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Abstract

Objective—To investigate gene expression of the major proteolytic systems and growth regulators in skeletal muscle of horses with myopathy associated with pituitary pars intermedia dysfunction (PPID).

Animals—14 horses with PPID-associated myopathy and 7 healthy control horses.

Procedures—Horses with PPID and controls were age matched (15 to 28 years old). Muscle biopsy specimens were collected from both groups and processed for RNA and cDNA extraction. Validation of the most stable housekeeping genes for skeletal muscle was performed and used to compare gene expression of the following proteolytic systems: cysteine aspartate protease–dependent systems (caspases), lysosomal-dependent systems (cathepsins), non–lysosomal calcium protease–dependent systems (calpains), and ubiquitin-proteasome–dependent systems (ubiquitins). Gene expression of negative regulators of muscle growth (myostatin and inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α) was also determined.

Results—No significant difference between groups was detected in expression of the major proteolytic systems except for m-calpain, which was greater in horses with PPID. No differences in gene expression of myostatin and interleukin-1β, interleukin-6, and tumor necrosis factor-α were detected between groups.

Conclusions and Clinical Relevance—Greater expression of m-calpain may suggest that calpains play an important role in development of muscle atrophy in horses with PPID. However, because posttranslational events may alter protein activation, inactivation, and functions not studied here, other mechanisms of muscle atrophy cannot be excluded.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To compare clinical findings and short-term outcome for horses with intestinal entrapment in the gastrosplenic ligament (GLE) with those of horses with intestinal entrapment in the epiploic foramen (EFE).

DESIGN Retrospective case-control study.

ANIMALS 43 horses with GLE (cases) and 73 horses with EFE (controls).

PROCEDURES Medical records of horses examined because of colic at a veterinary teaching hospital between 1992 and 2012 were reviewed. Signalment was extracted from medical records for all horses with colic (colic population), and additional information regarding colic history, clinical findings, treatments, and outcome was extracted from the records of horses in which GLE or EFE was diagnosed during surgery or necropsy. Signalment was compared between the colic population and the case and control populations. Clinical findings and short-term outcome were compared between the cases and controls.

RESULTS The proportions of middle-aged horses and geldings in both the case and control groups were greater than those in the colic population. Mean heart rate and blood and peritoneal fluid lactate concentrations in horses with EFE were significantly greater than those for horses with GLE. The proportion of horses that underwent surgery and were discharged from the hospital (short-term survival rate) did not differ between the GLE (22/25 [88%]) and EFE (29/34 [85%]) groups.

CONCLUSIONS AND CLINICAL RELEVANCE Compared with the colic population, results suggested middle-aged geldings might be predisposed to GLE and EFE. The short-term survival rate was similar between the GLE and EFE groups even though horses with EFE had more severe systemic derangements than did horses with GLE.

Full access
in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE

To assess the diagnostic value of plasma and peritoneal fluid procalcitonin concentrations for identification of horses with strangulating intestinal lesions.

ANIMALS

65 horses with signs of colic of intestinal origin and 10 healthy (control) horses.

PROCEDURES

For each horse, plasma and peritoneal fluid samples were obtained for a CBC and determination of total protein, procalcitonin, and lactate concentrations. Signalment and clinicopathologic findings were compared among control horses and horses with strangulating and nonstrangulating intestinal lesions.

RESULTS

Mean ± SD plasma (274.9 ± 150.8 pg/mL) and peritoneal fluid (277 ± 50.6 pg/mL) procalcitonin concentrations for horses with colic were significantly greater than the mean ± SD plasma (175.5 ± 46.0 pg/mL) and peritoneal fluid (218.8 ± 48.7 pg/mL) procalcitonin concentrations for control horses. Mean procalcitonin concentration in peritoneal fluid, but not plasma, differed significantly between horses with strangulating lesions and those with nonstrangulating lesions. A peritoneal fluid procalcitonin concentration ≥ 281.7 pg/mL had a sensitivity of 81%, specificity of 69%, positive predictive value of 56.7%, and negative predictive value of 87.9% for detection of strangulating lesions.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that peritoneal fluid procalcitonin concentration, when evaluated in conjunction with other clinicopathologic results, might be a sensitive indicator of intestinal ischemia and facilitate early identification of horses that require surgery to address a strangulating lesion.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate the efficacy of intraluminal administration of a customized solution during low-flow ischemia and reperfusion in the jejunum of horses.

Sample Population—Segments of jejunum obtained from 13 healthy adult horses.

Procedure—In isolated segments of jejunum maintained in an extracorporeal circuit, arterial flow was reduced to 20% of baseline for 40 minutes (ischemia) followed by 60 minutes of reperfusion. In 2 groups, a customized solution (concentrations, 12.5 and 25%, respectively) was placed in the lumen prior to lowflow ischemia and maintained during reperfusion. The control group received intraluminal lactated Ringer's solution for the same duration. Various metabolic, hemodynamic, histologic, and permeability variables were recorded.

Results—The 12.5% solution resulted in less histomorphologic injury and reduced mucosal permeability to albumin, compared with the 25% solution and the lactated Ringer's solution. Morphologic injury and permeability were reduced in tissues that received the 25% solution, compared with the control group, but this difference was not significant.

Conclusions and Clinical Relevance—Use of a 12.5% customized solution appeared to minimize injury in the isolated extracoporeal jejunal loop, which provides some indication that it might be useful in clinical situations. (Am J Vet Res 2002;63:1389–1394)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether a customized solution could attenuate the effects of low-flow ischemia and reperfusion injury of the equine jejunum.

Sample Population—A segment of jejunum obtained from 21 healthy adult horses.

Procedure—A segment of jejunum was maintained in an isolated extracorporeal circuit, and arterial flow was reduced to 20% of baseline for 40 minutes (ischemia) followed by 60 minutes of reperfusion. In 1 group, a customized solution was infused at a rate of 1 ml/min during low-flow ischemia and 3 ml/min during reperfusion. In a second group, the solution was infused at the same rate during low-flow ischemia, but it was infused at a rate of 7 ml/min during reperfusion. Control groups received lactated Ringer's solution administered at the same rates as for the customized solution. Various metabolic, hemodynamic, histologic, and permeability variables were recorded.

Results—A lower flow rate during reperfusion (3 ml/min) had a beneficial effect, compared with lactated Ringer's solution or the higher flow rate (7 ml/min). Use of the solution at this rate resulted in less histomorphologic injury and reduced mucosal permeability to albumin.

Conclusions and Clinical Relevance—Use of a customized solution at a lower flow rate during repurfusion appeared to have a protective effect on equine jejunum when administered IV during low-flow ischemia and reperfusion. (Am J Vet Res 2001; 62:1679–1686)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine effects of cisapride and 5-hydroxytryptamine (5-HT) on the jejunum of horses.

Sample Population—Jejunal muscle strips from 8 horses.

Procedure—Muscle strips were suspended in isolated muscle baths. Isometric stress responses to 5-HT and cisapride, with and without specific antagonists, were determined.

Results—Muscle strips incubated with atropine and tetrodotoxin responded to 5-HT and cisapride with an increase in contractile force. The 5-HT caused a concentration-dependent increase in contractile amplitude, with a maximum response (Emax) of 1,151 ± 214 g/cm2 and a molar concentration that induces contractile force equal to 50% of maximum response (EC50) of 0.028 ± 0.002 µM. Prior incubation with the 5-HT2 antagonist ketanserin decreased the Emax (626 ± 147 g/cm2) and potency (EC50, 0.307 ± 0.105 µM) of 5-HT. Prior incubation with the 5-HT3 antagonist tropisetron decreased the efficacy (Emax, 894 ± 184 g/cm2) to 5-HT. Cisapride also caused a concentrationdependent increase in contractile amplitude, with an Emax of 331 ± 82 g/cm2 and an EC50 of 0.302 ± 0.122 µM. Prior incubation with ketanserin decreased the Emax (55 ± 17 g/cm2) and potency (EC50, 0.520 ± 0.274 µM) of cisapride.

Conclusion and Clinical Relevance—Stimulatory effects of 5-HT and cisapride on circular smooth muscle of equine jejunum are mediated primarily through a noncholinergic effect. The effects of 5-HT are mediated, at least partially, by 5-HT2 and 5-HT3 receptors, whereas the effects of cisapride are mediated primarily by 5-HT2 receptors. This may impact treatment of horses with postoperative ileus. (Am J Vet Res 2000;61:1561–1565)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate effects of erythromycin, lidocaine, and metoclopramide on smooth muscle of the pyloric antrum (PA), proximal portion of the duodenum (PD), and middle portion of the jejunum (MJ) of horses.

Sample Population—Strips of smooth muscle from 7 horses.

Procedure—Isolated muscle strips were suspended in a bath and attached to isometric force transducers. Once stable spontaneous contractions were observed, agents were added. Isometric stress responses were compared with the amplitude of spontaneous contractions.

Results—A single dose of erythromycin to the PA increased contractile amplitude (CA) for the longitudinal smooth muscle (mean ± SEM, 76 ± 16 g/cm2) but decreased CA for circular smooth muscle (–79 ± 23 g/cm2). The inhibitory effect was decreased by tetrodotoxin, NG-nitro-L-arginine methyl ester, and a vasoactive intestinal peptide antagonist. Erythromycin increased CA for the MJ, which was maximal at 10–4 M (171 ± 36 g/cm2). Lidocaine increased CA for the PD, which was maximal at 10–4M (60 ± 5 g/cm2). Metoclopramide increased the CA, which was maximal at 10–4 M for the PA (75 ± 26 g/cm2), PD (279 ± 33 g/cm2), and MJ (456 ± 59 g/cm2).

Conclusions—Regional differences in responses to erythromycin, lidocaine, and metoclopramide were evident in the gastrointestinal tract of horses. Metoclopramide increased CA in all tissues used, whereas erythromycin inhibited CA in circular smooth muscle but stimulated CA in longitudinal smooth muscle from the PA. Inhibition is caused by stimulation of inhibitory nerves and is mediated, in part, by nitric oxide and vasoactive intestinal peptide. (Am J Vet Res 2000;61:413–419)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of domperidone on in vivo and in vitro measures of gastrointestinal tract motility and contractility in healthy horses.

Sample—18 adult horses and tissue samples from an additional 26 adult horses.

Procedures—Domperidone or placebo paste was administered to healthy horses in a 2-period crossover study. Gastric emptying was evaluated after oral administration of domperidone paste (1.1 or 5.0 mg/kg) or placebo paste by means of the acetaminophen absorption test in 12 horses. Frequency of defecation, weight of feces produced, fecal moisture, and stomach-to-anus transit time of microspheres were evaluated after administration of domperidone paste (1.1 mg/kg) or placebo paste in 6 horses. The effect of domperidone on smooth muscle contractile activity in samples of duodenum, jejunum, ileum, or colon obtained from 26 horses immediately after euthanasia (for nonsystemic medical problems) was investigated.

Results—Oral administration of 5.0 mg of domperidone/kg increased peak plasma acetaminophen concentration and area under the curve, indicating increased gastric emptying. Administration of 1.1 mg of domperidone/kg had no effect on gastric emptying, transit time, defecation frequency, or amount and moisture of excreted feces. Contractile activities of circular and longitudinal muscle strips from the duodenum, jejunum, ileum, or colon were not altered by domperidone. Dopamine increased contractile activity of longitudinal muscle strips but not that of circular muscle strips from the midjejunum. Domperidone decreased the dopamine-induced contractile activity of midjejunal longitudinal muscle strips.

Conclusions and Clinical Relevance—The potential beneficial effects of domperidone in horses with ileus need to be evaluated in horses with decreased gastric emptying or adynamic ileus.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine the median time to maximum concentration (tmax) of amikacin in the synovial fluid of the tarsocrural joint following IV regional limb perfusion (IVRLP) of the drug in a saphenous vein of horses.

ANIMALS

7 healthy adult horses.

PROCEDURES

With each horse sedated and restrained in a standing position, a 10-cm-wide Esmarch tourniquet was applied to a randomly selected hind limb 10 cm proximal to the point of the tarsus. Amikacin sulfate (2 g diluted with saline [0.9% NaCl] solution to a volume of 60 mL) was instilled in the saphenous vein over 3 minutes with a peristaltic pump. Tarsocrural synovial fluid samples were collected at 5, 10, 15, 20, 25, and 30 minutes after completion of IVRLP. The tourniquet was removed after collection of the last sample. Amikacin concentration was quantified by a fluorescence polarization immunoassay. Median maximum amikacin concentration and tmax were determined.

RESULTS

1 horse was excluded from analysis because an insufficient volume of synovial fluid for evaluation was obtained at multiple times. The median maximum synovial fluid amikacin concentration was 450.5 μg/mL (range, 304.7 to 930.7 μg/mL), and median tmax was 25 minutes (range, 20 to 30 minutes). All horses had synovial fluid amikacin concentrations ≥ 160 μg/mL (therapeutic concentration for common equine pathogens) at 20 minutes after IVRLP.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that, in healthy horses, maintaining the tourniquet for 20 minutes after IVRLP of amikacin in a saphenous vein was sufficient to achieve therapeutic concentrations of amikacin in the tarsocrural joint.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To describe the clinical and laboratory findings, diagnostic features, and outcome of tracheal collapse in American Miniature Horses at a referral institution.

Design—Retrospective case series.

Animals—13 American Miniature Horses with tracheal collapse.

Procedures—Medical records of American Miniature Horses with tracheal collapse at a referral hospital were reviewed. Data extracted included signalment, history, clinical signs, laboratory data, diagnostic procedures, outcome, and histologic findings.

Results—Tracheal collapse was documented in 5.6% of American Miniature Horses admitted to this referral hospital. Median age at onset of clinical signs was 11 years with a range of 2 to 15 years. Common complaints and clinical signs included respiratory distress, tachypnea, inspiratory honking noises, and increased abdominal expiratory effort, which were exacerbated by stressful events, pregnancy, exercise, a dusty environment, and eating. Tracheal collapse was confirmed by use of radiography, endoscopy, fluoroscopy, or postmortem examination. Dorsoventral flattening of the extra- or intrathoracic trachea, or both, was more common than lateral collapse. Tracheal chondromalacia was identified histologically in 4 cases, and mortality rate for affected horses was 10 of 13.

Conclusions and Clinical Relevance—Tracheal collapse was relatively common in this study of American Miniature Horses, and outcome was poor. The etiopathogenesis of the disease remains unknown.

Full access
in Journal of the American Veterinary Medical Association