). A total of 3/22 horses were euthanatized under anesthesia. A total of 9 of 11 horses with initial jejunojejunostomy required resection of the original anastomosis due to anastomotic complications. In 8 horses without resection, second surgery included resection (4) or decompression (4). Repeat celiotomy was successful in 13/16 horses with POR. Repeat celiotomy eliminated POC in all horses (n = 9). A total of 19 horses were recovered from anesthesia and all survived to discharge. Incisional infections were diagnosed in 13/17 horses where both surgeries were performed through the same ventral median approach, and hernias developed in 4/13 infected incisions. Median survival time was 90 months. CONCLUSION: Repeat celiotomy can eliminate signs of POR and/or POC, and the additional surgery does not appear to aggravate POR. Criteria for repeat celiotomy in this study could provide guidelines for managing POC and POR after surgery for jejunal strangulation.

MAGNETIC RESONANCE IMAGING SCORING OF AN EXPERIMENTAL MODEL OF POST-TRAUMATIC OSTEOARTHRITIS IN THE EQUINE CARPUS.

Magnetic resonance imaging (MRI) is the most sensitive imaging modality to detect the early changes of osteoarthritis. Currently, there is no quantifiable method to tract these pathological changes over time in the horse. The objective of this experimental study was to characterize the progression of MRI changes in an equine model of post-traumatic osteoarthritis using a semiquantitative scoring system for whole-organ evaluation of the middle carpal joint. On day 0, an osteochondral fragment was created in one middle carpal joint (OCI) and the contralateral joint (CON) was sham-operated in 10 horses. On day 14, study horses resumed exercise on a high-speed treadmill until the completion of the study (day 98). High-field MRI examinations were performed on days 0 (preosteochondral fragmentation), 14, and 98 and scored by three blinded observers using consensus agreement. Images were scored based on 15 independent articular features, and scores were compared between and within-groups. On days 14 and 98, OCI joints had significantly (P ≤ 0.05) higher whole-organ median scores (29.0 and 31.5, respectively), compared to CON joints (21.5 and 20.0, respectively). On day 14, OCI joints showed significant increases in high-signal bone lesion scores, and osteochondral fragment number and size. On day 98, high-signal bone lesion, low-signal bone lesion, osteophyte formation, cartilage signal abnormality, subchondral bone irregularity, joint effusion, and synovial thickening scores were significantly increased in OCI joints. Study results suggest that the MRI whole-organ scoring system reported here may be used to identify onset and progression of pathological changes following osteochondral injury.

Effect of large colon ischemia and reperfusion on concentrations of calprotectin and other clinicopathologic variables in jugular and colonic venous blood in horses.

OBJECTIVE: To determine the effect of large colon ischemia and reperfusion on concentrations of the inflammatory neutrophilic protein calprotectin and other clinicopathologic variables in jugular and colonic venous blood in horses. ANIMALS: 6 healthy horses. PROCEDURES: Horses were anesthetized, and ischemia was induced for 1 hour followed by 4 hours of reperfusion in a segment of the pelvic flexure of the large colon. Blood samples were obtained before anesthesia, before induction of ischemia, 1 hour after the start of ischemia, and 1, 2, and 4 hours after the start of reperfusion from jugular veins and veins of the segment of the large colon that underwent ischemia and reperfusion. A sandwich ELISA was developed for detection of equine calprotectin. Serum calprotectin concentrations and values of blood gas, hematologic, and biochemical analysis variables were determined. RESULTS: Large colon ischemia caused metabolic acidosis, a significant increase in lactate and potassium concentrations and creatine kinase activities, and a nonsignificant decrease in glucose concentrations in colonic venous blood samples. Values of these variables after reperfusion were similar to values before ischemia. Ischemia and reperfusion induced activation of an inflammatory response characterized by an increase in neutrophil cell turnover rate in jugular and colonic venous blood samples and calprotectin concentrations in colonic venous blood samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested that large colon ischemia and reperfusion caused local and systemic inflammation in horses. Serum calprotectin concentration may be useful as a marker of this inflammatory response.

Effects of ischemia and reperfusion on production of nitrotyrosine, activation of eosinophils, and apoptosis in the large colonic mucosa of horses.

OBJECTIVE: To assess the effects of ischemia and reperfusion on indicators of oxidative stress, activation of eosinophils, and apoptosis in the large colonic mucosa of horses. ANIMALS: 40 horses. PROCEDURES: In 1 or two 20-cm-long segments of the pelvic flexure, ischemia was induced for 1 or 2 hours followed by no reperfusion or 30 minutes and 18 hours of reperfusion in anesthetized horses. Mucosal specimens were collected before (controls; n = 20 horses) and after each period of ischemia, and full-thickness tissue samples were collected after each period of reperfusion. Sections of colonic tissues were stained for histomorphometric analysis or assessment of eosinophil accumulation. Nitrotyrosine was identified immunohistochemically, and severity of apoptosis was determined via the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method. RESULTS: Numbers of mucosal eosinophils were similar before induction of ischemia, after ischemia, and after ischemia-reperfusion. Eosinophil nitrotyrosine production increased significantly during ischemia and continued through 30 minutes of reperfusion; production was decreased at 18 hours of reperfusion but remained greater than that of the controls. In other leukocytes, nitrotyrosine generation peaked at 1 hour of ischemia and again at 18 hours of reperfusion. Compared with control findings, epithelial apoptosis increased gradually at 1 through 2 hours of ischemia with no further progression after reperfusion. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that resident eosinophils in the large colon of horses react to mucosal injury from ischemia and reperfusion and may undergo oxidative stress under those conditions. Epithelial apoptosis could contribute to tissue damage.

In vitro and in vivo responses of mucosa from the large colon of horses to ischemia and reperfusion.

OBJECTIVE: To induce ischemia and reperfusion injury in the large colon mucosa of horses in vivo and evaluate the recovery and effects of components of an organ transplant solution on mucosal recovery in vitro. ANIMALS: 6 healthy horses. PROCEDURES: Horses were anesthetized, and ischemia was induced for 60 minutes in the pelvic flexure, which was followed by reperfusion for 240 minutes. Ischemic (n = 4 horses), reperfused (6), and adjacent control (6) colonic mucosae were isolated for in vitro testing and histologic examinations. Tissues were mounted in Ussing chambers with plain Krebs Ringer bicarbonate (KRB), KRB with N-acetylcysteine (NAC), or KRB with a modified organ transplant solution (MOTS). Transepithelial electrical resistance (TER) and mannitol flux were used to assess mucosal integrity. Data were analyzed by use of ANOVA and Kruskal-Wallis tests. RESULTS: The TER in reperfused tissues was similar to the TER in control tissues and greater than the TER in ischemic tissues, which was consistent with morphological evidence of recovery in reperfused tissues. Mannitol flux was greater in ischemic tissues than in reperfused tissues. The TER and mannitol flux were not significantly affected by incubation of mucosa with NAC or MOTS. CONCLUSIONS AND CLINICAL RELEVANCE: Ischemia induced during the brief period allowed rapid mucosal repair and complete recovery of tissue barrier properties during reperfusion. Therefore, reperfusion injury was not observed for this method of ischemic damage in equine colonic mucosa.

Magnetic resonance imaging findings in horses with septic arthritis.

Fourteen horses with septic arthritis underwent high-field (1.5 T) magnetic resonance imaging (MRI). Septic arthritis was diagnosed based on results from historical and clinical findings, synovial fluid analyses and culture, and radiographic, ultrasonographic, arthroscopic, and histopathologic findings. MR findings included diffuse hyperintensity within bone and extracapsular tissue on fat-suppressed images in 14/14 horses (100%), joint effusion, synovial proliferation, and capsular thickening in 13/14 horses (93%), bone sclerosis in 11/14 horses (79%), and evidence of cartilage and subchondral bone damage in 8/14 horses (57%). Intravenous gadolinium was administered to five of the 14 horses and fibrin deposition was noted in all horses. Other findings after gadolinium administration included synovial enhancement in 4/5 (80%) horses, and bone enhancement in 1/5 (20%) horses. The MR findings of septic arthritis in horses were consistent with those reported in people. MRI may allow earlier and more accurate diagnosis of septic arthritis in horses as compared with other imaging modalities, especially when the clinical diagnosis is challenging. It also provides additional information not afforded by other methods that may influence and enhance treatment.

Expression of cyclooxygenase-1 and -2 in the left dorsal colon after different durations of ischemia and reperfusion in horses.

OBJECTIVE-To identify expression and localization of cyclooxygenase (COX)-1 and COX-2 in healthy and ischemic-injured left dorsal colon of horses. SAMPLE POPULATION-Left dorsal colon tissue samples from 40 horses. PROCEDURES-Tissue samples that were used in several related studies on ischemia and reperfusion were evaluated. Samples were collected during anesthesia, before induction of ischemia, and following 1 hour of ischemia, 1 hour of ischemia and 30 minutes of reperfusion, 2 hours of ischemia, 2 hours of ischemia and 30 minutes of reperfusion, and 2 hours of ischemia and 18 hours of reperfusion. Histomorphometric analyses were performed to characterize morphological injury. Immunohistochemical analyses were performed to characterize expression and localization of COX-1 and COX-2. RESULTS-COX-1 and COX-2 were expressed in control tissues before ischemia was induced, predominantly in cells in the lamina propria. Ischemic injury significantly increased expression of COX-2 in epithelial cells on the colonic surface and in crypts. A similar significant increase of COX-1 expression was seen in the epithelial cells. CONCLUSIONS AND CLINICAL RELEVANCE-On the basis of information on the role of COX-2, upregulation of COX-2 in surface epithelium and crypt cells following ischemic injury in equine colon may represent an early step in the repair process.

Effects of flunixin meglumine on recovery of colonic mucosa from ischemia in horses.

OBJECTIVE: To examine the effects of flunixin meglumine (FM) on recovery of colonic mucosa from experimentally induced ischemia in horses. ANIMALS: 14 research horses. PROCEDURES: Ischemia was induced in the colons of anesthetized horses for 2 hours. Afterward, horses received saline (0.9% NaCl) solution (12 mL, IV, q 12 h; n = 7) or FM (1.1 mg/kg, IV, q 12 h; 7) and were allowed to recover for 18 hours after termination of the ischemic event. Postoperative pain scores were recorded every 4 hours throughout the recovery period. At the end of the recovery period, horses were anesthetized, and ischemic and nonischemic segments of colonic mucosa were harvested for histologic evaluation, western blot analysis, and in vitro assessment of transepithelial electric resistance (TER) and transmucosal flux of tritium-labeled (3H-) mannitol. Horses were then euthanatized. RESULTS: Flunixin meglumine significantly lowered pain scores at the first postoperative recording. There were no significant differences between treatment with saline solution and FM in any of the measurements for TER, 3H-mannitol flux, histomorphometric variables, neutrophil infiltration (detected via calprotectin immunostaining), and expressions of cyclooxygenase-1 and -2. After both treatments, TER declined significantly in nonischemic tissues in vitro, whereas it increased significantly in ischemic-injured tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Flunixin meglumine did not affect recovery of equine colonic mucosa from ischemic injury, and continued use in horses with colonic ischemia is therefore justified.

The influence of a novel organ perfusion solution on early graft function in canine renal autotransplantation.

OBJECTIVE: To evaluate the influence of a kidney perfusion solution on early graft function in dogs. STUDY DESIGN: Experimental, randomized study. ANIMALS: Intact adult male mongrel dogs (n=12). METHODS: Dogs had renal autograft transplantation without ureteroneocystotomy with contralateral nephrectomy. Kidney graft flushing with a novel organ perfusion solution was compared with flushing with saline (0.9% NaCl) solution. Serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations were measured daily posttransplant for 7 days. Ultrasound-guided renal biopsy was performed on postoperative day 1 for electron microscopic evaluation. Dogs were euthanatized on day 7. RESULTS: All dogs completed the study. Cr and BUN concentrations of the saline group were significantly greater than the organ perfusion solution group on each postoperative day (P=.01 for S Cr; P=.001 for BUN). Electron micrographs of nuclei and mitochondria from convoluted proximal tubule cells indicated profound ultrastructural disruptions in the saline group and mild ultrastructural disruptions in the organ perfusion solution group. CONCLUSION: Flushing solution composition can influence early graft function in live donor kidney transplantation. CLINICAL RELEVANCE: Use of a specialized flushing solution can improve early graft function in canine kidney transplantation, independent of antigen-mediated events.

Analysis of sodium carboxymethylcellulose administration and related factors associated with postoperative colic and survival in horses with small intestinal disease.

OBJECTIVE: To analyze the effect of the intraoperative use of sodium carboxymethylcellulose (CBMC) and related perioperative factors on postoperative colic and survival in horses that had abdominal surgery for colic. STUDY DESIGN: Retrospective study. ANIMALS: Horses (n=203) that had surgery for small intestinal disease; 33 horses had intraoperative administration of CBMC. METHODS: Information was obtained from medical records for 170 horses that had surgery for colic before use of CBMC and 33 horses that had intraoperative CBMC. Kaplan-Meier survival curves were used to estimate median survival time and a Cox proportional hazards model was used to estimate the hazard ratio for the effect of CBMC and other perioperative variables on survival. RESULTS: Seventy-five percent of horses administered CBMC survived to 180 days, whereas 75% of untreated horses survived 8 days (median survival time=18 days). Horses not administered CBMC were twice as likely to die compared with horses administered CBMC. Horses that had postoperative ileus (POI) were 1.4 times more likely to die than horses without ileus. Similarly, horses with signs of colic after surgery were 1.3 times more likely to die than horses without postoperative signs of colic. CONCLUSIONS: CBMC administration is seemingly protective against death and prolongs survival when used intraoperatively in horses with small intestine disease, particularly horses with postoperative colic or POI. Both POI and colic increased risk of death after surgery. CLINICAL RELEVANCE: Intraoperative administration of CBMC in horses that have surgery for small intestinal disease may improve survival, possibly by reducing early adhesion formation.

Diagnosis and treatment of septic arthritis.

Septic arthritis (SA) is a common orthopedic condition encountered in horses that are presented to equine veterinarians. Successful out-come is dependent on prompt and thorough evaluation and treatment. This article briefly reviews the pathophysiology, outlines diagnostics, describes treatment options and prognostics, and discusses current research in diagnosis and treatment of SA.