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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 develop a protocol to induce and maintain gastric ulceration in horses and to determine whether gastric ulceration affects physiologic indices of performance during high-speed treadmill exercise.

Animals—20 healthy Thoroughbreds.

Procedures—Each horse was acclimatized to treadmill exercise during a 2-week period. Subsequently, baseline data were collected (day 0) and each horse began an incrementally increasing exercise training program (days 1 through 56). Beginning on day 14, horses were administered omeprazole (4 mg/kg, PO, q 24 h until day 56) or no drug (10 horses/group) and underwent alternating 24-hour periods of feeding and feed withholding for 10 days to induce gastric ulceration. Extent of gastric ulceration was assessed weekly thereafter via gastroscopy. Physiologic indices of performance were measured at days 0 and 56. Gastric ulceration and exercise performance indices were compared within and between groups.

Results—In untreated horses, gastric ulcers were induced and maintained through day 56. Gastric ulcer formation was prevented in omeprazole-treated horses. There were significant interactions between time (pre- and post-training data) and treatment (nonulcer and ulcer groups) for mass-specific maximal O2 consumption ( O 2max/Mb) and mass-specific maximal CO2 production ( CO 2max/Mb). Post hoc analysis revealed a difference between groups for O 2max/Mb at day 56. Within-group differences for O 2max/Mb and CO 2max/Mb were detected for omeprazole-treated horses, but not for the horses with ulcers.

Conclusions and Clinical Relevance—In horses, gastric ulcers were induced and maintained by use of alternating periods of feeding and feed withholding in association with treadmill exercise (simulated racetrack training). Gastric ulcers adversely affected physiologic indices of performance in horses.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To use an extracorporeal circuit to evaluate effects of intraluminal distention on the jejunum of healthy horses.

Sample Population—2 jejunal segments from each of 5 horses.

Procedure—Jejunal segments were harvested and maintained in an extracorporeal circuit. One segment was subjected to distention (intraluminal pressure, 25 cm H2O) followed by decompression, and 1 segment was maintained without distention. The influence of distention-decompression on vascular resistance was calculated. Mucosal permeability was evaluated by measuring the clearance of albumin from blood to lumen. After distention and decompression, tissue specimens were collected for histomorphologic evaluation. In addition, the contractile response of the circular smooth muscle layer was determined following incubation with 3 prokinetic agents.

Results—Intestinal vascular resistance increased during intraluminal distention and returned to baseline values after decompression. Albumin clearance rate increased after distention, compared with baseline and control values. Histologic examination of the distended segments revealed grade-1 and -2 lesions of the mucosal villus. Edema and hemorrhage were evident in the submucosa and muscular layers. Mesothelial cell loss, edema, and hemorrhage were also evident in the serosa. Mucosal surface area and villus tip height decreased and submucosal volume increased in the distended tissue. Compared with responses in control specimens, distention decreased the contractile response induced by cisapride, erythromycin, and metoclopramide.

Conclusions and Clinical Relevance—Intraluminal distention of the jejunum followed by decompression increased mucosal permeability and injury and decreased responses to prokinetic agents. Horses with intraluminal intestinal distention may have a decreased response to prokinetic agents. (Am J Vet Res 2002;63:267–275)

Full access
in American Journal of Veterinary Research

Abstract

Objective

To determine whether xanthine oxidase and dehydrogenase activities are altered during low flow ischemia and reperfusion of the small intestine of horses.

Animals

5 clinically normal horses without histories of abdominal problems.

Procedure

With the horse under general anesthesia, a laparotomy was performed and blood flow to a segment of the distal jejunum was reduced to 20% of baseline for 120 minutes and was then reperfused for 120 minutes. Biopsy specimens were obtained before, during, and after ischemia for determination of xanthine oxidase and dehydrogenase activities, and for histologic and morphometric analyses.

Results

Percentage of xanthine oxidase activity (as a percentage of xanthine oxidase and dehydrogenase activity) was not altered during ischemia and reperfusion. An inflammatory response developed and progressed during ischemia and reperfusion. Mucosal lesions increased in severity after ischemia and reperfusion. Mucosal surface area and volume decreased during ischemia and continued to decrease during reperfusion. Submucosal volume increased slightly during ischemia, and continued to increase during reperfusion.

Conclusions and Clinical Relevance

Evidence for conversion of xanthine dehydrogenase to xanthine oxidase during ischemia was not found. Factors other than production of reactive oxygen metabolites may be responsible for progressive epithelial loss, decrease in mucosal surface area and volume, and increase in submucosal volume observed in this study. Other methods of determining xanthine oxidase activity that detect the enzyme in sloughed epithelial cells should be used to better define the importance of this pathway in jejunal reperfusion injury in horses. (Am J Vet Res 1998;59:772-776)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine efficacy of an extracorporeal circuit to maintain a segment of equine large colon for 3.5 hours and to evaluate the effect of low arterial flow on histologic and metabolic variables.

Sample Population—Segments of large colon from 15 healthy adult horses.

Procedure—The pelvic flexure was surgically removed and maintained in an isolated circuit. In the control group, tissue was evaluated for 3.5 hours, whereas in the low-flow group, arterial flow was reduced to 20% of baseline for 40 minutes followed by 2 hours of reperfusion. Various metabolic and hemodynamic variables were evaluated at 30-minute intervals. Effects of nitric oxide (NO) and L-N-nitro-arginine- methyl-ester (L-NAME) on contractile activity were determined, and histomorphologic evaluation was performed at the completion of the study.

Results—Low-flow ischemia with reperfusion caused significant histomorphologic differences, compared with the control group. In the low-flow group, significant differences included reduction in PaCO2, reduction in bicarbonate concentrations, increase in PaO2, and an increase in base deficit in arterial and venous blood samples. Other significant differences included increases in PCV, protein concentration, total WBC count, and albumin clearance for the low-flow group. Differences were not detected in inhibitory activity of the low-flow group relative to the control tissue with or without addition of NO and L-NAME.

Conclusion—The extracorporeal circuit maintained a segment of equine intestine for 3.5 hours and can be used to simulate ischemic injury. The extracorporeal circuit provides the potential to investigate pharmaceutic agents that can minimize intestinal injury. (Am J Vet Res 2000;61:1042–1051)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the efficacy of a customized solution to attenuate intestinal injury following 20% low-flow ischemia and reperfusion in the jejunum of horses.

Animals—10 healthy adult horses.

Procedure—Two 30.5-cm-long segments of jejunum were exteriorized through a ventral midline incision and the mesenteric artery and vein supplying that portion of the intestine were instrumented with flow probes. Blood flow was decreased to 20% of baseline for 90 minutes followed by 90 minutes of reperfusion. In 5 horses, 60 mL of the customized solution was placed in the lumen of each segment (treatment-group horses), and 60 mL of lactated Ringer's solution was placed in the lumen of 5 additional horses (control-group horses). Biopsy specimens were obtained from 1 segment in both groups for histologic evaluation. Aliquots of luminal fluid were obtained from the other segment in both groups for determination of albumin concentrations as an index of mucosal permeability.

Results—Compared with control-group horses, treatment-group horses had a significant decrease in luminal albumin concentration following reperfusion. Although differences in mucosal grades were not significantly different between control- and treatment-group horses, treatment-group horses had significantly greater jejunal villous length and area, compared with that of control-group horses.

Conclusions and Clinical Relevance—Intraluminal administration of the customized solution in the jejunum, compared with lactated Ringer's solution, results in an improvement in histologic findings and mucosal translocation of albumin in horses with mild intestinal injury. (Am J Vet Res 2004;65:485–490)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate clinical, microbiologic, and pathologic outcomes in mice after inoculation with 4 equine-origin Corynebacterium pseudotuberculosis strains.

Animals—15 C3H/HeJ mice.

Procedures—In a preliminary study, the optimum route of inoculation was determined. In the main study, mice were allocated to 4 treatment groups (3 mice/group). One slow- or rapid-growing equine-origin C pseudotuberculosis strain was inoculated ID into the mice of each treatment group.

Results—All 4 strains had distinct tropism for the liver. Histologic lesions associated with rapid-growing strains included focally extensive unencapsulated areas of acute, massive coagulative necrosis of hepatocytes with intralesional colonies of bacteria and variable portal hepatitis characterized by accumulations of mononuclear and polymorphonuclear inflammatory cells. In contrast, the livers of mice inoculated with slow-growing strains had multiple discrete, randomly distributed foci of hepatocellular necrosis and neutrophilic hepatitis that were considerably less severe than the lesions in the mice inoculated with the rapid-growing strains. Significantly more bacterial colonies were recovered from the organs of mice inoculated with rapid-growing than with slow-growing strains of bacteria. Bacteria were isolated from the liver, spleen, lungs, and mesenteric lymph nodes of mice inoculated with rapid-growing strains and from the liver and lymph nodes of mice inoculated with slow-growing strains.

Conclusions and Clinical Relevance—Study of host-bacteria interactions in hosts that are naturally infected with C pseudotuberculosis is difficult because of underlying genetic variability among animals, expense, and requirements for multiple replicates and control animals. The C3H/HeJ mice may provide a useful means for studying virulence mechanisms of C pseudotuberculosis.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of an external nasal dilator strip on cytologic characteristics of bronchoalveolar lavage (BAL) fluid in racing Thoroughbreds.

Design—Clinical trial.

Animals—23 Thoroughbred racehorses in active training.

Procedure—Each horse raced on 2 occasions: once while wearing an external nasal dilator strip and once while not. Bronchoalveolar lavage was performed 12 to 18 hours after each race, and BAL fluid was analyzed for RBC and leukocyte counts and hemosiderin content.

Results—Mean ± SEM count of RBCs in BAL fluid when horses raced without the nasal dilator strip (84.6 ± 27.5 cells/µL) was not significantly different from count when they raced with it (41.7 ± 12.2 cells/µL). Horses were grouped as having mild or severe bleeding on the basis of RBC count in BAL fluid after horses raced without the nasal dilator strip. Mean count when horses with severe bleeding raced without the nasal dilator strip (271.0 ± 63.7 cells/µL) was significantly higher than mean count when these horses raced with the strip (93.8 ± 37.6 cells/µL). Mean count of lymphocytes in BAL fluid was significantly lower after horses raced with the external nasal dilator strip.

Conclusions and Clinical Relevance—Results suggest that use of an external nasal dilator strip in Thoroughbred racehorses may decrease pulmonary bleeding, particularly in horses with severe exerciseinduced pulmonary hemorrhage. ( J Am Vet Med Assoc 2004;224:558–561)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective

To determine the effects of the 21-amino-steroid, U-74389G, on reperfusion of the equine jejunum, using total (TVO) and partial (PVO) vascular occlusion during the ischemic period.

Design

TVO: 16 healthy horses were randomly allotted to 3 groups—4 horses received the vehicle alone, 6 horses received a low dosage (3 mg/kg of body weight), and 6 horses a high dosage (10 mg/kg) of U-74389G. PVO: 10 healthy horses were randomly allotted to 2 groups—5 horses received the vehicle alone, and 5 horses received the low dosage (3 mg/kg) of U-74389G.

Procedure

TVO was induced for 1 hour followed by 2 hours of reperfusion. During PVO, blood flow was reduced to 20% of baseline for 2 hours, followed by 2 hours of reperfusion.

For both models, either the vehicle alone or the drug was given 15 minutes prior to reperfusion. Samples were obtained before, during, and after ischemia for determination of myeloperoxidase (MPO) activity, malondealdehyde (MDA) concentration, concentration of conjugated dienes (PVO experiment only), and morphometric analysis.

Results

TVO: tissue concentration of MDA and MPO activity were not altered in any group by ischemia or reperfusion. During ischemia, mucosal volume and surface area were reduced. After reperfusion, no further reduction occurred. After initial decrease in submucosal volume during ischemia, there was a significant increase after reperfusion in the vehicle-only group (P < 0.05). PVO: there were no alterations in the concentration of either MDA or conjugated dienes. There was a significant increase in the activity of MPO during ischemia and reperfusion (P< 0.05). These effects were similar for the vehicle-only and drug groups. During ischemia, there was a significant decrease in mucosal surface area and volume (P< 0.05), that was continued during reperfusion for the vehicle-only group (P< 0.05). Submucosal volume increased during reperfusion (P< 0.05). Serosal volume was increased during ischemia and reperfusion.

Conclusions and Clinical Relevance

Reduced blood flow during ischemia (PVO group) caused continued loss in mucosal volume and surface area during reperfusion. At the dosage given, the 21-aminosteroid, U-74389G, was not effective in preventing continued reduction in mucosal volume and surface area after restoration of blood supply in the horses subjected to reduced blood flow. (Am J Vet Res 1996; 57:762–770)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To assess clinical outcomes and scintigraphic findings in horses with a bone fragility disorder (BFD) treated with zoledronate (a nitrogen-containing bisphosphonate).

Design—Prospective uncontrolled clinical trial.

Animals—10 horses with evidence of a BFD.

Procedures—Signalment, history, and geographic location of horses' home environments were recorded. Physical examinations, lameness evaluations, and nuclear scintigraphy were performed. Diagnosis of a BFD was made on the basis of results of clinical and scintigraphic examination. Each horse was treated with zoledronate (0.075 mg/kg [0.034 mg/lb, IV, once]) at the time of diagnosis. Horses were reevaluated 6 months after treatment.

Results—Affected horses were from the central and coastal regions of California and had ≥ 1 clinical sign of the disorder; these included scapular deformation (n = 2), lordosis (1), nonspecific signs of musculoskeletal pain (1), and lameness that could not be localized to a specific anatomic region (9). All horses had multiple sites of increased radiopharmaceutica uptake during initial scintigraphic evaluation of the axial skeleton and bones of 1 or both forelimbs. Six months after treatment, clinical improvement (defined as improvement in the lameness score, resolution of signs of musculoskeletal pain, or both) was detected in 9 of 10 horses; scintigraphic uptake was unchanged (n = 2) or subjectively decreased (8). No adverse effects attributed to zoledronate treatment were detected.

Conclusions and Clinical Relevance—Treatment with zoledronate appeared to be useful in improving clinical outcome and scintigraphic findings in horses with a BFD; however, future placebo-controlled studies are necessary to accurately determine efficacy and long-term safety.

Full access
in Journal of the American Veterinary Medical Association