Objective—To examine the effects of flunixin meglumine (FM) on recovery of colonic mucosa from experimentally induced ischemia in horses.
Animals—14 research horses.
Procedures—Ischemia was induced in the colons of anesthetized horses for 2 hours. Afterward, horses received saline (0.9% NaCl) solution (12 mL, IV, q 12 h; n = 7) or FM (1.1 mg/kg, IV, q 12 h; 7) and were allowed to recover for 18 hours after termination of the ischemic event. Postoperative pain scores were recorded every 4 hours throughout the recovery period. At the end of the recovery period, horses were anesthetized, and ischemic and nonischemic segments of colonic mucosa were harvested for histologic evaluation, western blot analysis, and in vitro assessment of transepithelial electric resistance (TER) and transmucosal flux of tritium-labeled (3H-) mannitol. Horses were then euthanatized.
Results—Flunixin meglumine significantly lowered pain scores at the first postoperative recording. There were no significant differences between treatment with saline solution and FM in any of the measurements for TER, 3H-mannitol flux, histomorphometric variables, neutrophil infiltration (detected via calprotectin immunostaining), and expressions of cyclooxygenase-1 and -2. After both treatments, TER declined significantly in nonischemic tissues in vitro, whereas it increased significantly in ischemic-injured tissues.
Conclusions and Clinical Relevance—Flunixin meglumine did not affect recovery of equine colonic mucosa from ischemic injury, and continued use in horses with colonic ischemia is therefore justified.
Objective—To identify expression and localization of cyclooxygenase (COX)-1 and COX-2 in healthy and ischemic-injured left dorsal colon of horses.
Sample Population—Left dorsal colon tissue samples from 40 horses.
Procedures—Tissue samples that were used in several related studies on ischemia and reperfusion were evaluated. Samples were collected during anesthesia, before induction of ischemia, and following 1 hour of ischemia, 1 hour of ischemia and 30 minutes of reperfusion, 2 hours of ischemia, 2 hours of ischemia and 30 minutes of reperfusion, and 2 hours of ischemia and 18 hours of reperfusion. Histomorphometric analyses were performed to characterize morphological injury. Immunohistochemical analyses were performed to characterize expression and localization of COX-1 and COX-2.
Results—COX-1 and COX-2 were expressed in control tissues before ischemia was induced, predominantly in cells in the lamina propria. Ischemic injury significantly increased expression of COX-2 in epithelial cells on the colonic surface and in crypts. A similar significant increase of COX-1 expression was seen in the epithelial cells.
Conclusions and Clinical Relevance—On the basis of information on the role of COX-2, upregulation of COX-2 in surface epithelium and crypt cells following ischemic injury in equine colon may represent an early step in the repair process.
Objective—To assess the effects of ischemia and reperfusion on indicators of oxidative stress, activation of eosinophils, and apoptosis in the large colonic mucosa of horses.
Procedures—In 1 or two 20-cm-long segments of the pelvic flexure, ischemia was induced for 1 or 2 hours followed by no reperfusion or 30 minutes and 18 hours of reperfusion in anesthetized horses. Mucosal specimens were collected before (controls; n = 20 horses) and after each period of ischemia, and full-thickness tissue samples were collected after each period of reperfusion. Sections of colonic tissues were stained for histomorphometric analysis or assessment of eosinophil accumulation. Nitrotyrosine was identified immunohistochemically, and severity of apoptosis was determined via the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling method.
Results—Numbers of mucosal eosinophils were similar before induction of ischemia, after ischemia, and after ischemia-reperfusion. Eosinophil nitrotyrosine production increased significantly during ischemia and continued through 30 minutes of reperfusion; production was decreased at 18 hours of reperfusion but remained greater than that of the controls. In other leukocytes, nitrotyrosine generation peaked at 1 hour of ischemia and again at 18 hours of reperfusion. Compared with control findings, epithelial apoptosis increased gradually at 1 through 2 hours of ischemia with no further progression after reperfusion.
Conclusions and Clinical Relevance—Results suggested that resident eosinophils in the large colon of horses react to mucosal injury from ischemia and reperfusion and may undergo oxidative stress under those conditions. Epithelial apoptosis could contribute to tissue damage.
Case Description—Two geldings, aged 11 and 17 years, were examined for treatment of ureteroliths located approximately 10 cm proximal to the bladder.
Clinical Findings—Ureteral obstruction was an incidental finding in 1 horse that was referred because of urinary tract obstruction and a cystic calculus. This horse did not have clinical or laboratory evidence of renal failure, although severe hydronephrosis was evident on transabdominal ultrasonography. The second patient had a serum creatinine concentration of 6.3 mg/dL (reference range, 0.8 to 2.2 mg/dL) and mild hydronephrosis of the affected left kidney.
Treatment and Outcome—In both patients, the obstructed ureter was exteriorized through a flank incision as a standing procedure, and the calculus was crushed and removed with a uterine biopsy forceps introduced through a ureterotomy approximately 25 cm proximal to the calculus. The cystic calculus was removed through a perineal urethrostomy by lithotripsy, piecemeal extraction, and lavage. The horse without azotemia developed pyelonephritis in the affected kidney and was euthanatized because of complications of a nephrectomy 13 months later. In the horse with azotemia, the serum creatinine concentration decreased after surgery, and the horse returned to its intended use. However, it was euthanatized approximately 2 years after surgery because of progressive renal failure, and a large nephrolith was found in the previously unobstructed right kidney.
Clinical Relevance—The technique used for ureterolith removal was successful in both horses in this report, did not require sophisticated equipment, and could be effective in the early stages of ureteral obstruction as a means of restoring urine flow and renal function. The outcome in the horse with advanced unilateral renal disease without azotemia would suggest that nephrectomy should be considered as a treatment in such patients.