First Treatment Methods for Atherosclerosis

Up to the 1960s, the treatment of atherosclerosis was only symptomatic. [363] Thus, for example for lowering blood pressure, there was used an extract from the snake-shaped roots of Rauwolfia serpentina, which was already known to the ancient Hindus (Fig. 5.149). [364] In 1952, EmU Schlittler (1906-1979) of the Ciba company isolated reserpine as its hypotensive principle, and determined its constitution. In particular, he also recognised the relationship to the large class of yohimbine alkaloids. The first constitutional total synthesis was achieved in 1956 by R. B. Woodward. [365-367] It counts as one of his most notable contributions to modern synthetic chemistry and formed the basis of industrial processes for the synthesis of this drug. In 1989, Gilbert Stork published a stereospecific total synthesis. [368] 

Another drug, which was assumed to intervene in the metabiolism of lipoprotein or cholesterol, was heparin. Nowadaj we know that heparin indeed releases a lipoprotein-lipase from the sruface ofvascular endothelial cells, which then dissolves triglycerides in the chylomicrons and VLDL. 

Henry Howell (1860-1945) and is extracted nowadays from the mucous membranes in the small intestine of pigs, or from the lungs of cattle. The drug inhibits the transformation of fibrinogen into fibrin, and is now used for the treatment of thromboses, embolisms and for the prophylaxis of cardiac infarction and thrombosis. A disadvantage is, that heparin is not resorbed from the gastrointestinal tract, and has to be administered via an intravenous, subcutaneous or percutaneous route. 

In 1955, nicotinic acid (vitamin B3, niacin) moved into the focus of research as a drug to lower cholesterol levels. The Canadian psychiatrist Abram Hoffer (1917-2009) had achieved good results with nicotinic acid in the treatment of schixophrenic patients. [369] 

However, as a side-effect of the therapy, his patients suffered from a massive flush syndrome (harmless but mostly unpleasant reddening ofthe skin on the face, neck, chest and upper arm). For a better assessment, Hoffer himself took gram quantities of niacin over several months, and discovered to his surprise that this treatment had healed his serious inflammatory gum disease. Inspired by Rudolf Virchow s hypothesis, that atherosclerosis was an inflammatory process, which was associated with serum cholesterol, Rudolf Altschul (1901-1963), Hoffer s former histology teacher, demonstrated in his hypercholesterolemic rabbit model, that within a few days niacin brought cholesterol levels back to normal. This prompted corresponding studies by Hoffer in the psychiatric patients. 

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