EFFECTS OF U-74389G, A NOVEL 21-AMINOSTEROID, ON SMALL-INTESTINAL ISCHEMIA AND REPERFUSION INJURY IN HORSES

Objective--To determine the effects of the 21-aminosteroid, U-74389G, on reperfusion of the equine jejunum, using total (TVO) and partial (P VO) vascular occlusion during the ischemic period. Design-TVO: 16 heal thy horses were randomly allotted to 3 groups-4 horses received the ve hicle alone, 6 horses received a low dosage (3 mg/kg of body weight), and 6 horses a high dosage (10 mg/kg) of U-74389G. PVO: 10 healthy hor ses were randomly allotted to 2 groups-5 horses received the vehicle a lone, and 5 horses received the low dosage (3 mg/kg) of U-74389G. Proc edure-TVO was induced for 1 hour followed by 2 hours of reperfusion. D uring PVO, blood flow was reduced to 20% of baseline for 2 hours, foll owed by 2 hours of reperfusion. For both models, either the vehicle al one or the drug was given 15 minutes prior to reperfusion. Samples wer e obtained before, during, and after ischemia for determination of mye loperoxidase (MPO) activity, malondealdehyde (MDA) concentration, conc entration of conjugated dienes (PVO experiment only), and morphometric analysis. Results-TVO: tissue concentration of MDA and MPO activity w ere not altered in any group by ischemia or reperfusion. During ischem ia, mucosal volume and surface area were reduced. After reperfusion, n o further reduction occurred. After initial decrease in submucosal vol ume during ischemia, there was a significant increase after reperfusio n in the vehicle-only group (P < 0.05). PVO: there were no alterations in the concentration of either MDA or conjugated dienes. There was a significant increase in the activity of MPO during ischemia and reperf usion (P < 0.05). These effects were similar for the vehicle-only and drug groups. During ischemia, there was a significant decrease in muco sal surface area and volume (P < 0.05), that was continued during repe rfusion for the vehicle-only group (P < 0.05). Submucosal volume incre ased during reperfusion (P < 0.05). Serosal volume was increased durin g ischemia and reperfusion. Conclusions and Clinical Relevance-Reduced blood flow during ischemia (PVO group) caused continued loss in mucos al volume and surface area during reperfusion. At the dosage given, th e 21-aminosteroid, U-74389G, was not effective in preventing continued reduction in mucosal volume and surface area after restoration of blo od supply in the horses subjected to reduced blood flow.