ABSTRACT
BACKGROUND: Hepatic failure is one of the more common complications in foals requiring blood transfusion to treat neonatal isoerythrolysis. Iron intoxication is likely the cause of hepatic injury. OBJECTIVES: To determine the effects of deferoxamine on iron elimination in normal foals. ANIMALS: Thirteen neonatal foals. METHODS: Randomized-controlled trial. At 1-3 days of age, foals received either 3 L of washed packed dam's red blood cells (RBC) or 3 L of saline IV once. Foals were treated with deferoxamine (1 g) or saline (5 mL) SC twice daily for 14 days. Foals were randomly assigned to 1 of 3 groups: RBC/deferoxamine (deferoxamine), RBC/saline (placebo), or saline/saline (control). Blood and urine samples and liver biopsy specimens were collected for measurement of hematological, biochemical, and iron metabolism variables. RESULTS: There was a significant (P<.05) increase in hematocrit, RBC count, and hemoglobin in the groups transfused with packed RBC as compared with controls at all times. Biochemical variables and liver biopsy scores were not significantly different between groups at any time. Urine iron concentrations and fractional excretion of iron were significantly higher in deferoxamine treated foals. By 14 days after transfusion, liver iron concentrations in foals treated with deferoxamine (79.9±30.9 ppm) were significantly lower than that of foals receiving placebo (145±53.0 ppm) and similar to that of controls (44.8±4.09 ppm). CONCLUSIONS AND CLINICAL IMPORTANCE: Deferoxamine enhances urinary iron elimination and decreases hepatic iron accumulation after blood transfusion in foals.
Subject(s)
Anemia, Hemolytic, Autoimmune/veterinary , Blood Transfusion/veterinary , Deferoxamine/therapeutic use , Horse Diseases/therapy , Iron/metabolism , Siderophores/therapeutic use , Anemia, Hemolytic, Autoimmune/therapy , Animals , Animals, Newborn , Female , Hemosiderosis/drug therapy , Hemosiderosis/veterinary , Horses , Iron/blood , MaleABSTRACT
BACKGROUND: We have previously shown that the non-selective cyclooxygenase (COX) inhibitor indomethacin retards recovery of intestinal barrier function in ischaemic injured porcine ileum. However, the relative role of COX-1 and COX-2 elaborated prostaglandins in this process is unclear. AIMS: To assess the role of COX-1 and COX-2 elaborated prostaglandins in the recovery of intestinal barrier function by evaluating the effects of selective COX-1 and COX-2 inhibitors on mucosal recovery and eicosanoid production. METHODS: Porcine ileal mucosa subjected to 45 minutes of ischaemia was mounted in Ussing chambers, and transepithelial electrical resistance was used as an indicator of mucosal recovery. Prostaglandins E1 and E2 (PGE) and 6-keto-PGF1alpha (the stable metabolite of prostaglandin I2 (PGI2)) were measured using ELISA. Thromboxane B2 (TXB2, the stable metabolite of TXA2) was measured as a likely indicator of COX-1 activity. RESULTS: Ischaemic injured tissues recovered to control levels of resistance within three hours whereas tissues treated with indomethacin (5x10(-6) M) failed to fully recover, associated with inhibition of eicosanoid production. Injured tissues treated with the selective COX-1 inhibitor SC-560 (5x10(-6) M) or the COX-2 inhibitor NS-398 (5x10(-6) M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1alpha compared with untreated tissues. However, SC-560 significantly inhibited TXB2 production whereas NS-398 had no effect on this eicosanoid, indicating differential actions of these inhibitors related to their COX selectivity. CONCLUSIONS: The results suggest that recovery of resistance is triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2.
