L-2-OXOTHIAZOLIDINE-4-CARBOXYLIC ACID PREVENTS ENDOTOXIN-INDUCED CARDIAC DYSFUNCTION

We tested the hypothesis that treatment with the glutathione repleting agent, L-2-oxothiazolidine-4-carboxylic acid (OTZ), could prevent end otoxin-induced ventricular dysfunction. Rabbits were treated with OTZ 2.4 g/kg (10% solution subcutaneously), or an equal volume and osmolal ity of saline, 24 h prior to, and again (intravenously) just prior to, infusion of 1 mg/kg E. coli endotoxin (or vehicle control). Ventricul ar contractility was measured in isolated hearts perfused by support r abbits. Contractility did not change in control groups (Saline/Control [n = 7] or OTZ/Control [n = 7]) over 6 h. However, Emax decreased in the Saline/Endotoxin group (-16.1 +/- 4.5% from baseline, n = 7, p < 0 .05) and this was prevented by pretreatment with OTZ in the OTZ/Endoto xin group (+6.3 +/- 4.1%, n = 7, p < 0.05 by analysis of variance). To better understand the mechanism of this effect we measured myocardial glutathione concentration and found it to be greater in OTZ/Endotoxin animals (104 +/- 4 ng/g) than in the Saline/Endotoxin animals (80 +/- 3 ng/g, p < 0.05). OTZ did not appreciably alter the endotoxin-induce d increase in serum concentration of tumor necrosis factor (TNF) or th e endotoxin-induced increase in myocardial leukocyte content. We concl ude that oxygen radicals contribute to the early decrease in left vent ricular contractility after endotoxin infusion and this decrease may b e prevented by OTZ.