Experiments with calculated therapeutic and toxic doses of digitalis: II. Effects on the electrocardiogram

Abstract

Calculated therapeutic amounts (20 or 30 per cent of minimal lethal dose) of digitalis, in single doses, or in divided doses over a period of forty-eight hours, produced the following types of RS-T segment and T-wave changes: (1) No significant change; (2) positive T 3 changed to negative T 3; (3) negative T 3 changed to positive T 3; (4) decrease of height of T wave in one or more leads; (5) increase of height of T wave in one or more leads. Similar electrocardiographic patterns were noted when animals were digitalized rapidly with a calculated therapeutic dose of digitalis and then were given daily doses which were estimated to be equivalent to 1 or 2 cat units a day for a 70-kilogram man. The electrocardiographic studies were made during experiments which lasted from six to fifty-six days. Myocardial lesions were not observed in any of these two groups of animals. In our experiments there were no constant changes in the RS-T segment or T wave which could be taken as a reliable index to the presence of a calculated therapeutic amount of digitalis. The cardiac rate was also unreliable; a therapeutic dose of digitalis produced an increase, decrease, or no change in the cardiac rate over a period of days. Toxic amounts of digitalis, when administered in single doses (40 to 80 per cent of the minimal lethal dose), or when given daily to digitalized animals in an amount which corresponded to 3,4 5.5, or 6 cat units for a 70-kilogram man, produced the following electrocardiographic alterations: (1) no significant change; (2) positive T 3 changed to negative T 3; (3) decrease of height of T wave in one or more leads; (4) increase of height of T wave in one or more leads; (5) depression of the RS-T segment in one or more leads; (6) change in the RS-T segment, the initial portion of which began above the isoelectric position and the terminal portion of which ended below the isoelectric line; (7) elevation of the RS-T segment (“plateau type”) in one or more leads; (8) cove-plane, negative T 2 and T 3, with positive T 1; (9) cove-plane, negative T 1 and positive T 2 and T 3. Changes (1) to (5), inclusive, were usually not associated with myocardial lesions, whereas patterns (6) to (9) were associated with myocardial lesions produced by digitalis. Two animals that had microscopic evidence of myocardial lesions failed to show any significant changes in the daily electrocardiograms. The electrocardiogram returned to normal in all animals which did not die spontaneously or were not killed for experimental reasons. The electrocardiograms returned to normal while microscopic evidence of active inflammation persisted in the myocardium. The electrocardiogram was normal in those animals in which the myocardial lesions had healed (focalized zones of fibrosis).