One of the most interesting observations and one of the simplest in vitro experiments that indicates these opposite effects of sterols and fatty acids is their influence upon the oxidation processes in which red cells intervene. When a sample of ordinary venous blood is treated with a preparation of cholesterol or nonsaponifiable fractions, using the above mentioned technique and after its separation from the cholesterol it is agitated with air or oxygen which is passed through these samples, the color becomes a bright vermilion red, and this persists for a long time. When the same venous blood is treated with a preparation of polyunsaturated fatty acids as mentioned above, the color becomes very dark, almost black purple. When air or oxygen is passed through these samples, the blood becomes lighter in color for only a short time, the darker color reappearing within a few minutes. One is immediately impressed by the similarity of the cholesterol treated blood to arterial blood, while the fatty acid treated blood is similar to venous blood, and especially to the color of venous blood in cases of shock.

We tried to tie in these findings with the observation of Binet concerning the changes in blood fatty acids when passing through the lungs. He has been able to show that the amount of the polyunsaturated members appears to be reduced by the passage of blood through the lungs. We could show that the red cells leaving the pulmonary vascular bed are somewhat richer in the unbound cholesterol than they have been in the blood which entered the lungs. The lipid content is altered in an opposite way as the blood travels through the general circulation. That is, the polyunsaturated fatty acid content is increased in the red cells while the quantity of free cholesterol seems to be diminished. The sterol richer red cells appear capable of retaining for a longer period of time, the amount of oxygen which hemoglobin has fixed, while a rapid reduction of oxyhemoglobin is seen in the red cells when the polyunsaturated fatty acids intervene. This led us to consider an intervention of these two groups of lipids in relation to the oxygen transportation by the red cells. Bearing in mind the fact that while cholesterol reduces cell permeability and polyunsaturated fatty acids increase it, an alternating intervention of these lipids seems to play a role in a better distribution of oxygen. The oxygen which is fixed by hemoglobin when the red cells have passed the lungs, is largely retained as such by the intervention of the sterols until they reach the point in the tissues where liberation of oxygen is necessary, this being favored now by the intervention of the fatty acids.

Lipids And State Of Shock

The abnormally dark color of the blood resulting from its treatment in vitro with polyunsaturated fatty acids has suggested the intervention of such substances in those clinical conditions in which similar color changes are noted in the blood as in shock. We will present our studies in shock below. For the moment we will only note that in the state of shock experimentally induced by trauma, burns or irradiation, or found in terminally ill adrenalectomized animals, these animals have not only a high fatty acid content, but that the kind of fatty acids encountered are not the same as in normal animals. We have discussed these abnormal fatty acids above. The existing differences have been shown by measuring the quantity of oxalic acid that is produced when these fatty acids are submitted to a careful standardized oxidative fission. The oxidative fission of the fatty acids not only from their entire body but even from their blood has shown that for normal animals, no oxalic acid could be found, leading to the assumption that no conjugated fatty acids are present. On the other hand, oxalic acid appeared when fatty acids obtained from animals in shock or from their blood were broken down with the analytical method utilized.

Of particular significance for the pathogenic role of these fatty acids is the fact which we will discuss again below, that death appears to ensue when the conjugation of fatty acids reaches a certain value, which is approximately the same whether the animal has been traumatized, burned, irradiated or adrenalectomized, and independent of the fact that death occurs in a short time or several days. It corresponds to 14-17 mgm. of oxalic acid per gram of fatty acids. It is also interesting to note that these abnormal fatty acids were found to be more abundant in the red cells than in the plasma.

Effect Upon Leucocytes

The biological antagonism between sterols and fatty acids has appeared in the influence upon other blood constituents. We have observed that the administration of sterols tends to elevate the total white blood cell count and especially the number of neutrophilic granulocytes. Polyunsaturated fatty acids, on the other hand, produce rapid leucopenia, and again it is the neutrophile elements that are first affected. A hyperleucocytosis often was seen following the neutropenia induced by polyunsaturated fatty acids if small amounts are administered. This effect could be considered as being reactional to the first leucopenia, since it is retarded or even prevented if large doses of these fatty acids are injected. (Table XXXIII) It is also interesting to note that a deviation to the right, in Arneth's formula, was seen after the treatment with fatty acids; and to the left after treatment with sterols. Thus, this concords well with the antagonistic effects upon the aging process seen for these lipids and which is discussed below.