Abstract
Summary
We have recently reported the isolation and identification of leucine from the plasma of shocked animals which exerted significant cardiodepressant activity in vitro. This study tested the hypothesis that if leucine is a circulating-factor in vivo and if this has any significant deleterious effects in the shocked animal, then the exogenous administration of leucine should accelerate the shock syndrome. We infused leucine, isoleucine (7.6 mmole/kg), or KH into endotoxin-shocked rats and measured survival times and blood concentrations of leucine and isoleucine. Following endotoxin administration, the leucine-administered rats died significantly sooner (P < 0.01) than the KH-infused animals; the isoleucine animals also died sooner (P = 0.06). Terminal leucine concentrations were elevated in all animals following endotoxin administration compared to preshock concentrations. The terminal serum leucine concentration in the leucine- and isoleucine-infused groups was significantly higher (P < 0.06) than the KH-infused group. In contrast, terminal serum isoleucine concentrations were significantly elevated only in the isoleucine-infused group. These data suggest that the elevated serum leucine concentration may contribute to the development of irreversible shock.
This research was supported by Grant HL 19977 from the National Institutes of Health. Dr. Goldfarb is the recipient of Career Research Development Award HL-00947. We thank Mrs. Joanne Bayreuther for her assistance in the preparation of this manuscript.
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