EFFECTS OF DIMETHYL-SULFOXIDE, ALLOPURINOL, 21-AMINOSTEROID U-74389G,AND MANGANESE CHLORIDE ON LOW-FLOW ISCHEMIA AND REPERFUSION OF THE LARGE COLON IN HORSES

Thirty horses were randomly assigned to 1 of 5 groups. AU horses were anesthetized and subjected to ventral midline celiotomy, then the larg e colon was exteriorized and instrumented. Colonic arterial blood flow was reduced to 20% of baseline (BL) and was maintained for 3 hours. C olonic blood flow was then restored, and the colon was reperfused for an additional 3 hours. One of 5 drug solutions was administered via th e jugular vein 30 minutes prior to colonic reperfusion: group 1, 0.9% NaCl; group 2, dimethyl sulfoxide: 1 g/kg of body weight; group 3, all opurinol: 25 mg/kg; group 4, 21-aminosteroid U-74389G: 10 mg/kg; and g roup 5, manganese chloride (MnCl2): 10 mg/kg. Hemodynamic variables we re monitored and recorded at 30-minutes intervals. Systemic arterial, systemic venous (SV), and colonic venous (CV) blood samples were colle cted for measurement of blood gas tensions, oximetry, lactate concentr ation, PCV, and plasma total protein concentration. The eicosanoids, 6 -keto prostaglandin F-1 alpha, prostaglandin E(2), and thromboxane B-2 , were measured in CV blood, and endotoxin was measured in CV and SV b lood. Full-thickness biopsy specimens were harvested from the left ven tral colon for histologic evaluation and determination of wet weight-t o-dry weight ratios (WW:DW). Data were analyzed, using two-way ANOVA f or repeated measures, and statistical significance was set at P < 0.05 . Heart rate, mean arterial pressure, and cardiac output increased wit h MnCl2 infusion; heart rate and cardiac output remained increased thr oughout the study, but mean arterial pressure returned to BL values wi thin 30 minutes after completion of MnCl2 infusion. Other drug-induced changes were not significant. There were significant increases in mea n pulmonary artery and mean right atrial pressures at 2 and 2.5 hours in horses of all groups, but other changes across time or differences among groups were not observed. Mean pulmonary artery pressure remaine d increased through 6 hours in all groups, but mean right atrial press ure had returned to BL values at 3 hours. Mean colonic arterial pressu re was significantly decreased at 30 minutes of ischemia and remained decreased through 6 hours; however, by 3.25 hours it was significantly higher than the value at 3 hours of ischemia. Colonic arterial resist ance decreased during ischemia and remained decreased throughout reper fusion in all groups; there were no differences among groups for colon ic arterial resistance. Colonic venous P-O2, oxygen content, and pH de creased, and P-CO2 and lactate concentration increased during ischemia but returned to BL values during reperfusion. Compared with BL values , colonic oxygen extraction ratio was increased from 0.5 to 3 hours. B y 15 minutes of reperfusion, colonic oxygen extraction ratio had decre ased from the BL value in all groups and either remained decreased or returned to values not different from BL through 6 hours. Colonic veno us 6-keto prostaglandin F-1 alpha and prostaglandin E(2) concentration s increased during ischemia, but returned to BL on reperfusion; there were no changes in thromboxane(2) concentration among or within groups . Endotoxin was not detected in CV or SV blood after ischemia or reper fusion. There were no differences among or within groups for these var iables. Low-flow ischemia and reperfusion (I-R) of the large colon cau sed mucosal injury, as evidenced by increases in percentage of surface mucosal disruption, percentage depth of mucosal loss, mucosal hemorrh age, mucosal edema, mucosal interstitial-to-crypt ratio, mucosal neutr ophil index, submucosal venular neutrophil numbers, and mucosal cellul ar debris index. There was a trend (P = 0.06) toward greater percentag e depth of mucosal loss at 6 hours in horses treated with dimethyl sul foxide, compared with the vehicle control solution. There were no diff erences in the remainder of the histologic variables among groups. Ful l-thickness and mucosal WW:DW increased with colonic I-R, but there we re no differences among groups. There was a trend (P = 0.09) toward ne utrophil accumulation, as measured by myeloperoxidase activity, in the lungs after colonic I-R, but there were no differences among groups. There was no change in lung WW:DW after colonic I-R. There were no ben eficial effects of drugs directed against oxygen-derived free radical- mediated damage on colonic mucosal injury associated with low-flow I-R . Deleterious drug-induced hemodynamic effects were not observed in th is study.