Until recent years the various xanthine derivatives were employed in the treatment of cardiac disease chiefly because of their diuretic action. The discovery that these preparations cause dilatation of the coronary arteries and the introduction of theophylline ethylenediamine in 19081 led to a further study of this particular pharmacologic action.
Eppinger and Hess2 observed a stretching of strips of coronary arteries when they were placed in a solution of caffeine, and Gow,3 employing a similar method, noted a dilatation of arterial rings taken from the renal and splenic arteries. Hedbom4 was among the first to study the problem by the perfusion method and reported an increase in the coronary flow with caffeine in a concentration of 1:20,000. Loeb5 observed a marked increase in the rate of perfusion with theobromine but very little effect with caffeine. Heathcote,6 working with caffeine, theobromine and theophylline in concentrations from 1:2,000
FOWLER WM, HUREVITZ HM, SMITH FM. EFFECT OF THEOPHYLLINE ETHYLENEDIAMINE ON EXPERIMENTALLY INDUCED CARDIAC INFARCTION IN THE DOG. Arch Intern Med (Chic). 1935;56(6):1242–1249. doi:10.1001/archinte.1935.00170040176009
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