KETOISOCAPROATE INFUSION IMPROVES SURVIVAL FROM EXPERIMENTAL SEPSIS BY AN ANTIOXIDANT MECHANISM

Sepsis was induced in rats by cecal ligation and puncture. A nutrient mixture was infused that also contained either (A) sodium 2-ketoisocap roate (NaKlC) or (B) NaHCO3, at 18.75 mmol kg/day. In group A, 34 of 4 3 rats (79%) survived, while only 24 of 44 rats (55%) in group B survi ved (P < 0.02). In a second experiment, cecal ligation and puncture we re performed 1 week after bilateral adrenalectomy or sham adrenalectom y. All adrenalectomized rats died within 2 days of CLP, whether cortic osterone replacement level was low, normal, or high. Four of eight sha m-adrenalectomized rats receiving NaHCO3 died, but none of seven recei ving NaKlC died. Combining both experiments by ANOVA, the effect of Kl C on survival in adrenal-intact animals is highly significant (P = 0.0 02). In NaKlC-infused rats, blood level of pyruvate was higher on day 5 (P < 0.01), and plasma as well as blood levels of oxidized glutathio ne and ratio of oxidized/reduced glutathione were significantly lower. We conclude that KlC infusion improves survival of septic rats by an antioxidant mechanism, probably involving reaction with hydrogen perox ide. (C) 1993 Wiley-Liss, Inc.