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Abstract

Objective—To evaluate the effects of morphine administration for 6 days on gastrointestinal tract function in healthy adult horses.

Animals—5 horses.

Procedures—Horses were randomly allocated into 2 groups in a crossover study. Horses in the treatment group received morphine sulfate at a dosage of 0.5 mg/kg, IV, every 12 hours for 6 days. Horses in the control group received saline (0.9% NaCl) solution at a dosage of 10 mL, IV, every 12 hours for 6 days. Variables assessed included defecation frequency, weight of feces produced, intestinal transit time (evaluated by use of barium-filled spheres and radiographic detection in feces), fecal moisture content, borborygmus score, and signs of CNS excitement and colic.

Results—Administration of morphine resulted in gastrointestinal tract dysfunction for 6 hours after each injection. During those 6 hours, mean ± SD defecation frequency decreased from 3.1 ± 1 bowel movements in control horses to 0.9 ± 0.5 bowel movements in treated horses, weight of feces decreased from 4.1 ± 0.7 kg to 1.1 ± 0.7 kg, fecal moisture content decreased from 76 ± 2.7% to 73.5 ± 2.9%, and borborygmus score decreased from 13.2 ± 2.9 to 6.3 ± 3.9. Mean gastrointestinal transit time was also increased, compared with transit times in control horses.

Conclusions and Clinical Relevance—Morphine administered at 0.5 mg/kg twice daily decreased propulsive motility and moisture content in the gastrointestinal tract lumen. These effects may predispose treated horses to development of ileus and constipation.

Full access
in American Journal of Veterinary Research

Abstract

Objective

To determine the role of nitric oxide and an apamin-sensitive nonadrenergic-noncholinergic inhibitory transmitter in in vitro contractile activity of the third compartment in llamas.

Sample Population

Isolated strips of third compartment of the stomach from 5 llamas.

Procedure

Strips were mounted in tissue baths containing oxygenated Kreb's buffer solution and connected to a polygraph chart recorder to measure contractile activity. Atropine, guanethidine, and indomethacin were added to tissue baths to inhibit muscarinic receptors, adrenoreceptors, and prostaglandin synthesis. Responses to electrical field stimulation following addition of the nitric oxide antagonist Νω-nitro-L-arginine methyl ester (L-NAME) and apamin were evaluated.

Results

Electrical field stimulation (EFS) resulted in a reduction in the amplitude and frequency of contractile activity, followed by rebound contraction when EFS was stopped. Addition of L-NAME resulted in a significant reduction in inhibition of contractile activity. Addition of apamin also resulted in a significant reduction in inhibitory contractile activity at most stimulation frequencies. The combination of L-NAME and apamin resulted in a significant reduction in inhibition at all frequencies.

Conclusion

Nitric oxide and a transmitter acting via an apamin-sensitive mechanism appear to be involved in inhibition of contractile activity of the third compartment in llamas.

Clinical Relevance

Results suggest that nitric oxide plays an important role in mediating contractile activity of the third compartment in llamas. Use of nitric oxide synthase inhibitors may have a role in the therapeutic management of llamas with lesions of the third compartment. (Am J Vet Res 1998;59:1166— 1169)

Free access
in American Journal of Veterinary Research

Abstract

Objectives

To determine the in vitro effect of various prostaglandins (PG) and nonsteroidal anti-inflammatory drugs (NSAID) on contractile activity of the large-colon taenia of horses.

Animals

14 healthy horses.

Procedure

The taenia was collected from the ventral colon, cut into strips (2 × 10 mm), and mounted in a tissue bath system (20-ml capacity) that contained oxygenated Krebs buffer solution warmed to 37.5 ± 0.5 C. After equilibration, incremental doses of PGE2, PGF, PGI2, flunixin meglumine, carprofen, ketoprofen, and phenylbutazone were added to the baths, and contractile activity was recorded. Magnitude of the response was calculated by comparing contractile activity before and after administration of the PG or NSAID to the tissue baths.

Results

PGE2 and PGF caused a significant increase in contractile activity, whereas PGL2 induced an inhibitory response. Activity of NSAID on contraction was predominantly inhibitory. At low concentrations, ketoprofen induced an excitatory effect, which then became inhibitory at high concentrations. Compared with the other NSAID, carprofen significantly reduced contractile activity at lower concentrations.

Conclusions

PGE2 and PGF appear to enhance contractility of large-colon taenia of horses, whereas PGL2 was inhibitory in the in vitro model. Administration of NSAID also inhibited contractility, with carprofen having the most potent effect.

Clinical Relevance

Administration of NSAID in combination with liberation of endogenous PG may predispose horses to development of intestinal stasis and subsequent impaction. (Am J Vet Res 1999;60:1004-1009)

Free access
in American Journal of Veterinary Research

Objective

To characterize, in mares, changes in peritoneal fluid that occurred within the first 7 days after routine foaling.

Design

Prospective observational trial.

Animals

15 mares.

Procedure

Abdominocentesis was performed within 10 days before foaling and again 12 hours, 3 days, and 7 days after each horse foaled. Data recorded for each sample included total nucleated cell count, differential cell count, specific gravity, fibrinogen concentration, and total protein concentration. Smears of each sample were examined by a single clinical pathologist.

Results

There were not any significant differences over time in specific gravity, total protein concentration, fibrinogen concentration, total nucleated cell count, or number of small mononuclear cells. Mean numbers of neutrophils and large mononuclear cells in samples collected after foaling were significantly higher than mean numbers in samples collected before foaling. For 11 of 14 horses, all samples were characterized cytologically as transudates without cytologic abnormalities.

Clinical Implications

Results of analysis of peritoneal fluid from peripartum mares suggest that nucleated cell count, protein concentration, and specific gravity of peritoneal fluid from mares that have recently foaled should be normal. Thus, peritoneal fluid abnormalities detected in mares within a week after foaling should usually be attributed to a systemic or gastrointestinal problem and not to the foaling process itself. (J Am Vet Med Assoc 1996;209:1280–1282)

Free access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine effect of leukocyte depletion on hematologic, morphologic, and metabolic variables of equine jejunum after induction of arterial lowflow ischemia and reperfusion by use of an extracorporeal circuit.

Animals—14 healthy adult horses.

Procedure—A segment of jejunum was surgically removed and maintained in an isolated circuit for 3 hours (control group), arterial flow was reduced to 20% of baseline for 40 minutes followed by 1 hour of reperfusion (low-flow group), or leukocyte depletion was filter-induced, and low-flow ischemia and reperfusion were conducted as in the low-flow control group (filter-treated group). Various metabolic, hemodynamic, and histomorphologic variables were evaluated, including effects of electrical field stimulation and L- N-nitro-arginine-methyl-ester (L-NAME) on contractile activity.

Results—The extracorporeal circuit appeared to maintain the jejunum within physiologic limits for an extended period. Low-flow ischemia with reperfusion induced significant differences in various measurements, compared with control specimens. Significant differences were not detected between the low-flow and filter-treated groups. Myeloperoxidase activity was greater in the low-flow group than the control group, whereas a difference was not detected between control and filter-treated groups.

Conclusions and Clinical Relevance—The extracorporeal circuit maintained intestine for 3 hours in a physiologic state and may be used for simulation of tissue injury. Leukocyte depletion generally did not attenuate the effects of low-flow ischemia and reperfusion on equine small intestine. ( Am J Vet Res 2001;62:87–96)

Full 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 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 describe the ultrasonographic and quantitative histologic effect of injecting 2% iodine in almond oil (IAO) and ethanolamine oleate (EO) in the medial and middle patellar ligaments of horses and to determine whether a difference in response exists between IAO and EO treatment.

Animals—10 healthy horses.

Procedure—In 5 horses, the medial and middle patellar ligaments of 1 limb were injected with EO, whereas IAO was injected in the medial and middle patellar ligaments of another 5 horses. Ultrasonographic evaluation was performed on the experimental and control limb before injection of IAO and EO and prior to euthanasia to determine cross-sectional area and evaluate fiber pattern. The patellar ligaments were harvested 2 weeks after injection and examined histologically to evaluate the inflammatory response, fibroplasia, and chondroid metaplasia.

Results—Injection of the patellar ligaments with IAO resulted in a greater increase in cross-sectional area on ultrasonography than EO. Both agents caused a decrease in echogenicity of the ligament. Histologically, significantly greater infiltration of inflammatory cells and fibroplasia developed after injection with IAO, compared with EO. Both agents resulted in significantly greater fibroplasia relative to control specimens.

Conclusions and Clinical Relevance—Injection of the medial and middle patellar ligaments with IAO induces more severe inflammation and fibroplasia than EO. Maturation of the inflammatory and fibrous response may contribute to resolution or attenuation of upward fixation of the patella by subsequent stiffening of the ligaments. (Am J Vet Res 2002;63:738–743)

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 determine the pharmacokinetics and effects of the morphine antagonist N-methylnaltrexone (MNTX) on gastrointestinal tract function in horses when administered alone and in combination with morphine.

Animals—5 healthy adult horses.

Procedures—Horses were treated with MNTX (1 mg/kg, IV), and serial blood samples were collected for determination of drug pharmacokinetics. For evaluation of effects on the gastrointestinal tract when administered alone, MNTX was administered at a dosage of 0.75 mg/kg, IV, twice daily for 4 days. For evaluation of effects when administered concurrently with morphine, MNTX (0.75 mg/kg, IV, q 12 hours) and morphine (0.5 mg/kg, IV, q 12 hours) were administered for 6 days. Gastrointestinal variables evaluated were defecation frequency, weight of feces produced, fecal moisture content, intestinal transit time, and borborygmus scores.

Results—The time-concentration data for MNTX disposition best fit a 2-compartment model with a steady-state volume of distribution of 244.6 ± 21.8 mL/kg, t1/2 of 47.04 ± 11.65 minutes, and clearance of 11.43 ± 1.06 mL/min/kg. Adverse effects were not observed at doses ≤ 1 mg/kg. Administration of MNTX increased daily fecal weight. When administered concurrently with morphine, MNTX partially prevented the effects of morphine on the gastrointestinal tract by increasing defecation frequency, fecal weight, fecal moisture content, and borborygmus score, and by preventing increases in intestinal transit time.

Conclusions and Clinical Relevance—Because MNTX does not cross the blood-brain barrier, administration of the drug should not alter the analgesic effects of opioids and may attenuate the adverse gastrointestinal effects associated with use of opioids in horses.

Full access
in American Journal of Veterinary Research