The Effects of Strophanthin and of Digitalis.

1. In intact dogs the dose which caused slowing and other signs of vagus stimulation without causing ectopic contractions usually lay between 30 and 40 per cent of the minimum lethal dose for Thoms g-strophanthin and for digipuratum and a fluid extract of digitalis, given intravenously in dilute solution in about 15 minutes.

2. In dogs strophanthin and digitalis when given intravenously produced typical alterations in the electrocardiogram almost immediately and with equal rapidity.

3. In this series the changes in the electrocardiogram following the administration of 25 to 40 per cent of the minimum lethal dose of strophanthin or digitalis often passed off within an hour or two and with few exceptions were not visible in electrocardiograms taken 20 hours later. The effects of digitalis did not appear to be more lasting than those of strophanthin. As there were marked differences in the persistence of the action of each of these drugs within its own series, this conclusion is provisional.

4. A persistent auriculoventricular block (without the occurrence of ectopic beats) was obtained only exceptionally, but the administration of 30 to 40 per cent of the minimum lethal dose of either of these drugs was usually followed by the occurrence either singly or together of occasional auriculoventricular blocks or exaggerated sinus arrhythmia or sinus block, and by pronounced slowing of the sinus rate.

5. Occasionally, with or without previous slowing or the occurrence of ectopic beats, these doses caused a marked acceleration of the sinus rate.

6. The auriculoventricular (P-R) time was usually lengthened but may be shortened.

7. The P wave may become less positive, isoelectric, or negative.

8. The T wave most often became negative before or during the stage of slowing but frequently became or remained positive during this stage. When the sinus rate increased or when occasional ectopic beats occurred, this wave almost always became decidedly more positive. At times it varied rapidly and decidedly within a period of a few seconds.

9. Ectopic ventricular beats occurred in a number of instances after doses ranging from 19 to 40 per cent of the minimum lethal dose, and usually but not always when more than 40 per cent had been injected within 15 to 30 minutes.

10. Previous administration of either of these drugs did not appear to cause either a quantitative or qualitative alteration in the reaction of the heart to amyl nitrite or atropine (with the exception that such previous administration appeared responsible for the fact that in one experiment the inhalation of amyl nitrite, and in two others the injection of atropine, was followed by the occurrence of ectopic beats).

The Effects of Amyl Nitrite.

1. In intact dogs, both before and after the administration of strophanthin or of digitalis, the inhalation of amyl nitrite usually caused at first (probably largely reflexly) a pronounced increase of vagus tone shown by slowing of the sinus rate) exaggerated sinus arrhythmia, or auriculoventricular block. Later the sinus rate was accelerated and arrhythmia or blocks disappeared (probably due to vasodilatation and diminished vagus tone).

2. The auriculoventricular (P-R) time was usually lengthened at first and later was shortened.

3. The P wave often at first became shorter, isoelectric, or negative, but later became much more positive.

4. The T wave at first often became less positive or more negative, but later became strongly positive.

5. When the previous administration of not too large doses of strophanthin or digitalis caused the occurrence of ectopic ventricular beats, the inhalation of amyl nitrite usually caused their temporary disappearance. Even when large doses of these drugs caused a constant succession of ectopic contractions of various types, its inhalation was often followed by a temporary return of nomotopic cycles or by a change in the form of the ventricular complexes so that they more closely resembled that of nomotopic ones.

6. Only large amounts of amyl nitrite appear to have the power to prevent ectopic ventricular beats or to alter their type.

The Effects of Atropine.

1. In intact dogs before and after the administration of strophanthin or digitalis, smalf doses of atropine usually caused auriculoventricular block (or exaggerated it if already present). Larger doses, after first producing the same effect as the small ones, caused an increased sinus rate and abolished blocks or sinus arrhythmias if present.

2. The P-R time was usually lengthened by small doses and shortened by larger ones.

3. The P wave sometimes became shorter at first (less positive), isoelectric, or negative, but later (when the peripheral vagus paralysis ensued) it became positive again, often much more so than it was originally.

4. When ectopic contractions were present as a result of previous administration of strophanthin or digitalis, atropine, like amyl nitrite, often caused their disappearance, or altered the form of the ventricular complex, but was less efficient in this direction than amyl nitrite.

5. Occasionally the injection of atropine into dogs, which had previously received strophanthin or digitalis, appeared to facilitate or bring on the occurrence of ectopic ventricular contractions.

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