STUDIES ON THE PATHOGENIC EFFECTS OF DRUGS


In guinea pigs and rabbits the isolated intestine perfuses in Tyrodes solution showed little or no change in amplitude and frequency of contractions. The general tonicity diminished, allowing the intestines to relax. This might be an explanation of the symptom “Great distention of the abdomen.” The isolated bladder showed a similar action except that the frequency of contraction diminished until it was lost in the general relaxation.


 From the Department of Medicine and Homoeopathy, New York Homoeopathic Medical College and Flower Hospital, New York City.

SECOND PAPER – ABROTANUM.

Abrotanum is a drug little used in the practice of medicine and a detailed study of the literature fails to reveal any information which can serve as an explanation of its occasional use. A glance at any homoeopathic textbook of therapeutics will show a wide range of applications, Cowperthwaite stating that the drug may be useful in marasmus of children, wasting diseases from malnutrition, rheumatism especially before swelling, gout, gastralgia, also the bad effects of suppressed gastralgia, hydrocele of children, chlorosis, furuncles, that it acts upon the fibrous and serous tissues, produces a hyperemia of the nervous system and gives rise to anaesthesia and paralysis.

Either the drug has an extremely wide application and is undeservedly neglected, or the applications are few and misunderstanding has limited and narrowed the range until it is rarely used. With these thoughts in mind we thought it advisable to determine whether or not the drug was sufficiently valuable to excite renewed interest.

We first examined the drug as to activity. With guinea pigs one series of animals received five cc. doses of the drug and after four doses (one daily) died presumably from the effects of the drug. Another group received twelve doses of 5 cc. without any apparent effect, but died after a single dose of 10 cc. The same general effect is seen in rabbits. We conclude that the drug is only slightly active in guinea pigs and rabbits.

In regard to loss of weight and emaciation (as suggested by the materia medica) the average loss in the first group was 30 grams, in the second group 60 grams. As controls, animals receiving Abies Nigra lost 210 grams in weight.

In guinea pigs and rabbits the isolated intestine perfuses in Tyrodes solution showed little or no change in amplitude and frequency of contractions. The general tonicity diminished, allowing the intestines to relax. This might be an explanation of the symptom “Great distention of the abdomen.” The isolated bladder showed a similar action except that the frequency of contraction diminished until it was lost in the general relaxation.

The isolated non-pregnant uterus showed a tetanic contraction after the first application, while a second application in a smaller dose merely increased the tonic contraction.

The action upon the isolated heart-Langendorf preparation – Lockes solution, was as follows:.

0.1 cc. – In three seconds a falling off of amplitude lasting thirteen seconds with recovery in twenty seconds. The rate is slowed four beats per second seconds and upon recovery gains back only two in the same period.

0.2 cc. Amplitude and rate lessened and slow with recovery as under 0.1 cc.

0.5 cc. The amplitude is lessened to almost zero. Rate slowed six beats. The recovery takes 50 seconds as regards rate while the amplitude recovers about 80 per cent.

1.0 cc. The heart is topped four seconds after the drug is perfused and the block lasts thirty-three seconds with recovery in fifty seconds as under 0.5 cc. 1.5 cc. same as 1.0 cc.

EFFECTS OF ABROTANUM INTRAVENOUSLY IN RABBITS.

0.2 cc. 0.4 cc 0.6 cc 1.0 cc.

Blood No Change Drop of 2 mm. Inc. Slowly Dropped 4

Pressure 7mm. in 60 mm. in 18.

seconds. sec., then. inc.

Respiration No change Inc. rate for Slowed to Slowed.

in amplitude 12 sec. normal. Amplitude.

Slightly.

increased.

Irregularity.

in rhythm.

Left No change Slightly No change in In 14 Sec. Ventricle slowed. No rate, rhythm. change.

change in Amp.increased. Marked

force of inc. rate.

rhythm. and decrease.

in amplitude with.

recovery

in.

44 sec.

Left Slightly Same. Same as.

slowed. Amplitude above.

increased.

Time 14 sec. Action Began in 3.

began in seconds.

5 seconds. Lasted 60. seconds.

1.5 cc. 2.0 cc. 3.0 cc. 5.0 cc.

Blood Inc. with Same Same Rapid drop

Pressure rapid fall. to neg.

pressure.

Respiration During inj. Increased Same Increased

increased rate during with.

then slowed inj. injection of.

with recovery drug.

stopped.

after.

Left Rapid Same Same Rapid

Ventricle depression change, i.e.,.

in rate and depression in.

amplitude with rate, rhythm.

recovery. and force with.

cardiac failure.

Heart stopped.

in diastole.

Left Same Same Same No change with

Auricle. cutting vagi.

Time. 6 sec. 6 sec. 6 sec. 6 sec.

Examination of these statements shows that the principal effect of the drug is exerted upon the heart and respiration. Application of the drug in increasing doses causes first slight slowing, while large doses increase the rate with a diminution of amplitude while still larger doses cause a depression of the rate. This is a local action as seen by a comparison of the isolated heart findings with the intravenous, and the lack of appreciable change following section of the vagi. The auricle follows the ventricular changes to a less degree, so that the brunt of the action is upon the muscles of ventricle.

The effect upon respiration is exactly opposite to the effect upon the heart, while blood pressure follows closely the output of the ventricles. It would seem that there is ground for the production of cardiac symptoms following the administration of the drug. The end result is slowing, with lessening of the blood pressure, so that “small weak pulse” can be confirmed. It is also known that the heart rate after acute rheumatic fever is slow in a great majority of cases where there is any change. In short from the standpoint of function the effect of rheumatic fever and Abrotanum is not dissimilar. Whether an analysis of the electrocardiographic curves would further this the writer cannot state.

It is well known that the virus of acute rheumatic fever is characterized by a special tendency to involve the heart. The involvement of the heart is usually shown by the formation of the Aschoff body, as well as a pancarditis of varying intensity. We therefore thought it advisable to intoxicate animals in order to determine whether or not any changes could be found in the peri- myo-or endocardium. This was done with dose suggested in the paragraphs above (second paragraph).

In no instance were we able to find any change in these structures. In fact, the chief finding in the entire autopsy was passive congestion, which was expected from the findings with the Langendorf and the intact heart, blood pressure and respiration preparation. No studies were made upon the blood so that no comment can be made upon a similarity to gout, chlorosis, etc. Unfortunately the sections of the spinal cord were not satisfactory so that no report can be made upon this structure, although it should be noted that the brain showed only passive congestion.

Conclusion: Abrotanum has a marked cardiac action characterized by changes in function rather than structure, in guinea pigs and rabbits. The action upon the uterus is new and deserves further investigation by provings and laboratory work. The remedy probably has a definite field of activity which at present is not utilized.

Linn J. Boyd