Pharmacokinetics and Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses.

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, 1.33, 1.66, 2, 2.33, 2.66, 3, 3.5, 4, 5, 6, 8, 12, 24, 32, and 48 h post administration. CFZ was quantified using UHPLC coupled to tandem quadrupole mass spectrometry (UHPLC-MS/MS). A non-compartmental analysis revealed key pharmacokinetic parameters, including a median Tmax of 7 h, a Cmax of 2350 ng/mL, and a t1/2Z of 28.5 h. CFZ treatment reduced glucose (AUCGLU, p = 0.001) and insulin (AUCINS, p = 0.04) response to a graded glucose infusion administered 5 h after treatment. This indicates a rapid onset of action following a single dose in healthy Icelandic horses. No obvious adverse effects related to the treatment were observed.

Objective movement asymmetry in horses is comparable between markerless technology and sensor-based systems.

BACKGROUND: A markerless artificial intelligence (AI) system for lameness detection has recently become available but has not been extensively compared with commonly used inertial measurement unit (IMU) systems for detecting asymmetry under field conditions. OBJECTIVE: Comparison of classification of asymmetric limbs under field conditions and comparison of normalised asymmetry data using a markerless AI system (SleipAI; recorded on a tripod mounted iPhone 14pro [SL]); the Equinosis Q Lameness Locator (LL); the EquiMoves (EM); and subjective evaluation (SE). STUDY DESIGN: Descriptive clinical study. METHODS: Straight line trot data were collected from 52 client-owned horses in regular training. Limbs were categorised as symmetric or asymmetric. Number of analysed strides were compared with Wilcoxon's each pairs test. Inter-rater reliability in classification of asymmetric limbs was assessed with Light's Kappa. Bland Altman analysis of normalised asymmetry data was performed. RESULTS: Data from 41 horses were included. Most horses showed mild asymmetry. The EM analysed significantly more strides than the other systems, both for forelimbs and for hindlimbs (53 ± 11 strides for both, respectively; p < 0.006). The LL analysed significantly more hindlimbs strides (45 ± 13) than the SL (27 ± 6; p < 0.001). Moderate inter-rater agreement for asymmetry classification was found between systems (k = 0.59 forelimbs; 0.44 hindlimbs); agreement decreased when including the SE. For the normalised asymmetry data, the strongest agreement was found between the two IMU systems. MAIN LIMITATIONS: Horses were assessed during straight-line trot only. CONCLUSIONS: The objective systems were comparable in classification of asymmetric limbs under field conditions when using defined asymmetry thresholds. Discrepancies stemmed largely from the imposed thresholds (i.e., systems largely identified same-side asymmetry). Overall, the strongest agreement was found between LL and EM. The SL analysed significantly fewer hindlimb strides than the LL and EM which could represent a limitation of the Sleip AI.

Osteochondrosis in the central and third tarsal bones of young horses.

Recently, the central and third tarsal bones of 23 equine fetuses and foals were examined using micro-computed tomography. Radiological changes, including incomplete ossification and focal ossification defects interpreted as osteochondrosis, were detected in 16 of 23 cases. The geometry of the osteochondrosis defects suggested they were the result of vascular failure, but this requires histological confirmation. The study aim was to examine central and third tarsal bones from the 16 cases and to describe the tissues present, cartilage canals, and lesions, including suspected osteochondrosis lesions. Cases included 9 males and 7 females from 0 to 150 days of age, comprising 11 Icelandic horses, 2 standardbred horses, 2 warmblood riding horses, and 1 coldblooded trotting horse. Until 4 days of age, all aspects of the bones were covered by growth cartilage, but from 105 days, the dorsal and plantar aspects were covered by fibrous tissue undergoing intramembranous ossification. Cartilage canal vessels gradually decreased but were present in most cases up to 122 days and were absent in the next available case at 150 days. Radiological osteochondrosis defects were confirmed in histological sections from 3 cases and consisted of necrotic vessels surrounded by ischemic chondronecrosis (articular osteochondrosis) and areas of retained, morphologically viable hypertrophic chondrocytes (physeal osteochondrosis). The central and third tarsal bones formed by both endochondral and intramembranous ossification. The blood supply to the growth cartilage of the central and third tarsal bones regressed between 122 and 150 days of age. Radiological osteochondrosis defects represented vascular failure, with chondrocyte necrosis and retention, or a combination of articular and physeal osteochondrosis.

Cytokine enrichment in equine conditioned serum is not reliant on incubation in specialized containers.

Autologous conditioned serum (ACS), i.e serum enriched with anti-inflammatory cytokines and growth factors, is a popular orthobiologic therapy used in equine practice. Costly specialized tubes containing glass beads are commonly used for ACS production. The objective of this in vitro study was to compare cytokine and growth factor levels in equine serum after incubation in three different tubes: commercial plastic ACS tubes (COMM); sterile 50 ml plastic centrifugation tubes (CEN); and 10 ml plastic vacutainer tubes (VAC). Blood from 15 healthy horses was incubated in the different tubes at 37°C for 22-24 h. The concentration of IL-1ß, IL-1Ra, IL-10, IGF-1 and PDGF-BB was determined by ELISA and compared between tubes. There was no difference in concentration of IL-1Ra and IGF-1 between CEN and COMM. PDGF-BB was higher in CEN vs. COMM (P < 0.0001). IL-1Ra and PDGF-BB was higher (P < 0.005 and P = 0.02, respectively) whereas IGF-1 was lower in VAC (P < 0.003) vs. the other tubes. The centrifuge tube performed similarly to the commercial ACS tube in cytokine and growth factor enrichment and has the potential to dramatically reduce the cost of ACS treatment. Cytokine enrichment of equine serum does not require blood incubation in specialized ACS containers.

Conditioned serum in vitro treatment of chondrocyte pellets and osteoarthritic explants.

BACKGROUND: Autologous conditioned serum (ACS) is used to treat osteoarthritis in horses, although its effects are not fully investigated. OBJECTIVES: To investigate the effects of equine serum and conditioned serum on chondrocytes stimulated with interleukin (IL)-1ß and cartilage explants with mild osteoarthritis. STUDY DESIGN: In vitro experimental study. METHODS: The effect of three different serum preparations (unincubated control [PS], serum incubated 24 h [PS24h] and serum incubated 24 h in ACS containers [PCS]) pooled from lame horses were tested in two in vitro models. IL-1ß and IL-1 receptor antagonist (IL-1Ra) concentrations were measured in all sera. In model 1, chondrocyte pellet cultures were stimulated with IL-1ß prior to treatment with the serum preparations for 2 and 48 h. Microarray, polymerase chain reaction, and matrix metallopeptidase-13 analyses were performed. In model 2, cartilage explants from horses with structural osteoarthritis were treated with PS or PCS on days 0, 6 and 12, or left untreated, and evaluated at day 24 using the OARSI grading scale for histological evaluation of articular cartilage. RESULTS: The IL-1Ra concentration in PS24h and PCS was significantly higher than in PS. In model 1, inflammation- and cartilage matrix degradation-related genes were upregulated after 48 h in all treatment groups versus untreated controls. Cartilage matrix molecules, aggrecan and collagens, were downregulated in PS24h- and PCS-treated pellets versus untreated controls. Growth factor signalling genes were upregulated-FGF7 in all treatment groups, BMP2 in PS24h-, and INHBA in PCS-treated-compared with untreated controls. In model 2, the OARSI score at day 24 was not significantly different between treatment groups. MAIN LIMITATIONS: Results from in vitro models cannot be directly translated to in vivo situations. CONCLUSIONS: In vitro treatment with conditioned serum did not alleviate IL-1ß-induced responses in chondrocyte pellets or lead to morphological improvement in osteoarthritic cartilage explants.

HISTORIAL: Suero autólogo acondicionado (ACS) es usado para tartar osteoartritis en caballos, aunque sus efectos no han sido completamente investigados. OBJETIVOS: Investigar los efectos de suero equino y suero acondicionado en condrocitos estimulados con interleukina (IL)-1ß y explantes de cartílago con osteoartritis leve. DISEÑO DEL ESTUDIO: Estudio experimental in vitro. MÉTODOS: El efecto de tres preparaciones séricas diferentes (control no incubado (PS), suero incubado 24 h (PS24h), y suero incubado 24 h en frascos ACS (PCS)) combinados y obtenidos de caballos cojos fueron probados en dos modelos in vitro. Las concentraciones de IL-1ß y de receptor antagonista de IL-1 (IL-1Ra) fueron medidas en todos los sueros. En el modelo 1, los cultivos de pellets de condrocitos fueron estimulados con IL-1ß antes de ser tratados con las preparaciones séricas durante 2 y 48 h. Se realizaron análisis de micromatrices, reacciones de polimerasa en cadena y de matriz de metalopeptidasa-13. En el modelo 2, explantaciones de cartílago proveniente de caballos con osteoartritis estructural fueron tratados con PS o PCS en los días 0, 6 y 12, o dejados sin tartar, y evaluados al día 24 usando la escala de graduación OARSI para evaluación histológica de cartílago articular. RESULTADOS: La concentración de IL-1Ra en PS24h y PCS fue significativamente mayor que en PS. En el modelo 1, los genes relacionados a la inflamación y a la degradación de la matriz cartilaginosa estaban aumentados después de 48 h en todos los grupos tratados en comparación a los controles no tratados. Las moléculas de matriz cartilaginosa, agrecanos y colágenos estaban disminuidos en los pellets PS24h y PCS versus los controles no tratados. Los genes de señales de factores de crecimiento FGF7 estaban aumentados en todos los grupos tratados, BMP2 en PS24h y INHBA in PCS en comparación con los controles no tratados. En el modelo 2, la escala OARSI al día 24 no fue significativamente distinta entre los grupos de tratamientos. LIMITACIONES PRINCIPALES: Los resultados de modelos in vitro no pueden ser directamente aplicados a situaciones in vivo. CONCLUSIONES: El tratamiento in vitro con suero acondicionado no alivió las respuestas inducidas por IL-1ß en pellets de condrocitos o llevo a mejoramiento morfológico en explantes de cartílago con osteoartritis.

Conditioned serum in vitro treatment of chondrocyte pellets and osteoarthritic explants.

BACKGROUND: Autologous conditioned serum (ACS) is used to treat osteoarthritis in horses, although its effects are not fully investigated. OBJECTIVES: To investigate the effects of equine serum and conditioned serum on chondrocytes stimulated with interleukin (IL)-1ß and cartilage explants with mild osteoarthritis. STUDY DESIGN: In vitro experimental study. METHODS: The effect of three different serum preparations (unincubated control [PS], serum incubated 24 h [PS24h], and serum incubated 24 h in ACS containers [PCS]) pooled from lame horses were tested in two in vitro models. IL-1ß and IL-1 receptor antagonist (IL-1Ra) concentrations were measured in all sera. In model 1, chondrocyte pellet cultures were stimulated with IL-1ß prior to treatment with the serum preparations for 2 and 48 h. Microarray, polymerase chain reaction, and matrix metallopeptidase-13 analyses were performed. In model 2, cartilage explants from horses with structural osteoarthritis were treated with PS or PCS on days 0, 6, and 12, or left untreated, and evaluated at day 24 using the OARSI grading scale for histological evaluation of articular cartilage. RESULTS: The IL-1Ra concentration in PS24h and PCS was significantly higher than in PS. In model 1, inflammation- and cartilage matrix degradation-related genes were upregulated after 48 h in all treatment groups versus untreated controls. Cartilage matrix molecules, aggrecan and collagens, were downregulated in PS24h- and PCS- treated pellets versus untreated controls. Growth factor signalling genes were upregulated-FGF7 in all treatment groups, BMP2 in PS24h-, and INHBA in PCS-treated- compared with untreated controls. In model 2, the OARSI score at day 24 was not significantly different between treatment groups. MAIN LIMITATIONS: Results from in vitro models cannot be directly translated to in vivo situations. CONCLUSIONS: In vitro treatment with conditioned serum did not alleviate IL-1ß-induced responses in chondrocyte pellets or lead to morphological improvement in osteoarthritic cartilage explants.

Radiological, vascular osteochondrosis occurs in the distal tarsus, and may cause osteoarthritis.

BACKGROUND: Osteochondrosis occurs due to failure of the blood supply to growth cartilage. Osteochondrosis lesions have been identified in small tarsal bones and suggested to cause distal tarsal osteoarthritis; however, it has not been determined whether distal tarsal osteochondrosis lesions were the result of vascular failure. OBJECTIVES: To perform post-mortem arterial perfusion and micro-computed tomography (CT) of the central (CTB) and third tarsal bones (TIII) of fetuses and foals up to 5 months old, to describe tarsal development and any lesions detected. STUDY DESIGN: Descriptive, nonconsecutive case series. METHODS: Twenty-three animals that died or were euthanased from 228 days of gestation to 5 months old were collected, comprising two fetuses and nine foals of miscellaneous breeds and 12 Icelandic Horse foals, a breed with high prevalence of distal tarsal osteoarthritis. One hindlimb from each foal was perfused arterially with barium, and the CTB and TIII were examined with micro-CT. RESULTS: Perfusion yielded partial information from 41% of the animals. The CTB and TIII were supplied by nutrient arteries and perichondrial vessels with vertical, transverse and circumferential configurations. Fourteen of the 23 (61%) animals had focal defects in the ossification front, that is, radiological osteochondrosis. The majority of lesions matched the configuration and development of vertical vessels. Additionally, full-thickness, cylindrical defects matched transverse vessels, and the long axes of some dorsal lesions matched circumferential vessels. MAIN LIMITATIONS: Lack of histological validation. CONCLUSIONS: Post-mortem perfusion was poor for examination of the blood supply to the growth cartilage of the CTB and TIII. Radiological osteochondrosis lesions were compatible with vascular failure because they were focal, and because lesion geometry matched vessel configuration. The relationship between osteochondrosis and distal tarsal osteoarthritis warrants further investigation.

Outcome analysis of 95 harness racehorses with confirmed dorsal displacement of the soft palate treated with laryngeal tie-forward surgery.

BACKGROUND: The laryngeal tie-forward (LTF) procedure is commonly used to treat intermittent dorsal displacement of the soft palate (iDDSP). There is a wide range in reported efficacy of treating horses with and without a definitive diagnosis of iDDSP. OBJECTIVES: To evaluate the racing performance of harness racehorses in which iDDSP had been definitely diagnosed and treated solely with the LTF procedure. STUDY DESIGN: Retrospective case series. METHODS: Ninety-five harness racehorses were treated with LTF for confirmed iDDSP. A definite diagnosis of iDDSP was made with high-speed treadmill or overground endoscopy. Upper respiratory tract (URT) disorders, short-term complications, and horses returning for recurrence of URT problems were recorded. Performance before and after LTF was assessed by reviewing career race records and comparing performance index (PI), and racing speed marks from the baseline, preoperative, and postoperative periods. The effect of basihyoid-cricoid (BC) net distance shortened on racing performance was assessed. RESULTS: Postoperatively, PI increased in 36/54 (67%, 95% CI 54%-79%) of experienced racehorses, and 44/67 (66%, 54%-77%) established or improved their racing speed mark relative to the preoperative period. As a group, PI decreased by a mean (SE) of 0.9 (0.17) points (P < .001) prior to diagnosis/surgery. Postoperatively, PI increased by 0.5 (0.16) points (P = .003), and racing speed improved by 0.83 (0.22) s (P < .001). Twenty-five percent (17%-34%) and 49% (39%-60%) of horses did not demonstrate a decline in PI and racing speed prior to diagnosis, respectively. Net BC distance shortening did not affect performance postoperatively. Twenty of 95 horses (21%, 13%-29%) had confirmed recurrence of iDDSP 46-708 days postoperatively. MAIN LIMITATIONS: Not all horses were evaluated with exercising endoscopy postoperatively. Racehorses inevitably develop other racing-related problems which confound studies of this nature. CONCLUSIONS: This study provides scientific support for the use of LTF to treat iDDSP in harness racehorses although iDDSP seems to affect harness racehorses differently as individuals.

Human-relevant near-organ neuromodulation of the immune system via the splenic nerve.

Neuromodulation of immune function by stimulating the autonomic connections to the spleen has been demonstrated in rodent models. Consequently, neuroimmune modulation has been proposed as a new therapeutic strategy for the treatment of inflammatory conditions. However, demonstration of the translation of these immunomodulatory mechanisms in anatomically and physiologically relevant models is still lacking. Additionally, translational models are required to identify stimulation parameters that can be transferred to clinical applications of bioelectronic medicines. Here, we performed neuroanatomical and functional comparison of the mouse, rat, pig, and human splenic nerve using in vivo and ex vivo preparations. The pig was identified as a more suitable model of the human splenic innervation. Using functional electrophysiology, we developed a clinically relevant marker of splenic nerve engagement through stimulation-dependent reversible reduction in local blood flow. Translation of immunomodulatory mechanisms were then assessed using pig splenocytes and two models of acute inflammation in anesthetized pigs. The pig splenic nerve was shown to locally release noradrenaline upon stimulation, which was able to modulate cytokine production by pig splenocytes. Splenic nerve stimulation was found to promote cardiovascular protection as well as cytokine modulation in a high- and a low-dose lipopolysaccharide model, respectively. Importantly, splenic nerve-induced cytokine modulation was reproduced by stimulating the efferent trunk of the cervical vagus nerve. This work demonstrates that immune responses can be modulated by stimulation of spleen-targeted autonomic nerves in translational species and identifies splenic nerve stimulation parameters and biomarkers that are directly applicable to humans due to anatomical and electrophysiological similarities.

Splenic Nerve Neuromodulation Reduces Inflammation and Promotes Resolution in Chronically Implanted Pigs.

Neuromodulation of the immune system has been proposed as a novel therapeutic strategy for the treatment of inflammatory conditions. We recently demonstrated that stimulation of near-organ autonomic nerves to the spleen can be harnessed to modulate the inflammatory response in an anesthetized pig model. The development of neuromodulation therapy for the clinic requires chronic efficacy and safety testing in a large animal model. This manuscript describes the effects of longitudinal conscious splenic nerve neuromodulation in chronically-implanted pigs. Firstly, clinically-relevant stimulation parameters were refined to efficiently activate the splenic nerve while reducing changes in cardiovascular parameters. Subsequently, pigs were implanted with a circumferential cuff electrode around the splenic neurovascular bundle connected to an implantable pulse generator, using a minimally-invasive laparoscopic procedure. Tolerability of stimulation was demonstrated in freely-behaving pigs using the refined stimulation parameters. Longitudinal stimulation significantly reduced circulating tumor necrosis factor alpha levels induced by systemic endotoxemia. This effect was accompanied by reduced peripheral monocytopenia as well as a lower systemic accumulation of CD16+CD14high pro-inflammatory monocytes. Further, lipid mediator profiling analysis demonstrated an increased concentration of specialized pro-resolving mediators in peripheral plasma of stimulated animals, with a concomitant reduction of pro-inflammatory eicosanoids including prostaglandins. Terminal electrophysiological and physiological measurements and histopathological assessment demonstrated integrity of the splenic nerves up to 70 days post implantation. These chronic translational experiments demonstrate that daily splenic nerve neuromodulation, via implanted electronics and clinically-relevant stimulation parameters, is well tolerated and is able to prime the immune system toward a less inflammatory, pro-resolving phenotype.

Non-banked curved tracks influence movement symmetry in two-year-old Standardbred trotters.

BACKGROUND: Little is known regarding how trotting through curves affects locomotion symmetry in Standardbred trotters. OBJECTIVES: To investigate differences in objectively measured Standardbred trotter vertical motion symmetry between straight and non-banked, curved sections of oval trotting tracks during exercise warm-up, using a wireless inertial measurement unit (IMU) system. STUDY DESIGN: Cross-sectional, observational study. METHODS: Sixteen horses were included. Mixed models were used to assess associations between symmetry, track segment (straight vs curve) and stride duration. RESULTS: Significant results for forelimb parameters were dependent on interactions between track segments and stride duration. At mean stride duration (0.611 second), during the curved track segment horses showed a lower maximum vertical position of the head after push-off of the outside forelimb (estimate -2.3 mm, P < 0.0001, 95% CI -1.7 to -2.9) and higher minimum vertical position of the head during stance of the outside forelimb (estimate -1.8 mm, P < 0.0001, 95% CI -1.2 to -2.5) compared to straight track, mimicking outside forelimb impact and push-off asymmetry during track curves. For hindlimb parameters, during the curve there was a decreased downward motion of the pelvis during outer hindlimb stance (estimate-0.7 mm, P < 0.0001, 95% CI -0.4 to -1.0), mimicking outside hindlimb impact asymmetry. MAIN LIMITATIONS: Horses were evaluated going in one direction only on the track (clockwise). CONCLUSIONS: Systematic differences between straight and curved track segments were found but did not fully correspond to previously described findings for horses lunged in circles. Effect sizes were overall small. Data in our study were collected from horses trotting on 1000 m tracks with curve radii of 80-85 m. On non-banked tracks of this size, collecting IMU symmetry data at jogging speeds without distinguishing between straight and curved parts is unlikely to adversely affect clinical decision-making.

Development of the blood supply to the growth cartilage of the medial femoral condyle of foals.

BACKGROUND: Growth cartilage is found in the articular-epiphyseal cartilage complex (AECC) and the physis. It has a temporary blood supply organised as end arteries. Vascular failure is associated with osteochondrosis, but infection can also obstruct vessels. The location of bacteria was recently compared to arterial perfusion, and the results indicated that they were located in the distal tips of AECC end arteries. Systematic perfusion studies were not available for comparison to the infected physes. Further studies may improve our understanding of infections and other pathologies. OBJECTIVES: To describe development of the blood supply to the growth cartilage of the medial femoral condyle in fetuses and foals from 228 days of gestation to 62 days old. STUDY DESIGN: Ex vivo arterial perfusion study. METHODS: The left medial femoral condyle of 10 Norwegian Fjord Pony fetuses and foals (228 days of gestation to 62 days old) and one Norwegian-Swedish Coldblooded Trotter foal (10 days old) was arterially perfused with barium and underwent micro-computed tomography, qualitative and quantitative description of vessels. RESULTS: In the fetus, the physis was supplied by metaphyseal-origin arteries. In 1-10 day-old foals, the physis was supplied by a mixture of metaphyseal- and epiphyseal-origin arteries, and from 15 days of age by epiphyseal-origin arteries only. The number of vessels increased before it decreased in both the AECC and the physis postnatally. Vessels in the cartilage showed a monopodial branching pattern, whereas vessels in epiphyseal and metaphyseal bone showed both monopodial and dichotomous branching. MAIN LIMITATIONS: Foals with confirmed pathologies were not examined. CONCLUSIONS: The blood supply to growth cartilage changed with age, including the physeal supply that changed from metaphyseal- to epiphyseal-origin arteries. The number of vessels increased before it decreased postnatally, and two different branching patterns were observed. These results may improve our understanding of growth cartilage vascular failure and osteomyelitis.

A bitless bridle does not limit or prevent dynamic laryngeal collapse.

BACKGROUND: Bits have often been incriminated as a cause of upper respiratory tract obstruction in horses; however, no scientific studies are available to confirm or refute these allegations. Clinical signs of dynamic laryngeal collapse associated with poll flexion (DLC) are induced when susceptible horses are ridden or driven into the bit. OBJECTIVE: To determine whether use of Dr Cook's™ Bitless Bridle, instead of a conventional snaffle bit bridle, would reduce the severity of DLC in affected horses measured objectively using inspiratory tracheal pressures. STUDY DESIGN: Intervention study using each horse as its own control in a block randomised order. METHODS: Nine Norwegian Swedish Coldblooded trotters previously diagnosed with DLC were exercised on two consecutive days using a standardised high-speed treadmill protocol with either a conventional bridle with a snaffle bit, or Dr Cook's™ Bitless Bridle. Head and neck position, rein tension, inspiratory tracheal pressure measurements, and laryngeal videoendoscopy recordings were obtained. A heart rate greater than 200 bpm, and similar degrees of poll flexion/head height, had to be achieved in both bridles for the individual horse's data to be included for comparison. RESULTS: Seven horses' data met the inclusion criteria. The change in mean inspiratory tracheal pressure between free and flexion phases in the bitless bridle (-15.2 ± 12.3 cmH2 O) was significantly greater (P < .001) than in the snaffle bit bridle (-9.8 ± 7.9 cmH2 O). Mean inspiratory pressure during the free phase was significantly (P < .001) more negative with the snaffle bit bridle (-32.3 ± 6.3 cmH2 O), vs the bitless bridle (-28.5 ± 6.9 cmH2 O). Mean pressures in flexion phase, snaffle bridle (-42.1 ± 10.8 cmH2 O), vs bitless bridle (-43.7 ± 15.6 cmH2 O) where not significantly different between bridles (P = .2). MAIN LIMITATION: Small sample size due to difficulty recruiting suitable clinical cases. CONCLUSIONS: This study could not provide any clear evidence that the effect of a snaffle bit in a horse's mouth influences the development or severity of DLC. Instead, head and neck angles induced by rein tension seem to be the key event in provoking DLC in susceptible horses.

Objectively measured movement asymmetry in yearling Standardbred trotters.

BACKGROUND: Lameness evaluation of Standardbred trotters can be challenging due to discrepancies in observed movement asymmetry between in-hand and track exercise, and between different trotting speeds. There are few studies on objective measurement of movement in Standardbreds, and little knowledge regarding biological variation and clinical significance of measured movement asymmetry in this breed. OBJECTIVES: To quantify the prevalence and magnitude of objectively measured movement asymmetry in young Standardbred trotters, and identify associations with trainer, sex, height, track type and in-hand measurement prior to or after track trials. STUDY DESIGN: Cross-sectional, observational study. METHODS: A total of 114 Standardbred yearlings were evaluated with a wireless inertial sensor system during trot in-hand and when driven on a track. After exclusions relating to lameness or technical difficulties, 103 horses were included in the study; 77 were evaluated in-hand and on the track, 24 only in-hand and 2 only on the track. RESULTS: Front and/or hindlimb parameters were above asymmetry thresholds previously established for other breeds during in-hand trials for 94 (93%) horses and during track trials for 74 (94%) horses. Most horses showed mild asymmetry. A minority of horses (20%) switched side of the asymmetry for one or more parameters between in-hand and track trials. Mixed model analyses revealed no significant effects of trial mode (in-hand or track trial, in-hand trial pre- or post-track trial, straight or oval track), trainer or horse height. Females had a significant but small reduction in asymmetry in one front limb parameter (HDmax ) compared with males (1.7 mm, 95% CI 0.18-3.28, P = .03). MAIN LIMITATIONS: High data variability, reflected in large trial standard deviations, relating mainly to a lack of horse compliance. CONCLUSIONS: A high proportion of Standardbred yearlings showed movement asymmetries. There was no group-level effect between in-hand and track trials, however, considerable individual variation was observed.

Is clinical effect of autologous conditioned serum in spontaneously occurring equine articular lameness related to ACS cytokine profile?

BACKGROUND: Biologic' therapies, such as autologous conditioned serum (ACS), are gaining popularity in treating orthopaedic conditions in equine veterinary medicine. Evidence is scarce regarding ACS constituents, and large inter-individual differences in cytokine and growth factor content have been demonstrated. The objective of the current study was to investigate the potential association between cytokine and growth factor content of ACS and clinical effect in harness racehorses with spontaneously occurring low-grade articular lameness. Horses received 3 intra-articular injections of ACS administered at approximately 2-week intervals. Lameness evaluation consisting of a trot-up with subsequent flexions tests was performed at inclusion and approximately 2 weeks after the last treatment (re-evaluation); horses were classified as responders when there was no detectable lameness on trot-up and a minimum of 50% reduction in flexion test scores at re-evaluation. Association between clinical outcome (responders vs. non-responders) and age, lameness grades at inclusion (both initial trot-up and after flexion tests), treatment interval, follow-up time and the ACS content of IL-1Ra, IGF-1 and TGF-ß was determined by regression modelling. RESULTS: Outcome analysis was available for 19 of 20 included horses; 11 responded to treatment whereas 8 did not. There was considerable inter-individual variability in cytokine/growth factor content of ACS, and in the majority of the horses, the level of IL-10, IL-1ß and TNF-α was below the detection limit. In the final multivariate logistic regression model, ACS content of IGF-1 and IL-1Ra was significantly associated with clinical response (P = 0.01 and P = 0.03, respectively). No association with clinical response was found for the other tested variables. CONCLUSIONS: The therapeutic benefit of ACS may be related to higher levels of IL-1Ra and IGF-1. Our study corroborates previous findings of considerable inter-individual variability of cytokine- and growth factor content in ACS.

Feasibility of kilohertz frequency alternating current neuromodulation of carotid sinus nerve activity in the pig.

Recent research supports that over-activation of the carotid body plays a key role in metabolic diseases like type 2 diabetes. Supressing carotid body signalling through carotid sinus nerve (CSN) modulation may offer a therapeutic approach for treating such diseases. Here we anatomically and histologically characterised the CSN in the farm pig as a recommended path to translational medicine. We developed an acute in vivo porcine model to assess the application of kilohertz frequency alternating current (KHFAC) to the CSN of evoked chemo-afferent CSN responses. Our results demonstrate the feasibility of this approach in an acute setting, as KHFAC modulation was able to successfully, yet variably, block evoked chemo-afferent responses. The observed variability in blocking response is believed to reflect the complex and diverse anatomy of the porcine CSN, which closely resembles human anatomy, as well as the need for optimisation of electrodes and parameters for a human-sized nerve. Overall, these results demonstrate the feasibility of neuromodulation of the CSN in an anesthetised large animal model, and represent the first steps in driving KHFAC modulation towards clinical translation. Chronic recovery disease models will be required to assess safety and efficacy of this potential therapeutic modality for application in diabetes treatment.

Alar fold resection in 25 horses: Clinical findings and effect on racing performance and airway mechanics (1998-2013).

OBJECTIVE: To report clinical findings and performance in horses in which alar fold collapse (AFC) had been diagnosed and surgically treated and to assess form and degree of respiratory obstruction. STUDY DESIGN: Retrospective case series. ANIMALS: Twenty-one standardbreds, 2 coldblooded trotter racehorses, 1 thoroughbred, and 1 Icelandic horse. METHODS: Alar fold collapse was diagnosed on the basis of continuous abnormal expiratory flutter noise coinciding with filling of the false nostrils during exercise on a high-speed treadmill that was alleviated by suturing the alar folds (AF) temporarily in a dorsal position. In 5 cases, nasopharyngeal airway pressures were assessed. Performance after complete, bilateral AF resection was assessed by reviewing career race records and by owner or trainer telephone interviews. RESULTS: Horses presented because of poor performance, abnormal respiratory noise, or both. Additional dynamic disorders were identified in 12 of 21 standardbreds (intermittent dorsal displacement of the soft palate: n = 10; collapse of the roof of the nasopharynx: n = 2). Expiratory nasopharyngeal pressures seemed elevated in horses with AFC (range, +10.8 to +21.8 cm H2 O) compared with normal reference values. Dorsal fixation as well as complete surgical resection of the AF improved expiratory nasopharyngeal pressures to reported normal levels. At a mean of 68 months (range, 7-121) follow-up, 20 of 25 horses had competed after surgery, and 13 of 17 of the harness racehorses had established or improved their kilometer racing time marks. CONCLUSION: Alar fold collapse caused mild to moderate expiratory obstruction and may have contributed to secondary nasopharyngeal collapse in this population. CLINICAL SIGNIFICANCE: Complete surgical resection seems effective for treating AFC. Nasopharyngeal pressure measurement is a potential tool for confirming the diagnosis of AFC.

Electrode fabrication and interface optimization for imaging of evoked peripheral nervous system activity with electrical impedance tomography (EIT).

OBJECTIVE: Non-invasive imaging techniques are undoubtedly the ideal methods for continuous monitoring of neural activity. One such method, fast neural electrical impedance tomography (EIT) has been developed over the past decade in order to image neural action potentials with non-penetrating electrode arrays. APPROACH: The goal of this study is two-fold. First, we present a detailed fabrication method for silicone-based multiple electrode arrays which can be used for epicortical or neural cuff applications. Secondly, we optimize electrode material coatings in order to achieve the best accuracy in EIT reconstructions. MAIN RESULTS: The testing of nanostructured electrode interface materials consisting of platinum, iridium oxide, and PEDOT:pTS in saline tank experiments demonstrated that the PEDOT:pTS coating used in this study leads to more accurate reconstruction dimensions along with reduced phase separation between recording channels. The PEDOT:pTS electrodes were then used in vivo to successfully image and localize the evoked activity of the recurrent laryngeal fascicle from within the cervical vagus nerve. SIGNIFICANCE: These results alongside the simple fabrication method presented here position EIT as an effective method to image neural activity.

Effect of topical vapocoolant spray on response to arthrocentesis and intravenous catheterization in unsedated horses.

OBJECTIVE: To assess the efficacy of a commercially available topical vapocoolant spray in reducing responses to arthrocentesis of the middle carpal (MC) and metacarpophalangeal (MCP) joints and jugular vein catheterization in unsedated horses. ANIMALS: 8 healthy research horses. PROCEDURES: Arthrocentesis of both MC and MCP joints and bilateral jugular vein catheterization were performed in each horse. Immediately prior to skin penetration, 1 randomly selected MC joint, MCP joint, and jugular vein were sprayed with a vapocoolant liquid (intervention product), and the contralateral MC joint, MCP joint, and jugular vein were sprayed with water (placebo). An observer blinded to the type of spray treatment used evaluated the horses' responses to needle or catheter placement procedures by use of a 6-point categorical scale and a 100-mm visual analog scale. RESULTS: Responses evaluated via the visual analog scale were significantly reduced after application of the intervention product, compared with responses after application of the placebo, for the MC and MCP joints; no difference in responses to jugular vein catheterization was detected between the 2 treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Vapocoolant spray was safe and effective in reducing horses' responses to arthrocentesis. The use of such products prior to joint injections may reduce procedural nociception and pain anticipation in unsedated horses and may improve the safety of personnel performing such procedures.

Surgical and conservative management of bilateral dynamic laryngeal collapse associated with poll flexion in harness race horses.

OBJECTIVE: To test the hypothesis that in bilateral dynamic laryngeal collapse associated with poll flexion, vocal fold collapse (VFC) is the initial abnormal event that induces further laryngeal collapse, and that racing performance would therefore be substantially improved after bilateral ventriculocordectomy in affected individuals. STUDY DESIGN: Retrospective study. ANIMALS: Twenty-six horses. METHODS: Medical records (1998-2006) of harness racehorses admitted for high-speed treadmill videoendoscopy (HSTV) that had bilateral dynamic laryngeal collapse associated with poll flexion were reviewed. Race records, owner interviews, and follow-up HSTV were used to evaluate outcome after either surgical treatment including bilateral ventriculocordectomy or conservative management. RESULTS: Bilateral dynamic laryngeal collapse, defined as bilateral VFC with concurrent arytenoid cartilage collapse (ACC), was identified in 26 horses. Norwegian Coldblooded Trotters (NCT) were overrepresented. Sixteen horses had surgical treatment and 10 were treated conservatively. Return to racing and racing performance was not improved within or between groups after the treatment. On follow-up HSTV of 6 surgically treated horses, there was no residual soft tissue collapse in the ventral portion of the rima glottidis; however, ACC and other abnormalities were still evident. CONCLUSION: Bilateral ventriculocordectomy resolved VFC, but failed to stabilize the arytenoid cartilages or to significantly improve racing performance. CLINICAL RELEVANCE: Bilateral dynamic laryngeal collapse associated with poll flexion is a serious performance-limiting upper respiratory tract disorder that is overrepresented in NCT racehorses. Our results suggest that VFC is not the initiating event in this complex obstructive airway disorder for which there is currently no consistently effective treatment.