Systemic and colonic venous plasma biochemical alterations in horses during low-flow ischemia and reperfusion of the large colon.

The purpose of this study was to determine the effects of low-flow ischemia and reperfusion (I-R) of the large colon on 16 systemic venous (SV) and colonic venous (CV) plasma biochemical variables in horses. Horses (n = 24) were randomly allocated to 3 groups: sham-operated (n = 6), 6 h ischemia (n = 9), and 3 h ischemia followed by 3 h reperfusion (n = 9). SV and CV heparinized blood was collected at 0, 1, 3, 3.25, 4, and 6 h. The SV-CV difference was calculated for each variable. The SV, CV, and SV-CV difference for albumin, total protein, and calcium decreased significantly (P < 0.05) across time in horses of all groups, but there were no differences among groups. SV phosphorous was significantly increased from baseline (BL) at 1 to 6 h in horses of all groups, but there were no differences among groups. CV phosphorous was significantly greater than BL from 1 to 6 h in group-2 horses and from 1 to 3 h in group-3 horses. SV potassium was not different among groups, but was significantly higher at 6 h, compared with BL in horses of all groups. CV potassium was significantly greater than BL from 1 to 6 h in horses of groups 2 and 3. SV glucose was greater at 6 h compared with all previous times in horses of all groups, but there were no difference among groups. CV glucose was significantly lower than BL and group-1 values in horses of groups 2 and 3 during ischemia, but returned to BL during reperfusion in group-3 horses. CV anion gap was significantly greater and SV-CV anion gap was significantly more negative in horses of groups 2 and 3, compared with group-1 horses during ischemia. The biologic relevance of these alterations is unknown, but they may contribute to histopathologic, hemodynamic, and metabolic alterations characteristic of low-flow I-R. Alternatively, these alterations may simply reflect colonic injury sustained during I-R. Results suggest that the colon utilizes glucose as a fuel and generates acid anions during low-flow ischemia. Increased CV phosphorous and potassium during I-R likely occurs as a result of leakage of intracellular stores subsequent to cellular damage.     

Equine postanaesthetic myositis: Thromboxanes,prostacyclin and prostaglandin E2 production

Arachidonic acid cyclooxygenase metabolites, thromboxane B₂ (TXB₂), prostaglandin E₂ (PGE₂) and 6-keto-prostaglandin F₁ (6-keto-PGF₁) were measured in horses where anaesthesia was maintained with halothane. Two horses suffering from postanaesthetic myositis were compared with four normal horses. TXB₂ and PGE₂ levels were higher in mixed venous blood drawn from the myopathic horses. An increase of TXB₂ and PGE₂ levels appeared when myopathic horses were rolled into dorsal recumbency after a prolonged period of lateral recumbency. One hour after the end of anaesthesia, TXB₂ had continued to increase whereas PGE₂ decreased. By measurements on blood samples drawn from the brachial vein, we have shown that the rising level of TXB₂ in mixed venous blood is mainly due to the increase of TXB₂ in blood draining the dependent leg. The origin of the rise in PGE₂ is not demonstrated in this study. 6-keto-PGF₁ did not change during anaesthesia. An explanation of this imbalance between TXB₂ and 6-keto-PGF₁ production is considered.     

Morphologic alterations observed during experimental ischemia of the equine large colon

Morphologic changes that develop sequentially in the large colon during experimentally induced ischemia were documented in 14 halothane-anesthetized horses. Colonic ischemia was induced by 4 types of vascular occlusion, 24 cm proximal and distal to the pelvic flexure. The effect of transmural (colonic wall) vascular compression combined with either venous occlusion (3 horses, group A) or venous and arterial occlusion (3 horses, group B) of the colonic vessels was studied for 1, 2, and 6 hours of occlusion. Also observed was the effect of reperfusion for 0.5 hour after release of the clamps for the 1- and 2-hour occlusions and for 1 hour after release of the clamps for the 6-hour occlusion. Effects of occluding only the colonic veins (4 horses, group C), or the colonic veins and arteries (4 horses, group D) were studied for 0.5, 1, 1.5, and 2 hours of occlusion and during reperfusion for 0.5 hour. Full-thickness intestinal biopsy specimens were obtained from the antimesenteric border of the pelvic flexure at 0, 0.25, 0.5, 0.75, 1, 1.5, and 2 hours during occlusion and at 0.5 hour after release of vascular occlusion. Biopsy specimens were obtained at hourly intervals from the 2 horses in which 6-hour occlusion was performed and at 1 hour after release of vascular occlusion. Macroscopic changes (serosal color, mucosal color, serum leakage) in the colon were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ultrastructural mucosal injury after experimental ischemia of the ascending colon in horses.

The ultrastructural injury that develops sequentially in the ascending colon during experimentally induced ischemia was examined in 6 halothane-anesthetized horses. Colonic ischemia was created by 2 types of vascular occlusion 24 cm proximal and distal to the pelvic flexure. In all horses, transmural vascular compression was created. The colonic venous circulation was obstructed in 3 horses, whereas in the other 3 horses, arterial and venous circulation was obstructed. Two additional horses were anesthetized as controls for determination of any morphologic alterations associated with the experimental protocol. Full-thickness colonic biopsy specimens were obtained from the antimesenteric border of the pelvic flexure at 0, 0.25, 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, and 5 hours during occlusion, and were studied by light and transmission electron microscopy. Morphologic alterations did not develop in the colon of control horses. Mucosal congestion was observed by light microscopy in the colon of horses with experimentally induced ischemia, but congestion developed early in those with obstructed colonic venous circulation, compared with those having arterial and venous obstruction. Inter- and intracellular vacuolation and loss of staining initially resulted in groups of 3 to 5 superficial luminal epithelial cells. Alterations in the glandular epithelium lagged behind those in the superficial epithelium, but were observed in both groups by 2 hours of obstruction. These changes progressed to 100% sloughing of all epithelium by 4.5 to 5 hours. The initial cellular alterations, which were observed by transmission electron microscopy, developed at 0.25 hour in horses with colonic venous obstruction and was characterized by inter- and intracellular edema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of phenylbutazone on the haemodynamic, acid-base and eicosanoid responses of horses to sustained submaximal exertion

The systemic haemodynamic and acid-base effects of the administration of phenylbutazone (4·4 mg kg⁻¹ intravenously) to standing and running horses were investigated. Phenylbutazone, or a placebo, was administered to each of six mares either 15 minutes before, or after 30 minutes of a 60-minute submaximal exercise test which elicited heart rates approximately 55 per cent of maximal, and to the same horses at rest. The variables examined included the cardiac output, heart rate, systemic and pulmonary arterial pressures, right atrial and right ventricular pressures, and arterial and mixed venous blood gases and pH. Serum sodium, potassium and chloride concentrations, and plasma thromboxane B₂, 6-keto-prostaglandin F_1α (6-keto-PGF_1α), and prostaglandin E₂ (PGE₂) concentrations were measured in separate studies using similar protocols in the same horses. Running produced increases in heart rate, cardiac output, mean arterial and right ventricular pressure, and decreases in total peripheral resistance. The acid:base responses to exertion were characterised by respiratory alkalosis. Exertion did not significantly influence plasma 6-keto-PGF_1α or PGE₂ concentrations but plasma thromboxane B₂ concentrations were increased significantly by 60 minutes of exertion in the untreated horses. This exercise-induced increase in plasma thromboxane B₂ concentration was inhibited by the previous administration of phenylbutazone, but phenylbutazone did not produce detectable changes in systemic haemodynamic or acid-base variables in either standing or running horses.     

Ex vivo COX-1 and COX-2 inhibition in equine blood by phenylbutazone,flunixin meglumine,meloxicam and firocoxib: Informing clinical NSAID selection

Newer cyclo-oxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs), such as firocoxib, are proposed to reduce inhibition of cyclo-oxygenase-1 (COX-1) and avoid undesirable side effects, while continuing to inhibit inflammation associated with COX-2. However, COX selectivity is typically based on in vitro testing, which may not provide sufficient information critical for treatment selection. This study investigated the pharmacokinetics and ex vivo COX-1 and COX-2 inhibition of phenylbutazone, flunixin meglumine, meloxicam and firocoxib. Horses (n = 3) were administered one of the four drugs, in a randomised cross-over design, with 3-week washout periods. For each drug, three doses were given and sampling performed. Drug plasma concentrations, thromboxane B₂ (TXB₂) and prostaglandin E₂ (PGE₂) were determined. After one dose, TXB₂ and PGE₂ levels were significantly higher in horses administered firocoxib compared to flunixin meglumine. Following the third dose, TXB₂ levels in horses administered firocoxib and meloxicam were significantly higher compared to flunixin meglumine or phenylbutazone; all drugs reduced PGE₂ to a similar degree. The mean plasma half-lives were 5.97 ± 0.47, 4.74 ± 0.14, 8.24 ± 3.74 and 47.42 ± 7.41 h for phenylbutazone, flunixin meglumine, meloxicam and firocoxib, respectively. Firocoxib and meloxicam exhibited significantly less COX-1 inhibition compared to flunixin meglumine and phenylbutazone; all drugs inhibited COX-2. The plasma half-life of firocoxib was longer than the other NSAIDs, including meloxicam. Data from this study have important clinical relevance and should be used to inform practitioners’ drug selection of a COX-1 sparing or traditional NSAID and dose selection and to provide knowledge of the duration for the four NSAIDs studied.     

Clinical and immunomodulating effects of ketamine in horses with experimental endotoxemia

Background: Ketamine has immunomodulating effects both in vitro and in vivo during experimental endotoxemia in humans, rodents, and dogs. Hypothesis: Subanesthetic doses of ketamine will attenuate the clinical and immunologic responses to experimental endotoxemia in horses. Animals: Nineteen healthy mares of various breeds. Methods: Experimental study. Horses were randomized into 2 groups: ketamine‐treated horses (KET; n = 9) and saline‐treated horses (SAL; n = 10). Both groups received 30 ng/kg of lipopolysaccharide (LPS, Escherichia coli, O55:B5) 1 hour after the start of a continuous rate infusion (CRI) of racemic ketamine (KET) or physiologic saline (SAL). Clinical and hematological responses were documented and plasma concentrations of tumor necrosis factor‐α (TNF‐α) and thromboxane B₂ (TXB₂) were quantified. Results: All horses safely completed the study. The KET group exhibited transient excitation during the ketamine loading infusion (P < .05) and 1 hour after discontinuation of administration (P < .05). Neutrophilic leukocytosis was greater in the KET group 8 and 24 hours after administration of LPS (P < .05). Minor perturbations of plasma biochemistry results were considered clinically insignificant. Plasma TNF‐α and TXB₂ production peaked 1.5 and 1 hours, respectively, after administration of LPS in both groups, but a significant difference between treatment groups was not demonstrated. Conclusions and Clinical Importance: A subanesthetic ketamine CRI is well tolerated by horses. A significant effect on the clinical or immunologic response to LPS administration, as assessed by clinical observation, hematological parameters, and TNF‐α and TXB₂ production, was not identified in healthy horses with the subanesthetic dose of racemic ketamine utilized in this study.     

Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in healthy horses

The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three‐way, randomized, crossover design. Blood was collected at predetermined times for PGE₂ and TXB₂ concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half‐life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearance (42.61 ± 11.28 mL/h/kg). Comparison of the oral formulations revealed a higher C_max, shorter T_max, and greater AUC for the paste compared to the tablet. Bioavailability was 112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE₂ was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and 46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC₅₀ of approximately 27 ng/mL and an IC₈₀ of 108 ng/ mL for COX2 inhibition. Inhibition of TXB₂ production was not detected. This study indicates a lack of bioequivalence between the oral formulations of firocoxib when administered as a single dose to healthy horses.     

Colonic Luminal Pressure in Horses With Strangulating and Nonstrangulating Obstruction of the Large Colon

Colonic luminal pressure (median, range) measured during ventral midline celiotomy in 69 horses with strangulating obstruction (SO) of the large colon (SO; ≥ 270° large colon volvulus; 27 cm H₂O: 2 to 80 cm H₂O) was greater ( P =.0023) than that measured in 37 horses with nonstrangulating obstruction (NSO) of the large colon (NSO; ≤ 180° volvulus or a nonstrangulating displacement; 18 cm H₂O; 6 to 46 cm H₂O). Sixty-five percent (45 of 69) of horses with SO and all horses with NSO survived. Survival analysis was restricted to 59 horses with large-colon SO that survived to hospital discharge or met the criteria specified for classification as nonsurvivors. Colonic luminal pressure in nonsurvivors (48.5 cm H₂O; 34 to 80 cm H₂O) was higher ( P =.0001) than that measured in survivors (18 cm H₂O; 2 to 50 cm H₂O) of SO. From response operating characteristic curves, a luminal pressure of 38 cm H₂O optimized the distribution of horses with SO into survivor and nonsurvivor groups. Sensitivity, specificity, and positive and negative predictive values for a colonic luminal pressure greater than 38 cm H₂O in predicting nonsurvival were 0.89, 0.91, 0.72 and 0.97, respectively. Measurement of colonic luminal pressure may be useful for predicting survival in horses with colonic volvulus.     

Age‐related differences in prostaglandin E2 synthesis by equine cartilage explants and synoviocytes

Briston, L., Dudhia, J., Lees, P. Age‐related differences in prostaglandin E₂ synthesis by equine cartilage explants and synoviocytes. J. vet. Pharmacol. Therap. 33 , 268–276. Time‐ and concentration‐related actions of lipopolysaccharide (LPS) on the synthesis of prostaglandin E₂ (PGE₂) were investigated in cartilage explants and synoviocytes harvested from 3 age groups of horses, all with clinically normal joint function: group A <10 years; group B 11–20 years and group C >20 years. Cartilage explants from group A horses were least and those from group C were most sensitive to LPS. Significant increases in PGE₂ concentration (P ≤ 0.01) were obtained in group C horses in response to LPS concentrations of 1.0 μg/mL (and higher) after exposure for 24, 36 and 48 h, whereas explants from group A horses failed to respond to LPS at concentrations up to 100 μg/mL after exposure times up to 48 h. In contrast, synoviocytes from group A horses were most and those from group C horses were least sensitive to LPS stimulation. Synoviocytes from group A horses responded to LPS concentrations of 1 μg/mL (and higher) with significantly increased concentrations of PGE₂ at 24 and 36 h. Significant but numerically smaller increases in PGE₂ concentration were induced by LPS in synoviocytes from groups B and C. As the effects of high PGE₂ concentrations are catabolic for cartilage, these observations suggest that both synoviocytes and chondrocytes might exert roles in the degenerative changes which occur in cartilage in horses with osteoarthritis.     

Local and remote lesions in horses subjected to small colon distension and decompression

The purpose of this study was to observe and characterize colonic and lung lesions in horses subjected to experimental distension and decompression of the small colon. Sixteen healthy adult horses were divided into 2 groups: 9 horses that were subjected to distension of the small colon by means of a latex balloon surgically implanted in the lumen and inflated to a pressure of 40 mm Hg for 4 h, and 7 horses in which the balloon was implanted but not inflated. Colonic biopsy specimens were collected before balloon implantation, at the end of the period of obstruction, and 1.5 and 12 h after decompression and were examined for hemorrhage, edema, and neutrophil infiltration; myeloperoxidase (MPO) activity and hemoglobin concentration were measured as well. At the end of the experiment, lung samples were also collected and examined for neutrophil accumulation and MPO activity. The mucosa was not affected by luminal distension; lesions were restricted to the seromuscular layer. Neutrophil accumulation and edema were observed in the samples from both groups of horses but were greater in those from the distension group, in which there was also hemorrhage, fibrin deposition, and increased MPO activity in the seromuscular layer. Similarly, there was greater accumulation of neutrophils in the lung samples from the distension group than in those from the sham-operated group, as determined by histologic evaluation and MPO assay. These findings provide new evidence of reperfusion injury and a systemic inflammatory response, followed by remote lesions, in horses with intestinal obstruction.     

Ultrasonographic visualization of colonic mesenteric vasculature as an indicator of large colon right dorsal displacement or 180�� volvulus (or both) in horses

Visualization of colonic mesenteric vasculature during transabdominal ultrasonographic examination of horses with colic can be a predictor of right dorsal displacement of the large colon or 180° large colon volvulus, or both. Medical records of 82 horses having had surgical treatment of colic and having received a transabdominal ultrasonographic examination on admission were reviewed. Colonic mesenteric vessels were sonographically identified coursing laterally on the right side of the abdomen in 24 of the 82 cases. Horses with colonic vessels identified on ultrasound were 32.5 times more likely to be diagnosed at surgery with either large colon right dorsal displacement or 180° large colon volvulus than those in which vessels were not seen (P < 0.001). Visualization of colonic mesenteric vessels on ultrasound provided a sensitivity of 67.7%, specificity of 97.9%, positive predictive value of 95.8%, and negative predictive value of 81% for large colon right dorsal displacement or 180° large colon volvulus, or both.     

The Effects of Ischemia and Reperfusion on Mucosal Respiratory Function, Adenosine Triphosphate, Electrolyte, and Water Content in the Ascending Colon of Ponies

Objective- The purpose of this study was to examine the effects of ischemia and reperfusion on the biochemical integrity of equine colonic mucosa to assess the relative roles of ischemic- and reperfusion-induced damage.
Study Design- Two hours of no-flow ischemia experimentally induced by 720° counterclockwise ascending colon volvulus followed by 2 hours reperfusion after derotation.
Animals- Ten ponies.
Methods- Ascending colon biopsies were obtained every hour for measurement of mucosal adenosine triphosphate (ATP), water, sodium, and potassium content. Additional samples were homogenized for assay of mitochondrial respiratory function.
Results- ATP content diminished 92% after ischemia and recovered to only 44% of control levels ( P <.001 versus controls) after 2 hours reperfusion. Reperfusion increased mucosal water and decreased sodium and potassium content for the duration of the experiment. Both NADH- (pyruvate) and FADH-linked (succinate) respiration decreased after ischemia and did not recover during reperfusion indicating electron transport chain dysfunction.
Conclusions- Two hours ischemia induced severe metabolic dysfunction in equine colon mucosa which persisted throughout reperfusion. Unequivocal evidence of injury specific to reperfusion was not observed in this study suggesting that much of the damage observed during reperfusion may be a continuation of injury induced during the ischemic period and not specific to reperfusion per se.
Clinical Relevance- This study suggests that greater efforts to metabolically support ischemically injured mucosa may be an important aspect of obtaining improved survival of horses affected by ascending colon volvulus (ACV).     

Effects of clopidogrel and aspirin on platelet aggregation, thromboxane production, and serotonin secretion in horses

Background: Critically ill horses are susceptible to thrombotic disease, which might be related to increased platelet reactivity and activation. Objectives: To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function. Animals: Six healthy adult horses. Methods: Horses received clopidogrel (2 mg/kg PO q24h) or ASA (5 mg/kg PO q24h) for 5 days in a prospective randomized cross‐over design. Platelet aggregation responses to adenosine diphosphate (ADP) and collagen via optical aggregometry, and platelet secretion of serotonin (5HT) and production of thromboxane B₂ (TXB₂) by ELISA were evaluated. In horses receiving clopidogrel, high‐performance liquid chromatography analysis for clopidogrel and its carboxylic‐acid metabolite SR 26334 was performed. Results: SR 26334 was identified in all clopidogrel‐treated horses, although the parent compound was not detected. Clopidogrel resulted in decreases in ADP‐induced platelet aggregation persisting for 120 hours after the final dose. ADP‐induced platelet aggregation decreased from a baseline of 70.2 ± 14.7% to a minimum of 15.9 ± 7.7% 24 hours after the final dose (P < .001). Collagen‐induced aggregation decreased from a baseline of 93 ± 9.5% to a minimum of 70.8 ± 16.9% 48 hours after the final dose (P < .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB₂ from a baseline value of 1310 ± 1045 to 128 ± 64 pg/mL within 24 hours (P < .01). Conclusions and Clinical Importance: Clopidogrel effectively decreases ADP‐induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.     

Use of an extracorporeal circuit to evaluate effects of ischemia and reperfusion of the equine large colon

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.     

Survival and Complications After Large Colon Resection and End‐to‐End Anastomosis for Strangulating Large Colon Volvulus in Seventy‐Three Horses

Objective— To report complications and survival after large colon resection and end‐to‐end anastomosis in horses with strangulating large colon volvulus. Study Design— Retrospective case series. Animals— Horses (n=73) with strangulating large colon volvulus. Methods— Records (January 1995 to December 2005) of horses that had large colon resection and anastomosis for strangulating large colon volvulus were reviewed for complications. Follow‐up data were obtained by telephone questionnaire at least 1 year postoperatively. Cox proportional hazards model was used for multivariate association with survival time. Variables included admission date, age, temperature, heart rate, packed cell volume, total plasma protein concentration, white blood cell count, breed, and sex. Significance was set at P<.05. Results— The most common postoperative complication was diarrhea. None of the 9 variables of interest were significant for survival. Short‐term survival rate (to discharge) was 74%. Overall survival rates at 1, 2, and 3 years postoperatively were 67.8%, 66.0%, and 63.5%, respectively. Four horses died of colic in the first year after surgery. All horses surviving long‐term (>1 year) returned to their intended use (37 brood mares, 2 racehorses, and 1 show horse) with no chronic problems related to the surgical procedure. Conclusion— None of the variables examined were associated with survival. Outcomes were similar to other large studies of surgical colic in the horse. Self‐limiting diarrhea is common after large colon resection and the prognosis for survival after hospital discharge is favorable. Clinical Relevance— Horses that survive the early postoperative period and are discharged after large colon resection and anastomosis have a good chance for long‐term survival with minimal negative impact on quality of life and use.     

In vitro anti‐LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses

Flunixin meglumine (FM) is a commonly used Nonsteroidal anti‐inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti‐inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)‐induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed. Ketorolac tromethamine and FM suppressed LPS‐induced Thromboxane B₂ (TXB₂) and Prostaglandin E₂ (PGE₂) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS‐induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti‐inflammatory and analgesic effects of KT is warranted.     

Prostaglandin E2 and reactive oxygen metabolite damage in the cecum in a pony model of acute colitis

The objective of this project was to determine early tissue biochemical events associated with increased colonic secretion during the acute stage of castor-oil-induced colitis by measuring cecal mucosal and submucosal malondialdehyde (MDA) and prostaglandin E₂ (PGE₂), levels in ponies. Intestinal tissue (inflamed or healthy) samples were obtained from 4 age- and sex-matched Shetland ponies. Biochemical methods were used to determine MDA and PGE₂ levels in intestinal tissue samples from inflamed and healthy equine intestine. Inflamed tissue MDA and PGE₂ levels increased with time after castor oil challenge and correlated with granulocyte infiltration, as determined by myeloperoxidase levels in a companion study. Elevated intestinal tissue MDA levels suggest that lipid peroxidation could be attributed to reactive oxygen metabolites (ROM) released from stimulated, recruited, and resident granulocytes. Tissue levels of MDA and PGE₂ suggest a role for granulocyte-derived mediators of intestinal inflammation in the massive secretory response in cases of acute equine colitis. Tissue MDA and PGE₂ levels may be useful laboratory tools to quantify and characterize intestinal secretory inflammatory responses in acute inflammatory conditions in the equine colon.     

Use of pelvic flexure biopsies to predict survival after large colon torsion in horses

OBJECTIVE: To determine if morphologic evaluation of intraoperative biopsies of the large colon could be used to accurately predict outcome in horses with large colon torsion. STUDY DESIGN: Clinical study. ANIMALS: Fifty-four horses with large colon torsion. METHODS: A full-thickness biopsy was collected from the pelvic flexure of the ascending colon after correction of naturally occurring colonic torsion. Morphologic changes were evaluated and graded for interstitial tissue to crypt ratio (I:C ratio), percentage loss of superficial and glandular epithelium, and the degree of hemorrhage and edema. These variables were then used to predict survival. RESULTS: Morphologic variables could be used to correctly predict survival or death in 51 horses (P < .0001). This corresponded to a sensitivity of 95.1% (82.2%-99.2%; 95% CI) and a specificity of 92.3% (62.0%-99.6%; 95% CI). Of 6 horses that had colonic resection, 5 survived; an accurate prediction of outcome based on morphologic criteria was made for each horse. CONCLUSIONS: Interpretation of changes in colonic morphology can be used to accurately predict postoperative survival in horses with large colon torsion. CLINICAL RELEVANCE: Use of frozen colonic tissue sections is a rapid, reliable, and relatively inexpensive method for assessing morphologic damage associated with large colon torsion during surgery. Intraoperative evaluation of pelvic flexure biopsies can aid in the prediction of survival and guide surgical judgment as to the need for colonic resection.     

Dietary risk factors and colonic pH and mineral concentrations in horses with enterolithiasis

A prospective, unmatched case control study was performed to identify dietary and environmental risk factors for enterolithiasis in horses in California and to determine whether colonic ingesta analyses differed between horses with and without enteroliths. Forty-three horses with enterolithiasis were compared with 19 horses with surgical colic attributable to nonstrangulating obstruction of the colon without enteroliths. Colonic ingesta samples were collected at surgery from horses with enteroliths and control horses. Colonic pH and colonic concentrations of magnesium, phosphorus, sulfur, sodium, calcium, potassium, and nitrogen were measured. Questionnaires were distributed to owners to determine diet and management practices. Student's t-test and Mann-Whitney tests were used to evaluate differences in pH, dry matter content, percent nitrogen, and mineral content. Associations between dietary and management risk factors and enterolith occurrence were quantified by odds ratios. Mean pH of colonic contents from horses with enterolithiasis was significantly higher than for control horses. Horses with enterolithiasis had significantly lower percent dry matter in colonic fecal samples and higher mean mineral concentrations than controls. On the basis of reported feeding and management practices, horses with enterolithiasis were fed a significantly higher proportion of alfalfa in their diet and were less likely to have daily access to pasture grass than horses without enteroliths. Results suggest that decreasing alfalfa consumption and allowing daily access to pasture grazing might reduce the risk of enterolithiasis. Dietary modifications promoting acidification of colonic contents and dilution of minerals might be beneficial as preventive measures for enterolithiasis in horses.