We could find thus that organs of old animals, perfused with saline to wash them from their blood, are richer in fatty acids and poorer in sterols than those of young individuals. The cellular lipidic abnormality, corresponding to aged persons, would correspond to a quantitative predominance of fatty acids. Their analysis showed that these fatty acids correspond qualitatively to those normally encountered in the organisms and especially to the polyunsaturated members. It should be noted at this time that this predominance differs from that found in abnormal conditions which corresponds to offbalance D. In this latter case, the fatty acids are abnormal.

With the concept that cholesterol belongs to the cellular level, we studied as we did for potassium (See Chapter 5 Note 2), the concomitant changes in the amount of free cholesterol in plasma and in red cells. This was carried out to obtain information concerning the relationship between cholesterol and abnormal conditions. While a high or low amount in both plasmatic and cellular cholesterol would indicate an excess or lack of this substance, the discordance between these two data would correspond to an offbalance. A high cellular, with a relatively normal or low plasmatic cholesterol, corresponds thus to an abnormal cholesterol offbalance predominant at the cellular level, while a relatively low cellular and high plasmatic cholesterol, to the opposite offbalance. By now considering cholesterol in its anti fatty acid role, these changes permit further interpretation.

As we have seen above, cholesterol corresponds rather to the anti fatty acid constituents controlling the normal polyunsaturated fatty acids and thus differs from the corticoids which represent agents opposing the abnormal fatty acids. The ultimate cause of hypercholesteremia would logically be sought in a quantitatively abnormally high amount of qualitatively normal fatty acids present at the lower levels.

Although hypercholesteremia represents by itself only a response to a fatty acid offbalance taking place at lower levels, the high amount of sterol present in blood can cause, by itself, a series of disagreeable manifestations. Hypercholesteremia can thus induce noxious manifestations although, tele ologically speaking, it is directed to correct an offbalance at a lower level. The effect of this chronic richness in blood cholesterol is manifested in the circulatory system and atheromatosis appears as an immediate result. The precipitating tendency for any new increase in blood cholesterol explains the appearance of crystals in the cells of the intima and secondarily the appearance of atheromas.

Therapeutic Attempts

This pathogenic concept of arteriosclerosis presented above, has guided our therapeutic approach. As early as 1942, we used acid lipidic fractions of organs in a tentative therapy to control hypertension and indirectly arteriosclerosis, with interesting immediate results. We learned however, that not only were the effects temporary but also that after some time, the administration of unsaturated fatty acids induced a progressive increase in the amount of cholesterol present in blood.

The concept of hypercholesteremia as a secondary blood response to a cellular fatty acid predominance explained this occurrence and led us also to the further development of this approach. With cholesterol as an anti fatty acid agent which appears in high amounts in blood, as a response to an excess of fatty acids at the cellular level, we tried to influence this secondary response by acting on the existing primary cellular offbalance. A decrease of this response could be obtained by supplying substances other than cholesterol, acting as anti fatty acid agents. If the cellular fatty acid offbalance can be controlled, the organism as an entity would no longer be obliged to respond to the occurring offbalance and manufacture blood cholesterol in excess. Without this need, hypercholesteremia will no longer appear. Under these conditions, the administration of anti fatty acids has appeared as the logical way to prevent and even to combat an existing hypercholesteremia and its consequences.

Choice Of The Anti Fatty Acid Agent

The next problem was the choice of an adequate anti fatty acid agent. It appeared advisable to use more than one such agent. One would intervene at the lower cellular level where the primary factor—predominance of fatty acids—exists; another would act at the level of the tissue and blood itself where their presence would act as an anti fatty acid and prevent more directly the further appearance of cholesterol.

These considerations led us to utilize as active agents, heptanol, glycerol and polyunsaturated alcohols for the tissue level. Butanol was added, being more active at the organ and systemic levels. We found that mixtures of these alcohols were advisable also in view of the plurality of fatty acids intervening in this abnormal condition. Mixtures of polyunsaturated fatty alcohols were obtained through treatment with lithium aluminum hydride, of the fatty acids present in cod liver oil, fish oil, safflower oil, sesame oil, or even in the lipoacid fraction of organs.

Clinical Results

The best clinical results were obtained with a preparation having in its constitution, glycerol, polyunsaturated fatty alcohols, heptanol and butanol. In a series of subjects with persistent high amounts of cholesterol in blood, the administration of this preparation brought the blood cholesterol to low values. The following observations are characteristic.

Mr. M. R., 60 years old, had high cholesterol in the blood for ten years, with values above 350 mgr. %, in spite of severe diet poor in fats and cholesterol. Administration of unsaturated fatty acids brought the blood cholesterol, for a short time, to values between 260 mgr. and 300, returning to values above 350 after cessation of medication. Wtih the mixture—glycerol, polyunsaturated fatty alcohols, butanol and heptanol—the blood cholesterol went down to 150 mgr. % in less than two weeks without any side effects or restricted diet, and with a manifestly good general condition. It remained at this level for the 5 months of observation with only minimal and irregularly taken medication.

L. N., 70 years old, with blood cholesterol varying in recent years between 400 mgr. and 280 mgr. in spite of low fat and low cholesterol diet and different treatments. The mixture of glycerol, fatty alcohols, heptanol and butanol, brought it down in three weeks to 160 mgr. It remained around this value for more than the six months of observation with no special diet and with only a very small amount of medication.

In a group of 20 subjects with cholesterol above 350 mgr. %, a descent of the cholesterol to values below 250 mgr. % was obtained in all the cases, with a treatment ranging from 10 days to 3 weeks. No inconveniences were observed.

Coronary Occlusion

The coronary occlusion with the consequent myocardial infarction represents the most important complications of arteriosclerosis. Death can occur instantaneously. In these cases it can be considered to result from a lesion of such localization or dimension as to be entirely incompatible with the function of the heart. When death occurs, not instantaneously but at any time after the occlusion has taken place, other factors have to be considered as intervening and leading to the fatal issue. Shock appears to be the most important one. Superacute shock, with death in a few minutes, an acute shock with death in 1-2 hours, or state of shock with death within hours or days, represent the other important intervening pathogenic factors added to the infarction itself. As seen above, these types of shock correspond to offbalances of the type D, this time with a predominance of abnormal lipoacids. A therapy with anti fatty acid agents represents as shown above, the intervention which could prevent or reduce shock. While the administration of sterols appears contra indicated, since it would increase the vascular occlusion, that of the non sterolic anti fatty acids is especially advisable.

The effect of these anti fatty acid agents upon pain and the other symptoms which are of alkaline pattern, as well as upon the evolution of the condition, has fulfilled our expectations. We attributed an important role to glycerol in these cases. Its action similar to an anti coagulant but limited to the level of the existing lesions, was able to prevent further local thrombosis without, however, the danger of a general reduction of blood coagulability. Administered in adequate amounts, guided by the pattern analyses, the mixture of the anti fatty acid agents mentioned above has been followed by manifest clinical improvements.

L. K., 58 years old, with a history of several myocardial infarctions, was seen in a very severe state of shock. The electrocardiogram showed that besides the old lesion in the posterior wall, a new infarction of the anterior wall was present. Butanol was administered in doses of 5 cc. of the 6.5% solution together with 0.1 cc. glycerol every hour until the complete cessation of symptoms and was continued 4 times a day afterward. The favorable effects continued in an unexpected form, the patient being without pain in less than 3 hours and without symptoms the third day. The cholesterol was found to be 135 mgr. % the fifth day.

This view of arteriosclerosis opens a new way for further research concerning many pathogenic problems, and a logical therapeutic intervention in this condition.