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Abstract

Objective—To determine the in vitro effect of prostaglandin (PG) E2, PGF, and the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin, ketoprofen, and nabumetone on the contractile strength of the circular smooth muscle layer of the third compartment of the stomach of llamas.

Sample Population—Specimens of the third compartment obtained from 5 healthy adult llamas.

Procedure—Full-thickness tissue samples were collected from the third compartment immediately after euthanasia. Specimens were cut into strips oriented along the circular muscle layer and mounted in a tissue bath system. Incremental amounts of ketoprofen, nabumetone, indomethacin, PGE2, and PGF were added, and contractile strength (amplitude of contractions) was recorded.

Results—Generally, PGE2 reduced contractile strength of the circular smooth layer of the third compartment, whereas PGF increased the strength of contractions. The activity of the NSAIDs was generally excitatory in a concentration-dependent manner, although significant changes were induced only by administration of indomethacin.

Conclusions and Clinical Relevance—On isolated smooth muscle strips of the third compartment of llamas, exogenous PGE2 and PGF had a variable effect on contractile strength. Administration of the NSAIDs did not inhibit contractility and would not be likely to induce stasis of the third compartment in the absence of an underlying disease process. (Am J Vet Res 2004;65:220–224

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in American Journal of Veterinary Research

Abstract

Objectives—To determine the in vitro effect of prostaglandin E2 (PGE2), PGF, PGI2; and nonsteroidal anti-inflammatory drugs (NSAID; ie, flunixin meglumine, ketoprofen, carprofen, and phenylbutazone) on contractile activity of the equine dorsal colon, ventral colon, and pelvic flexure circular and longitudinal smooth muscle.

Animals—26 healthy horses.

Procedure—Tissue collected from the ventral colon, dorsal colon, and pelvic flexure was cut into strips and mounted in a tissue bath system where contractile strength was determined. Incremental doses of PGE2, PGF, PGI2, flunixin meglumine, carprofen, ketoprofen, and phenylbutazone were added to the baths, and the contractile activity was recorded for each location and orientation of smooth muscle.

Results—In substance P-stimulated tissues, PGE2 and PGF enhanced contractility in the longitudinal smooth muscle with a decrease or no effect on circular smooth muscle activity. Prostaglandin I2 inhibited the circular smooth muscle response with no effect on the longitudinal muscle. The activity of NSAID was predominantly inhibitory regardless of location or muscle orientation.

Conclusions and Clinical Relevance—In the equine large intestine, exogenous prostaglandins had a variable effect on contractile activity, depending on the location in the colon and orientation of the smooth muscle. The administration of NSAID inhibited contractility, with flunixin meglumine generally inducing the most profound inhibition relative to the other NSAID evaluated in substance P-stimulated smooth muscle of the large intestine. The results of this study indicate that prolonged use of NSAID may potentially predispose horses to develop gastrointestinal tract stasis and subsequent impaction. (Am J Vet Res 2000;61:1259–1266)

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate the effect of 2 cyclooxygenase (COX)-2 inhibitors on contractile activity of the circular smooth muscle layer of the equine dorsal and ventral colon.

Sample Population—Samples of the dorsal and ventral colon obtained from 10 healthy horses.

Procedure—Full-thickness tissue samples were collected from the dorsal colon in the area of the diaphragmatic flexure and the ventral colon in the area of the sternal flexure. Samples were cut into strips oriented along the fibers of the circular muscle layer and mounted in a tissue bath system for determination of contractile strength. Incremental amounts of etodolac, nabumetone, and indomethacin were added, and contractile activity was recorded.

Results—Response of the dorsal and ventral colon to nonsteroidal anti-inflammatory drugs (NSAIDs) was variable. Indomethacin induced the greatest reduction in contractile activity, followed by nabumetone. For etodolac, the difference from baseline values was only significantly reduced at the highest concentration used (1 × 10–5M) for the ventral colon.

Conclusions and Clinical Relevance—The NSAIDs that are designed to target the COX-2 isoform appeared to have variable effects on the contractile activity of the equine dorsal and ventral colon. Etodolac appeared to have the least effect on contractile activity, compared with the effects attributable to nabumetone, and would potentially have the fewest adverse effects relative to motility of the dorsal and ventral colon. (Am J Vet Res 2002;63:1496–1500)

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in American Journal of Veterinary Research

Abstract

Objective—To characterize the texture, mineralogic features, and chemical features of enteroliths obtained from horses.

Sample Population—Enteroliths from 13 horses with colic.

Procedure—Enteroliths were harvested from 13 horses that underwent ventral midline celiotomy for treatment of colic or necropsy because of colonic obstruction and rupture caused by enteroliths. Dietary and environmental history were determined via questionnaires or evaluation of medical records. In 7 horses that underwent surgical treatment for enterolithiasis, samples of colonic contents were obtained via an enterotomy in the pelvic flexure. Colonic concentrations of magnesium (Mg), phosphorus (P), sulfur (S), sodium (Na), calcium (Ca), and potassium (K) were determined. Enteroliths were analyzed via electron microprobe analysis and X-ray diffraction.

Results—Enteroliths varied widely regarding degree of porosity, presence and distribution of radiating texture, and composition and size of the central nidus. A distinct concentric banding was identifiable in all enteroliths. Struvite was the predominant component of all enteroliths, although Mg vivianite was identified in 5 enteroliths, and there were variable quantities of Na, S, K, and Ca in the struvite within enteroliths. Despite an abundance of Ca in colonic fluids, Mgphosphate minerals were preferentially formed, compared with Ca-phosphates (apatite), in equine enteroliths.

Conclusions and Clinical Relevance—Enteroliths comprise 2 major Mg phosphates: struvite and Mg vivianite. There is wide variability in macrotexture and ionic concentrations between and within enteroliths. (Am J Vet Res 2001;62:350–358)

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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)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the role of nitric oxide and an apamin-sensitive nonadrenergic noncholingeric inhibitory transmitter on contractility of the ventral colon of horses.

Sample population—Strips of the circular and longitudinal muscle layers and taenia of the ventral colon from 14 horses.

Procedure—Muscle strips were suspended in tissue baths and attached to force transducers. Contractile activity of circular, longitudinal, and taenia muscle strips in response to electrical field stimulation was measured after addition of apamin and a nitric oxide inhibitor, N-nitro-L-arginine methyl ester (L-NAME).

Results—Electrical field stimulation reduced contractile activity in the circular muscle layer and taenia but not the longitudinal muscle layer. Addition of L-NAME significantly reduced inhibitory contractile activity at all frequencies for the circular muscle layer, whereas a significant effect was evident for the taenia only at the highest frequency. The combination of L-NAME and apamin resulted in a significant reduction in inhibition of the taenia at all frequencies but for circular muscle only at lower frequencies.

Conclusions and Clinical Relevance—Nitric oxide and an apamin-sensitive neurotransmitter appear to mediate a component of inhibitory transmission in the circular muscle and taenia, but not the longitudinal muscle layer, of the equine ventral colon. Nitric oxide has a role in regulating contractile activity of the equine ventral colon, and nitric oxide synthase inhibitors may be useful in horses with ileus of the large colon. (Am J Vet Res 2000;61:64–68)

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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)

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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)

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate electrical activity of jejunal circular muscle in horses and characterize electrical responses to stimulation by intrinsic inhibitory neurons.

Sample Population—Portions of jejunum obtained from horses euthanatized for reasons other than gastrointestinal tract disease.

Procedure—Isolated circular muscle preparations were perfused with oxygenated modified Krebs solution. Glass microelectrodes were used for intracellular recording of membrane potentials from single smooth muscle cells. Electrical activity and responses to electrical field stimulation (EFS) of intrinsic neurons in the presence of guanethidine and atropine were recorded. Mediators of responses to nerve stimulation were also evaluated, using N-nitro-L-arginine methyl ester (L-NAME) and apamin.

Results—Mean resting membrane potential (RMP) was 41.5 ± 1.8 mV. Small membrane potential oscillations were observed in muscle cells. Single or multiple action potentials were often superimposed on the peaks of these oscillations. Spontaneous oscillations and action potentials were blocked by nifedipine. Transient hyperpolarizations of smooth muscle cell membrane potentials (inhibitory junction potentials [IJP]) were observed in response to electrical field stimulation. The IJP evoked by stimulus trains consisted of an initial fast component followed by a slow component. The L-NAME did not have a significant effect on RMP and did not significantly affect the fast component of IJP at any stimulus frequency tested. In contrast, L-NAME abolished the slow component of IJP observed after trains of pulses. In the continued presence of L-NAME, apamin had no significant effect on RMP but effectively reduced the fast component of IJP.

Conclusions and Clinical Relevance—Findings suggest that inhibitory neurotransmitters supplying equine jejunum act through different ionic mechanisms. Understanding these mechanisms may suggest new therapeutic targets for treatment of motility disorders. (Am J Vet Res 2000;61:362–368)

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in American Journal of Veterinary Research

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)

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in American Journal of Veterinary Research