Haemodynamic effects of angina pectoris, and of nitroglycerin in normal and anginal subjects.

Though the nitrate drugs have been widely used to alleviate or prevent angina pectoris for nearly 100 years, the mechanism of their action remains unknown. The two possibilities that have been most widely considered are (a) that they cause an increase in oxygen supply to the heart through coronary vasodilatation and increase in coronary flow, and (b) that they cause a reduction in energy expenditure of the ventricular muscle. The evidence in support of these two possible mechanisms is confusing. While there is no doubt that administration of nitrate preparations to experimental animals may well result in increased coronary flow (Wegria et al., 1940; Griggs, Pierson, and Case, 1961), these changes are short lived. They are not demonstrable in human patients suffering from angina pectoris (Gorlin et al., 1959) nor can the administration of such drugs in therapeutic doses be shown to cause any change in coronary sinus oxygen content (Gorlin et al., 1959; Brachfeld, Bozer, and Gorlin, 1959; Rowe et al., 1961). However, the pain and electrocardiographic changes may be prevented when nitroglycerin is administered before the performance of a load normally capable of causing angina (Kinsella, Troup, and McGregor, 1962; Sosa and McGregor, 1963), and this effect is demonstrable as long as 30 minutes from the time the drug is taken (Bunn and Chremos, 1963). The failure to demonstrate consistent increase in coronary flow at this time interval is thus probably more relevant than the transient increments of flow observed in animal experiments.