ROLE OF OXYGEN-DERIVED FREE-RADICALS ON RAT SPLANCHNIC EICOSANOID PRODUCTION DURING ACUTE HEMORRHAGE

The effect of superoxide dismutase (SOD) , an oxygen-derived free radical scavenger, on rat splanchnic eicosanoid synthesis was examined following hemorrhagic shock. Anesthetized male rats were hemorrhaged to 30 mm Hg for 30 minutes (Shock), killed, or treated with the shed blood (Shock plus reperfusion). The Shock plus reperfusion group was treated with saline vehicle or SOD (2500, 5000, 7500, 10,000 or 15,000 U/Kg, i.v.) 15 minutes prior to the reperfusion of the shed blood. The superior mesenteric artery was removed in continuity with the end organ intestine (SV+SI) and perfused in vitro with oxygenated Krebs-Henseleit buffer (3 ml/min at 37-degrees-C). Venous effluent was measured for basal release of 6-keto-PGF1-alpha, PGE2 and thromboxane B2 at 15, 30, 60 and 90 minutes of perfusion. The SV+SI compensated for acute shock by increased release of 6-keto-PGF1-alpha (300%) (and not PGE2 or thromboxane B2) which was abolished by reperfusion of the shed blood following shock. Prior treatment of the Shock plus reperfusion group with 7500 U/Kg or more of SOD restored the increased release of SV+SI 6-keto-PGF1-alpha found following shock alone (p<0.05). These data provided indirect evidence that ODFRs contributed to endogenous SV+SI regulation of PGI2 synthesis and release during hemorrhagic shock and reperfusion of shed blood.