Heat Death, Heat Injury, and Toxic Factor

Abstract

Comparisons are made between the heat death temps. of rats, guinea pigs, and cats. The heat death symptoms of rats are described. In a hot room kept at 45[degree]C (15% humidity), rats die in 79 [plus or minus] 7 mins. If only the hind legs of the rats are exposed to a temp. of 45[degree]C, the animals die in 154 [plus or minus] 7 mins., but in such expts. if the legs are tightly ligatured, no death occurs as a result of the burn. Guinea pigs are less sensitive to death by burns. When the legs of rats are burned, the muscles die before the nerves, and it is believed that the death of the muscles produces a toxic substance or substances (i.e., toxic factor), which causes the death of the entire animal. Water extracts of muscle cause death of rats when these extracts are injected intraperit. Extracts of various organs also cause death, but assays indicate a greater potency for muscle extracts. The toxicity of the extracts shows no obvious sp. specificity. The toxic factor is dialysable and soluble in absolute methyl or ethyl alcohol. There is evidence that it is present in the blood of heat-killed rabbits and burned dogs and that it can be obtained from such blood by dialysis. The extracts contain K, but K is not wholly responsible for the lethal effect. This is indicated by expts. in which extracts from heat-killed frog muscle as well as extracts from a wide variety of heat-killed living materials (sea anemones, worms, clams, squids, lobster and fish muscle) are tested for their effect on the protoplasm of the sea-urchin {Arbacia) egg. In every case, the extracts cause a protoplasmic clotting; that is to say they cause a surface precipitation reaction in the absence of Ca. Frequently, the extracts also cause a sharp increase in protoplasmic viscosity as measured by the centrifuge method. Often the increase in viscosity is, for a time at least, confined to the cortical region of the cell. The authors conclude that heat-killed tissues produce a thrombin-like substance which has an effect on protoplasmic clotting. Attempts to concentrate this substance from the extracts often lead to failure, for the substance on heating tends to combine with an insoluble protein phase. The thrombin-like substance(s) of the extract is soluble in absolute methyl or ethyl alcohol. K has no thrombin-like action on protoplasm, but presence of K rather than Na tends to preserve the potency of the extracts. The results are correlated with older knowledge that thrombin can cause shock when injected into rabbits or dogs and they may also offer an interpretation of Na therapy in burn shock. The fact that many types of injured tissues yield substances which show thrombin-like properties is in accord with protoplasmic theories of the senior author.