The effect of cyanoacrylate on knot elongation in three sutures used for prosthetic laryngoplasty in the horse.

OBJECTIVE: This study investigated the elongation following cyclic loading on square knots of 5 USP multifilament long-chain ultra-high molecular weight polyethylene core (UHMWPE), 2 mm woven UHMWPE tape, and 5 USP braided polyester, with and without cyanoacrylate glue. STUDY DESIGN: Experimental study. SAMPLE POPULATION: n = 4. METHODS: Three conditions (suture without knot, suture with knot, suture with knot + cyanoacrylate) were evaluated for each suture material on a mechanical test stand by measuring the increased length of the construct after cycling from 25 to 50N for 1000 repetitions at 20 mm/second. Knot elongation was determined by subtracting the length of the control suture from the suture with knot or suture with knot + cyanoacrylate. The data were analyzed with a linear regression model with robust estimation of variance. Post-hoc analysis determined the model adjusted differences (square knot vs. cyanoacrylate) as a difference from control. t-tests were conducted to identify the significant findings. RESULTS: Total elongation of polyester (6.2-7.8 mm) was greater than multifilament UHMWPE (3.4-6.4 mm) and UHMWPE tape (2-3.7 mm) for all conditions. Polyester had the lowest knot elongation (1.6 mm) and the addition of cyanoacrylate decreased knot elongation for polyester by 1 mm. CONCLUSIONS: Polyester had the most total construct elongation followed by multifilament UHMWPE and UHMWPE tape. Polyester showed the least knot elongation and cyanoacrylate decreased this knot elongation. CLINICAL SIGNIFICANCE: Total construct and knot elongation should be considered as contributing factors to loss of arytenoid abduction following prosthetic laryngoplasty when using polyester, multifilament UHMWPE, or UHMWPE tape. Addition of cyanoacrylate to polyester knots should be explored to limit elongation.

Effect of a GLP-1 mimetic on the insulin response to oral sugar testing in horses.

BACKGROUND: Insulin dysregulation (ID) is the most important risk factor for the development of laminitis in horses and therapies to control it are needed. HYPOTHESIS/OBJECTIVES: To assess the effects of a single dose of the synthetic GLP-1 analog exenatide on postprandial insulin dynamics. We hypothesized that exenatide would improve insulin sensitivity and lower postprandial blood insulin concentrations. STUDY DESIGN: Randomized, crossover, experimental study. ANIMALS: Six horses (3 mares, 3 geldings; 2 with normal insulin regulation [NIR] and 4 with mild ID). METHODS: Horses completed both study arms: subcutaneous administration of exenatide (or no treatment) 30 min before an oral sugar test (0.15 ml/kg of Karo Syrup). Blood samples obtained over 240 min were assayed for glucose, insulin, lactate, c-peptide and total GLP-1. The area under the curve (AUC) was calculated using the trapezoidal rule. Insulin sensitivity (SI) was estimated using a mathematical model. RESULTS: Exenatide resulted in a postprandial decrease of 20% (effect size: 2673 µU·min/ml; 95% CI: 900 - 4446 µU·min/ml; P = 0.003) in AUC of plasma insulin (control; mean AUC insulin: 11,989 µU·min/ml; 95% CI: 9673 - 14,305 µU·min/ml, exenatide; mean AUC insulin: 9316 µU·min/ml; 95% CI: 7430 - 11,202 µU·min/ml). Exenatide resulted in an approximately threefold increase (effect size: 5.56 10-4· µU/ml-1·min-1; 95% CI: 0.95 - 10.1 10-4· µU/ml-1·min-1; P = 0.02) in estimated insulin sensitivity (control mean SI: 1.93 10-4· µU/ml-1·min-1; 95% CI: 0.005 - 3.86 10-4·µU/ml-1·min-1 vs. exenatide mean SI: 7.49 10-4· µU/ml-1·min-1; 95% CI: 3.46 - 11.52 10-4· µU/ml-1·min-1). CONCLUSIONS: The decrease in insulin response to carbohydrates was due to an increase in whole-body insulin sensitivity. GLP-1 agonists may have therapeutic potential for ID in horses.

Supporting Limb Laminitis.

Supporting limb laminitis (SLL) is a relatively frequent complication of painful limb conditions that alter normal weight-bearing patterns in horses. New evidence suggests that a lack of limb load cycling activity (normally associated with ambulation) interferes with normal perfusion of the lamellae in these cases, resulting in ischemia and dysfunction/death of cells critical to the mechanical function of the lamellae. Excessive weight-bearing load drives the progression to overt acute laminitis in the supporting limb. Monitoring and enhancement of limb load cycling activity are key strategies that may lead to successful prevention of SLL by ensuring adequate lamellar perfusion.

Evaluation of a prototype dynamic laryngoplasty system in vitro with an equine vacuum airflow system.

OBJECTIVE: To evaluate a prototype dynamic laryngoplasty system (DLPS) in a static airflow model. STUDY DESIGN: Experimental. SAMPLE POPULATION: Ten equine larynges. METHODS: The right arytenoid was fixed in abduction in all specimens. A left-sided laryngoplasty was performed with No. 2 Fiberwire and a FASTakII anchor. Each larynx was tested in a static airflow model. The system was adjusted to a flow rate of 55 L/s and prelaryngeal pressure of 12 mm Hg prior to testing in maximal arytenoid abduction. In phase 1, the left suture was loosened, shortened, and tested in 3-mm steps from 0 to 30 mm. In phase 2, the suture was tied with the DLPS in position at a target left-to-right quotient angle (LRQ) of 0.5. The DLPS was activated to target psi of 0, 25, and 50 for testing. Translaryngeal impedance (TLI), LRQ, cross-sectional areas (CSA), and resultant change in LRQ and CSA between, before, and during airflow testing were calculated. RESULTS: In phase 1, TLI was reduced by suture shortening up to 6 mm (P = .001) but not by additional shortening (P > .05). In phase 2, activation of the DLPS reduced the TLI from 0 psi (0.43 ± 0.08 mm Hg/L/s) to 25 psi (0.16 ± 0.04 mm Hg/L/s, P < .001), but no further reduction was detected at maximal psi (P = .10). CONCLUSION: Activation of the DLPS effectively reduced TLI. CLINICAL SIGNIFICANCE: These results justify further investigation of the DLPS to assess its clinical applicability.

Are There Shared Mechanisms in the Pathophysiology of Different Clinical Forms of Laminitis and What Are the Implications for Prevention and Treatment?

Laminitis is a consequence of primary disease processes elsewhere in the body. The key pathophysiologic events are insulin dysregulation in endocrinopathic laminitis, ischemia in supporting limb laminitis, and inflammation in sepsis-related laminitis. These apparently disparate mechanisms converge to cause lamellar attachment failure through epithelial cell adhesion loss and stretch, possibly mediated by common growth factor signaling pathways. Tissue damage through mechanical distraction, inflammation, pain, and a proliferative epithelial healing response are features of acute laminitis regardless of the cause. Preventive and treatment strategies based on knowledge of these unique and common mechanistic events are likely to improve clinical outcomes.

In vitro evaluation of the effect of a prototype dynamic laryngoplasty system on arytenoid abduction.

OBJECTIVE: To determine the effect of a prototype dynamic laryngoplasty system (DLPS) on arytenoid abduction. STUDY DESIGN: In vitro experimental. STUDY POPULATION: Ten equine larynges. METHODS: Dissected larynges were mounted, and the right arytenoid was maximally abducted for testing. A left-sided laryngoplasty (LP) was performed by using a strand of No. 2 FiberWire and a FASTakII anchor. Phase 1 involved tightening the suture, without the DLPS device in place, in 1-mm increments and acquiring a digital image of the rima glottidis at each increment. Phase 2 involved tying the suture with the DLPS in place at a left to right quotient (LRQ) of 0.7. Digital images were subsequently taken at 3 stages of DLPS activation (0, 25, and 50 or maximal psi) and analysed to calculate LRQ. RESULTS: All tests were completed for 9 larynges. In phase 1, a total shortening of 25.89 ± 1.27 mm was possible, which increased the LRQ from 0.59 ± 0.02 to 1.07 ± 0.12. In phase 2, activation of the DLPS increased the LRQ from 0.70 ± 0.05 to 0.97 ± 0.09. This change in LRQ equated to 18.7 mm of shortening on the basis of phase 1 results. The maximum psi of the DLPS achieved was 37.33 ± 5.96. CONCLUSION: The DLPS increased the degree of arytenoid abduction in vitro. This change in LRQ equated to 18.7 mm of shortening of the LP suture based on phase 1 results. CLINICAL IMPACT: These results support further evaluation of the DLPS to determine the effect of changes in DLPS on airway resistance.

In vitro comparison of 3 techniques of prosthesis attachment to the muscular process of the equine arytenoid cartilage.

OBJECTIVE: To determine the degree and ease of arytenoid abduction achieved with abaxial placement of a FASTak II suture anchor compared to 2 suture patterns with different directions of insertion-caudomedial to craniolateral and medial to lateral. STUDY DESIGN: Ex vivo experimental. STUDY POPULATION: Cadaveric larynges from 10 Standardbred racehorses. METHODS: Each larynx was sequentially instrumented with all 3 arytenoid suture attachment in random order: (1) abaxial placement of a FASTak II suture, (2) caudomedial to craniolateral suture, and (3) medial to lateral suture placement. Each construct was abducted at 5N increments from 0 to 25N and the left to right quotient angle ratio (LRQ) measured from digital pictures acquired at each sequential increment. RESULTS: Arytenoid abduction (higher LRQ) was greater with FASTak II construct than either of the suture patterns. The largest difference occurred at 5N. Approximately 50% less force was required to achieve an LRQ of 1.0 with the FASTak II anchor compared to the suture patterns. No difference was detected between the 2 suture constructs throughout the study. CONCLUSION: Use of the FASTak II suture anchor improved arytenoid abduction compared to 2 suture patterns and minimized the suture loads required to achieve maximum arytenoid abduction. CLINICAL RELEVANCE: Use of the FASTak II anchor may decrease the suture load required to achieve arytenoid abduction in clinical cases. This may reduce the load placed on the laryngoplasty, thereby, minimizing postoperative loss of abduction.

The influence of different horseshoes and ground substrates on mid-stance hoof orientation at the walk.

BACKGROUND: Horseshoes with modified contact surfaces combined with deformable ground substrates are used to change hoof orientation during mid-stance, for example, for therapeutic reasons. OBJECTIVES: To measure the effect of horseshoes and ground substrates on sagittal and transverse plane hoof orientation at mid-stance using a dorsal hoof wall mounted triaxial accelerometer. STUDY DESIGN: In vivo experiment, randomised crossover design. METHODS: Differences in sagittal and transverse plane angles between standing and mid-stance of the left front hoof of six horses walking with regular horseshoes, egg bar, toe-wide, medial-wide, lateral-wide and three-degree egg bar shoes on turf, sand and hard ground substrates were assessed with linear mixed models with horseshoe and substrate type as fixed factors (p < 0.05) for each animal. RESULTS: Hoof angles were significantly affected by horseshoe (p < 0.001), surface (p < 0.001) and the combination (p < 0.001). The sagittal plane angle increased in deformable ground substrates at walk-in mid-stance on turf [mean (±standard deviation): 2.6° (±3.8°)] and on sand [2.6° (±4.1°)] across all shoes. The greatest increase was observed with egg bar shoes [turf: 4.37° (±3.82°); sand 4.69° (±3.83°)]. There was a tendency for the hoof to sink laterally into deformable ground substrates among all shoes [turf: 1.11° (±1.49°); sand: 0.93° (±1.93°)]. Medial-wide shoes increased the lateral sinking [turf: 2.00° (±1.63°); sand: 1.79° (±1.58°)]. Lateral-wide shoes reduced the lateral sinking on turf [0.62° (±1.26°)] and induced a marginal medial sinking on sand [-0.007° (±2.03°)]. MAIN LIMITATIONS: The substrate properties were not quantitatively assessed, and observations were limited to front hooves at the walk. A larger sample size would be preferable. CONCLUSIONS: Mid-stance hoof orientation changes with specific combinations of shoes and ground substrates in the walking horse.

CONTEXTO: É especulado que ferraduras com solados diferentes combinadas com superfícies deformáveis podem mudar a orientação do casco durante a fase de apoio, por exemplo, por razões terapêuticas. OBJETIVOS: Mensurar o efeito de diferentes ferraduras e superfícies na orientação do casco nos planos sagital e transversal durante a fase de apoio usando um acelerômetro triaxial acoplado à parte dorsal do casco. DELINEAMENTO DO ESTUDO: Experimento in vivo, delineamento randomizado e cruzado. MÉTODOS: As diferenças entre os ângulos dos planos sagital e transverso nas diferentes fases de apoio do casco do membro anterior esquerdo de seis cavalos ao passo utilizando ferradura normal, oval, oval talonada, de pinça larga e com extensão medial ou lateral na grama, areia ou superfície dura foram avaliadas utilizando modelos mistos lineares com ferradura e tipo de superfície como fatores fixos (P < 0.05) para cada animal. RESULTADOS: Os ângulos do casco foram significativamente afetados pelo tipo de ferradura (P < 0.001), superfície (P < 0.001) e pela combinação de ambos (P < 0.001). O ângulo do plano sagital aumentou em superfícies deformáveis no passo na fase de apoio na grama (média (+/­SD): 2.6 (+/−3.8) graus) e na areia (2.6 (+/−4.1 graus) para todos os tipos de ferradura. O maior aumento foi observado com a ferradura oval (grama: 4.37 (+/− 3.82) graus; areia 4.69 (+/−3.83) graus). Houve uma tendência de o casco rebaixar mais lateralmente em superfícies deformáveis com todas as ferraduras (grama: 1.11 (+/−1.49) graus; areia: 0.93 (+/−1.93) graus). Ferraduras com extensão medial aumentaram o rebaixamento lateral (grama: 2.00 (+/−1.63) graus; areia: 1.79 (+/−1.58) graus). Ferraduras com extensão lateral reduziram o rebaixamento lateral na grama (0.62 (+/−1.26) graus) e induziram o rebaixamento medial na areia (−0.007 (+/−2.03) graus). PRINCIPAIS LIMITAÇÕES: As propriedades das superfícies não foram avaliadas quantitativamente, e as observações foram limitadas aos cascos dos membros anteriores e ao passo. Um número maior de animais no estudo seria desejável. CONCLUSÕES: A orientação do casco na fase de apoio muda de acordo com combinações específicas de ferradura e superfícies no cavalo ao passo.

Implementation of a prototype dynamic laryngoplasty system in standing sedated horses provided arytenoid abduction control at seven days postoperatively.

OBJECTIVE: Evaluate a prototype dynamic laryngoplasty system (DLPS) in horses; a feasibility study. ANIMALS: 7 healthy Standardbred adult horses. METHODS: This was an in vivo experimental study. Horses had a standing surgical procedure to induce complete laryngeal hemiplegia, which was subsequently treated using the dynamic laryngoplasty system (DLPS). Activation of the DLPS was achieved using an injection port exiting through the skin (n = 2) or a subcutaneous injection port (n = 5). For each horse, endoscopic examinations of the upper respiratory tract were performed preoperatively, intraoperatively, and 7 days postoperatively. Left-to-right quotient ratios calculated during inactivated and activated states were obtained from still images of the rima glottidis acquired during day 7. In 3 horses, the device was intentionally overinflated to evaluate for device failure, and postmortem examinations were performed on day 7. For the remaining 4 horses, upper respiratory tract endoscopy was repeated at 1 month postoperatively, with no subsequent postmortem exam. RESULTS: No perioperative complications occurred, and the DLPS was effectively delivered in all horses under standing sedation. The left-to-right quotient ratio at day 7 postoperatively could be altered from a resting position of 0.76 (± 0.06) to a maximum of 0.97 (± 0.06; P < .05). The degree of arytenoid abduction could not be significantly altered after 1 month of device implantation, suspected to be due to peri-implant fibrosis. No coughing nor tracheal contamination was observed at all time points or during inflation. CLINICAL RELEVANCE: The ability to alter the degree of abduction at 7 days postoperatively with the DLPS may be beneficial in selective cases.

The effect of pre-dosing with metformin on the insulin response to oral sugar in insulin-dysregulated horses.

BACKGROUND: A single dose of metformin administered 1 h prior to oral glucose challenge was previously shown to reduce insulinaemic responses in horses with experimentally-induced insulin dysregulation (ID). Targeted administration could be useful for controlling post-prandial hyperinsulinaemia in horses with naturally-occurring ID. OBJECTIVES: The objective was to compare the insulinaemic and glycaemic responses to oral sugar testing (OST) performed at different intervals after a single dose of metformin in horses with naturally-occurring ID. We hypothesised that pre-treatment with one dose of metformin would significantly decrease the insulinaemic response to OST. STUDY DESIGN: Randomised cross-over in vivo experiment. METHODS: Eight university-owned adult horses with naturally-occurring ID underwent OST 1, 2 and 6 h following a single oral dose of metformin (30 mg/kg) or 1 h after placebo (240 mL water) with a 7-day washout between treatments over a period of 3 weeks. Plasma insulin, C-peptide and glucose concentrations were measured at 0, 60 and 90 min after 0.45 mL/kg light corn syrup and the effect of treatment (and the interval since dosing) examined using a mixed effects linear regression model. RESULTS: Metformin treatment had no significant effect on plasma glucose, insulin or C-peptide concentrations at any time point compared with placebo (p > 0.05). For OST 1 h post metformin, median (IQR) plasma insulin was 91.3 (62.4-114.9) µIU/mL at 60 min versus 76.2 (59.1-134.5) for placebo (p = 0.8) and 62.7 (31.4-109.7) at 90 min versus 51.8 (29.2-126.3) for placebo (p = 0.9). MAIN LIMITATIONS: Small sample size may limit identification of more subtle decreases in insulin concentration with metformin pre-dosing. The results of this study are relevant only for one pre-treatment dose (30 mg/kg) which limits extrapolation to predictions about the effects of longer-term metformin administration on insulin and glucose dynamics in the horse. CONCLUSIONS AND CLINICAL IMPORTANCE: The results do not support the use of targeted metformin treatment to reduce post-prandial hyperinsulinaemia in horses with naturally-occurring ID.

Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing.

BACKGROUND: Supporting limb laminitis (SLL) is a complication of severe orthopedic disease in horses and is often life-limiting, yet the pathophysiology remains obscure. HYPOTHESIS/OBJECTIVES: To investigate the role of digital lamellar inflammatory signaling in the pathophysiology of SLL using a model of unilateral weight bearing, hypothesizing that there would be evidence of lamellar inflammation in limbs subjected to the model. ANIMALS: Thirteen healthy adult Standardbred horses were used for this study (11 geldings, 2 mares; mean age 6.5 ± 2.5 years; mean body weight 458.3 ± 32.8 kg). METHODS: Randomized controlled experimental study. A steel shoe with a custom insert was applied to a randomly selected front foot of 7 horses; 6 horses were unshod and served as controls. After 92 hours, all horses were humanely euthanized, and digital lamellar samples were collected. Lamellar protein and mRNA were isolated and used to perform western blot and PCR. RESULTS: Lamellar concentrations of IL-6 mRNA were higher in SL tissue than IL HIND tissue (median [25%-75%] normalized copy number 191 [111-3060] and 48 [25-74], respectively; P=.003), and lamellar concentrations of COX-2 mRNA were higher in SL tissue than CON tissue (normalized copy number 400 [168-634] and 125 [74-178], respectively; P=.007). Lamellar concentrations of IL-1B, IL-10, and COX-1 mRNA were not significantly different between groups. The concentrations of phosphorylated (activated) STAT1 and STAT3 proteins were higher in SL (0.5 [0.35-0.87] and 1.35 [1.1-1.7], respectively) compared to CON (0.24 [0.09-0.37] and 0.31 [0.16-037]) and UL HIND (0.27 [0.19-0.37] and 0.38 [0.24-0.5]); P=0.01 and P<0.001. CONCLUSIONS AND CLINICAL IMPORTANCE: Lamellar inflammatory signaling was higher in tissue from horses subjected to prolonged unilateral weight-bearing, suggesting that these pathways could be relevant to the pathophysiology of SLL.

Effect of sirolimus on insulin dynamics in horses.

BACKGROUND: Sirolimus, a mechanistic target of rapamycin inhibitor, suppresses insulin production in other species and has therapeutic potential for hyperinsulinemia in horses. HYPOTHESIS/OBJECTIVE: Determine the pharmacokinetics (PKs) of sirolimus and evaluate its effect on insulin dynamics in healthy and insulin dysregulation (ID) horses. ANIMALS: Eight Standardbred geldings. METHODS: A PK study was performed followed by a placebo-controlled, randomized, crossover study. Blood sirolimus concentrations were measured by liquid chromatography-mass-spectrometry. PK indices were estimated by fitting a 2-compartment model using nonlinear least squares regression. An oral glucose test (OGT) was conducted before and 4, 24, 72, and 144 hours after administration of sirolimus or placebo. Effects of time, treatment and animal on blood glucose and insulin concentrations were analyzed using mixed-effects linear regression. Sirolimus was then administered to 4 horses with dexamethasone-induced ID and an OGT was performed at baseline, after ID induction and after 7 days of treatment. RESULTS: Median (range) maximum sirolimus concentration was 277.0 (247.5-316.06) ng/mL at 5 (5-10) min and half-life was 3552 (3248-4767) min. Mean (range) oral bioavailability was 9.5 (6.8-12.4)%. Sirolimus had a significant effect on insulin concentration 24 hours after a single dose: median (interquartile range) insulin at 60 min (5.0 [3.7-7.0] µIU/mL) was 37 (-5 to 54)% less than placebo (8.7 [5.8-13.7] µIU/mL, P = .03); and at 120 min (10.2 [8.4-12.2] µIU/mL) was 28 (-15 to 53)% less than placebo (14.9 [8.4-24.8] µIU/mL, P = .02). There was minimal effect on glucose concentration. Insulin responses decreased toward baseline in ID horses after 7 days of treatment. CONCLUSION AND CLINICAL IMPORTANCE: Sirolimus decreased the insulinemic response to glucose and warrants further investigation.

Effect of ambulation following 18F-fluorodeoxyglucose injection on standing positron emission tomography of the healthy equine digit.

OBJECTIVE: Measure 18F-FDG uptake in digital tissues of healthy horses subjected to different ambulatory conditions between the time of injection and positron emission tomography (PET) scan acquisition. ANIMALS: 8 healthy adult horses. METHODS: Horses were walked (AMB) or tied in stalls (NONAMB) immediately after injection with ∼1.5 MBq/kg 18F-FDG until scan acquisition using a randomized crossover design. Steps were quantified using accelerometers. Standardized uptake values (SUV; mean and maximum) in digital tissues including the dorsal lamellae (proximal, middle, and distal), quarter lamellae (medial and lateral), and coronary band were analyzed using a mixed-effects linear regression model. RESULTS: Mean (95% CI) step count for AMB (569[484-653]) was higher than NONAMB (88[24-152]) P = <.001. The SUVmax (but not SUVmean) was increased in AMB compared with NONAMB in the proximal (2.74[2.52-2.98] vs 2.42[2.05-2.78]; P = .04) and middle (2.74[2.37-3.11] vs 2.36[2.05-2.68]; P = .03) dorsal lamellae but was not different in the distal lamellae or coronary band. In the medial quarter lamellae, both SUVmax (2.53[1.58-3.48] vs 2.07[0.81-3.33]; P = .01) and SUVmean (1.90[1.55-2.25] vs 1.49[0.91-2.06]; P = .007) were increased in AMB compared with NONAMB. The medial quarter lamellae also had lower SUVmax (P = .002) and SUVmean (P = .04) compared with the lateral quarter and lower SUVmax compared with the mid-dorsal lamellae (P = .01). CLINICAL RELEVANCE: Lamellar 18F-FDG uptake was affected by ambulatory activity mostly in the medial quarter; however, this effect was relatively small and unlikely to interfere with clinical detection of laminitis.

The effects of orally administered trazodone on ambulation and recumbency in healthy horses.

BACKGROUND: Trazodone, a serotonin receptor antagonist and reuptake inhibitor, might be a useful adjunctive treatment in the initial management of horses with acute laminitis if it minimizes ambulation or encourages recumbency. OBJECTIVES: (1) Evaluate the effects of PO trazodone on ambulatory activity and recumbency in healthy horses; and (2) assess the pharmacokinetics of multiple PO doses of trazodone. ANIMALS/METHODS: In a randomized cross-over design, 8 healthy horses received placebo or trazodone at 2 doses (2.5 and 7.5 mg/kg) PO q12h for 48 hours with a 14-day washout period between treatments. Forelimb step frequency was measured using a hoof-mounted accelerometer and continuous video monitoring was used to detect recumbency. Groups were compared using repeated measures analysis of variance with Tukey's post hoc test. Trazodone and m-chlorophenylpiperazine (m-CPP) plasma concentrations were determined by ultra-high performance liquid chromatography-tandem mass spectrometry and pharmacokinetics were analyzed using noncompartmental methods. RESULTS: Step frequency was lower in horses receiving 7.5 mg/kg trazodone than in the control group (mean step reduction: 44% ± 11%). Steps-area under the curve were significantly lower in the 7.5 mg/kg group (mean ± SD: 3375 ± 525 steps × hour) as compared to the 2.5 mg/kg group (mean ± SD: 5901 ± 2232; P = .02) and compared to control (mean ± SD: 6590 ± 1241; P = .001). No difference was found in the number of recumbent episodes (P = .92) or total duration of recumbency (P = .9). Trazodone and m-CPP achieved steady-state concentrations, with an accumulation ratio of 1.45 ± 0.2. CONCLUSIONS AND CLINICAL IMPORTANCE: Although it did not affect recumbency, trazodone at 7.5 mg/kg q12h decreased step frequency by approximately 44%.

Evaluation of locking compression plate fixation of the distal phalanx to the hoof wall as a potential therapy for laminitis.

BACKGROUND: Surgical stabilisation of the distal phalanx (DP) is a potential therapeutic strategy for severe acute laminitis. OBJECTIVE: To evaluate the effects of locking compression plate (LCP) fixation of the DP to the dorsal hoof wall. STUDY DESIGN: Ex vivo and in vivo experiments. METHODS: A T-shaped LCP was applied to one limb per pair in six pairs of cadaver forelimbs subjected to a combination of thermally induced lamellar failure and vertical load to simulate severe acute laminitis. Standard radiographic measurements were used to compare DP displacement. The LCP was then applied to one forefoot in 12 healthy Standardbred horses either standing (n = 6) or under general anaesthesia (n = 6). Lameness was evaluated daily, then horses were euthanised (day 8) and lamellar tissue analysed using light microscopy, histomorphometery and molecular markers of apoptosis. RESULTS: In the cadaver limb model, LCP fixation prevented the significant changes in hoof-distal phalanx distance, coronary extensor process distance and sole depth that characterised DP displacement in untreated limbs (p < 0.05). Application of the construct in vivo was well tolerated with minimal lameness (10/12 horses were sound at the trot on day 8); however, histology revealed dorsal lamellar pathology consistent with laminitis, but with extensive keratinocyte apoptosis. Adjacent to the LCP, caspase-3 positive cell counts were approximately 20-fold higher than control (p < 0.001). MAIN LIMITATIONS: Pathology was evaluated at a single time point. Microvascular perfusion was not evaluated. CONCLUSIONS: Rigid fixation of the DP to the hoof capsule was achieved with the LCP construct in a cadaver limb laminitis model. In live horses, LCP fixation caused regional lamellar pathology with extensive apoptosis, likely due to disturbed lamellar microvascular perfusion and/or mechanostasis. Understanding these mechanisms is critical for refinement of the technique in order to avoid iatrogenic lamellar damage.

Alfaxalone compared with ketamine for induction of anaesthesia in horses following xylazine and guaifenesin.

OBJECTIVE: To compare anaesthesia induced with either alfaxalone or ketamine in horses following premedication with xylazine and guaifenesin. STUDY DESIGN: Randomized blinded cross-over experimental study. ANIMALS: Six adult horses, five Standardbreds and one Thoroughbred; two mares and four geldings. METHODS: Each horse received, on separate occasions, induction of anaesthesia with either ketamine 2.2 mg kg(-1) or alfaxalone 1 mg kg(-1) . Premedication was with xylazine 0.5 mg kg(-1) and guaifenesin 35 mg kg(-1) . Incidence of tremors/shaking after induction, recovery and ataxia on recovery were scored. Time to recovery was recorded. Partial pressure of arterial blood oxygen (PaO(2) ) and carbon dioxide (PaO(2) ), arterial blood pressures, heart rate (HR) and respiratory rates were recorded before premedication and at intervals during anaesthesia. Data were analyzed using Wilcoxon matched pairs signed rank test and are expressed as median (range). RESULTS: There was no difference in the quality of recovery or in ataxia scores. Horses receiving alfaxalone exhibited a higher incidence of tremors/shaking on induction compared with those receiving ketamine (five and one of six horses respectively). Horses recovered to standing similarly [28 (24-47) minutes for alfaxalone; 22 (18-35) for ketamine] but took longer to recover adequately to return to the paddock after alfaxalone [44 (38-67) minutes] compared with ketamine [35 (30-47)]. There was no statistical difference between treatments in effect on HR, PaO(2) or PaCO(2) although for both regimens, PaO(2) decreased with respect to before premedication values. There was no difference between treatments in effect on blood pressure. CONCLUSIONS AND CLINICAL RELEVANCE: Both alfaxalone and ketamine were effective at inducing anaesthesia, although at induction there were more muscle tremors after alfaxalone. As there were no differences between treatments in relation to cardiopulmonary responses or quality of recovery, and only minor differences in recovery times, both agents appear suitable for this purpose following the premedication regimen used in this study.

Treatment of primary hyperparathyroidism in a Miniature Horse using chemical ablation of abnormal parathyroid tissue localized by 3-phase computed tomography.

A 15-year-old Miniature Horse mare with persistently increased plasma calcium (total and ionized) and serum parathyroid hormone concentrations was presented for suspected primary hyperparathyroidism. Ultrasonography of the thyroid region identified an enlarged heterogeneous mass axial to the right thyroid lobe suggestive of an enlarged parathyroid gland, which was further confirmed using sestamibi nuclear scintigraphy and 3-phase computed tomography. Percutaneous ultrasound-guided ethanol ablation of the mass, a method not previously described in the horse, was performed under general anesthesia resulting in rapid normalization of plasma ionized calcium and serum parathyroid hormone concentrations. Ablation of abnormal parathyroid gland tissue may be a suitable alternative to surgical resection in certain cases of primary hyperparathyroidism in the horse.

Continuous digital hypothermia reduces expression of keratin 17 and 1L-17A inflammatory pathway mediators in equine laminitis induced by hyperinsulinemia.

The euglycemic hyperinsulinemic clamp model (EHC) of equine endocrinopathic laminitis induces rapid loss of lamellar tissue integrity, disrupts keratinocyte functions, and induces inflammation similar to natural disease. Continuous digital hypothermia (CDH) blocks tissue damage in this experimental model, allowing identification of specific genes or molecular pathways contributing to disease initiation or early progression. Archived lamellar tissues (8 horses, 48 h EHC treatment, including CDH-treated front limbs) were used to measure relative expression levels of genes encoding keratin 17 (KRT17), a stress-induced intermediate filament protein, and genes upregulated downstream of keratin 17 and/or interleukin 17A (IL-17A), as mediators of inflammation. Compared to front or hind limbs at ambient temperature, CDH resulted in significantly lower expression of KRT17, CCL2, CxCL8, PTGS2 (encoding COX2), IL6, TNFα, S100A8 and MMP1. By immunofluorescence, COX2 was robustly expressed in lamellar keratinocytes from ambient limbs, but not in CDH-treated limbs. Genes not significantly reduced by CDH were IL17A, DEFB4B, S100A9 and MMP9. Overall, 8 of 12 genes were expressed at lower levels in the CDH-treated limb. These 8 genes are expressed by wounded or stress-activated keratinocytes in human disease or mouse models, highlighting the role of keratinocytes in equine laminitis.

Plasma amino acid concentrations during experimental hyperinsulinemia in 2 laminitis models.

BACKGROUND: Endocrinopathic laminitis develops in association with insulin dysregulation, but the role of insulin in the pathogenesis remains unclear. Hyperinsulinemia can cause hypoaminoacidemia, which is associated with integumentary lesions in other species and therefore warrants investigation as a potential mechanism in laminitis. OBJECTIVE: Evaluate plasma amino acid concentrations in the euglycemic-hyperinsulinemic clamp (EHC) and prolonged glucose infusion (PGI) laminitis models. ANIMALS: Sixteen Standardbred horses. METHODS: Prospective experimental study. Plasma amino acid concentrations were measured in samples collected every 6 hours from horses that underwent a 48-hour EHC (n = 8) or 66-hour PGI (n = 8) after a 24- or 6-hour baseline period in EHC and PGI groups, respectively. RESULTS: Fifteen of the 20 measured amino acid concentrations decreased over time in both EHC and PGI horses (P < 0.001). The median percentage change from baseline for these amino acids was: histidine (EHC: 41.5%; PGI: 43.9%), glutamine (EHC: 51.8%; PGI: 35.3%), arginine (EHC: 51.4%; PGI: 41%), glutamic acid (EHC: 52.4%; PGI: 31.7%), threonine (EHC: 62.8%; PGI: 25.2%), alanine (EHC: 48.9%; PGI: 19.5%), proline (EHC: 56.2%; PGI: 30.3%), cystine (EHC: 34.9%; PGI: 31.2%), lysine (EHC: 46.4%; PGI: 27.8%), tyrosine (EHC: 27.5%; PGI: 16.9%), methionine (EHC: 69.3%; PGI: 50.8%), valine (EHC: 50.8%; PGI: 34.4%), isoleucine (EHC: 60.8%; PGI: 38.7%), leucine (EHC: 48.2%; PGI: 36.6%), and phenylalanine (EHC: 16.6%; PGI: 12.1%). CONCLUSIONS AND CLINICAL IMPORTANCE: Hypoaminoacidemia develops in EHC and PGI laminitis models. The role of hypoaminoacidemia in the development of hyperinsulinemia-associated laminitis warrants further investigation.

Lamellar perfusion and energy metabolism in a preferential weight bearing model.

BACKGROUND: Supporting limb laminitis (SLL) is suspected to be caused by lamellar ischaemia as a consequence of increased mechanical load. OBJECTIVES: Examine the effects of prolonged preferential weight bearing (PWB) on lamellar perfusion and metabolism. STUDY DESIGN: In vivo experiment. METHODS: Microdialysis probes were inserted in the lamellar and sublamellar dermis of one forelimb in 13 Standardbred horses. In six horses, a platform shoe (contralateral forelimb) was used to induce increased load on the microdialysis-instrumented forelimb (PWB). The remaining seven horses were controls (CON). All horses were housed in stocks with limb weight distribution logged continuously for 92 hours. Microdialysate was collected and analysed every 4 hours for glucose, lactate, pyruvate, and lactate to pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar perfusion. Data were analysed using a mixed-effects linear regression model. RESULTS: Median [IQR] load on the microdialysis-instrumented limb was equivalent to 38.7% bwt. [37.3-40.3] in PWB and 27.3% bwt. [26.6-28] in CON. Limb offloading frequency increased in CON (P < .001) but not PWB (P = .2). Lamellar microdialysate glucose decreased in PWB (P < .001) and CON (P = .004), however, the rate of decrease was higher in PWB (P = .007). Lamellar L:P increased in PWB (P < .001) and peaked at 196 [79-656], whereas L:P did not change over time in CON (P = .6) and peaked at 42 [41-49]. Lamellar urea clearance decreased in PWB (P < .001) but not in CON (P = .3). Sublamellar L:P and urea clearance did not change over time in either group (P > .05). MAIN LIMITATIONS: The PWB model may not be representative of naturally occurring SLL. CONCLUSIONS: Evidence of lamellar ischaemia (increased L:P and decreased urea clearance) was detected exclusively in the lamellar dermis of PWB feet subjected to persistently increased load. Lamellar ischaemia is a consequence of increased mechanical load and likely contributes to the development of SLL.