The hypothesis that the three types of shock are caused by the intervention of the same factor—abnormal fatty acids—has been further confirmed experimentally. The cellular changes that characterize superacute shock can be induced by the rapid introduction into the blood stream of even minimal amounts of fatty acids in preparations in which they are bound to plasma constituents.

Pooled heparinized plasma of mice was treated by stirring it in a nitrogen atmosphere for one hour with a preparation of conjugated trienic fatty acids. The nonbound fatty acids were separated through short centrifuga tion. The plasma was injected intravenously in mice. For control, plasma treated under the same conditions with stearic acid was used. While control animals did not show any apparent discomfort, the mice injected with the plasma treated with conjugated fatty acids died immediately, in most cases even during the injection itself. With such preparations, superacute shock was induced in what we consider a direct way, the sudden death contrasting with the cases of hemoshock where death occurs usually after an interval of a few minutes. This characteristic of direct immediate death is consistent with the pathogenic role of fatty acids in superacute shock.

The tissue changes that characterize the acute type of shock also may be induced by local administration of abnormal fatty acids with the condition that sufficient amounts are used. (Note 4) The systemic changes that typify the state of shock can also be produced by prolonged absorption of fatty acids, as when they are repeatedly introduced intraperitoneally. (Note 5)

The relationship between shock and lipids can be further seen in the antagonistic effect exercised upon shock induced with standardized trauma by two groups of lipids with positive and negative characters. We have utilized the Noble Collipp drum on a large scale to induce shock in rats. In some groups of animals shock induction was constant; in other groups under the same conditions, shock could be induced only in some animals. Nevertheless, it was still possible to recognize opposite effects induced by the administration of the two groups of lipids. In some animals even apparency little influenced by the trauma, the injection of a mixture of conjugated fatty acids immediately after trauma brought death within a short time. In no other animals, traumatized under the same conditions, have we seen death occurring within the same short interval of time. This also applies to animals injected before trauma. In these cases, the animals died even during the trauma, that is, in the drum. (Note 6)

Conversely, the administration of sterols, especially preparations of the insaponifiable fraction of human placenta, before induction of trauma prevented lethal shock almost without exception, whereas under the same conditions the same trauma produced death in a high proportion of the controls. Even when injected immediately after trauma, this sterol preparation prevented the development of lethal shock in a high proportion of cases. (Note 7)

The different forms of shock, although resulting from the same fundamental abnormal process, appear to respond differently to therapeutic agents—again because of the localization of the abnormal processes at different levels. Adrenalin and related compounds, when administered in time, are able to control superacute shock, but they are almost entirely without influence upon the other forms. While acute shock can be influenced by the administration of a large amount of sterols and butanol, super acute shock is unaffected, possibly also because of the slow absorption of the sterols. None of these agents is of significance in the treatment of the state of shock which is only mildly influenced by butanol and certain cortical hormones such as hydrocortisone, especially when introduced directly in the circulation.

In order to act upon the fatty acids and sodium which produce the abnormal water metabolism, we have utilized glycerophosphoric acid administered in large amounts parenterally. Diluted with saline, it was usually injected intravenously. The good results obtained are discussed later.

The use of heptanol and of polyunsaturated alcohols has also led to interesting results. It was however with preparations having several of these agents, working at different levels of the organization, that the best results were obtained.

The measurement of the chloride index and of the surface tension of the urine have represented valuable means to judge the changes occurring in shock, in their clinical evolution and especially in the action of the agents in relationship to the occurring recovery.

The study of shock has contributed to the knowledge of the therapeutic problems of cancer and other conditions. The cause of death, when a predominance of fatty acids occurs as a systemic manifestation, corresponds to the state of shock. The possibility of successfully influencing this form of shock would furnish a valuable tool for the treatment of all severe manifestations related to predominance of fatty acids.