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The cardiac effects of serotonin were studied in 20 young mongrel dogs. Serotonin was slowly infused through a catheter inserted into the left carotid artery with the tip of the catheter located 1 or 2 cm. above the coronary orifices. The doses for different groups of dogs were 10, 5, 2, and 1 mg. in 500 cc. of normal saline, three to six times each week. The period of infusion lasted one to six weeks. A group of four dogs acted as controls. In dogs treated for more than two weeks with doses of 10 to 5 mg., and in those treated for more than four weeks with doses of 2 mg., the following pathological findings were observed: (a) fibrotic thickening of mitral, aortic, and tricuspid valves in this order of frequency; (b) myocardial hemorrhages partially organized; (c) focal ischemic necrosis of myocardium with or without round cell infiltrations; (d) intimal thickening of small coronary arteries either in the form of cushions bulging into the lumen or extensive subendothelial thickening with asymmetrical reduction of the lumen. The intima of these arteries showed either an acellular homogeneous substance or a fibroblastic proliferation and fibroelastic hyperplasia. These findings were considered to be related to a direct action of serotonin which plays some role in the connective tissue function.

Coronary Arteriosclerosis Induced in Young Dogs by Prolonged Intra-aortic Infusions of Serotonin