Studies on the mechanism of shock: the effect of trauma on the toxicity of 3,5 dinitro-o-cresol and sodium fluoroacetate.

The effect of two non-fatal injuries, a 2 hr period of bilateral hind-limb ischaemia and a full-thickness scald of 20 per cent of the skin surface by water at 83° for 30 sec., on the toxicity of 3,5 dinitro--cresol and Na fluoroacetate has been examined in the rat. The LD of 3,5 dinitro--cresol and its hyperthermic effect were reduced by both injuries. The LD of Na fluoroacetate was unaffected by limb ischaemia. It was slightly reduced by scalding in male but not female rats. Both injuries, however, markedly inhibited the accumulation of citrate in the kidney of the fluoroacetate poisoned rat. These interactions are thought to be examples of sequential blocking and to provide circumstantial evidence in favour of the hypothesis that in the early part of the response to injury by rats at environmental temperatures below thermoneutral there is reduced activity of the tricarboxylic acid cycle with inhibition of the citrate synthase stage.