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Title: Some experimental and clinical experiences with the use of rubellin, a new digitalis-like drug, in heart disease
Author: Isaacson, Barnett
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1949
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(1) The results of a series of preliminary experiments on the effects of Rubellin, a new digitalis -like drug, on cats and human subjects are described. As far as is known, this is the first and only report on the clinical use of Rubellin in man. (2) Rubellin, a new cardiac glycoside of South African origin, is a purified crystalline preparation, the potency of which has been established. It has the advantage that the dose can be measured gravimetrically and need not be assayed biologically. Electrocardiograms were recorded before and after the administration of the drug. (3) Experiments are described on cats which confirm the work done by Sapeika (1944), showing that Rubellin has a digitalis-like action. Toxic doses of the drug produced impure auricular flutter, ventricular paroxysmal tachycardia and widening of the QES complex, while amounts considered as therapeutic produced a decrease of the cardiac rate without significant changes in the configuration of the complexes. (4) In the experiments on human beings, a total of 43 intravenous injections of Rubellin was given to 14 patients, most of whom were in severe congestive cardiac failure. These included 6 injections of 0.42 mg.; the rest were injections of 0.21 mg. These were diluted in 10 ces. sterile saline or distilled water. One death occurred 21 hours after a single injection of 0.21 mg. This case had aortic disease and was in a moribund condition on admission to hospital. (5) The 14 patients consisted of:- 8 cases (1,3,4,6,7,9,10,11) suffering from hypertensive cardiac disease. Case 7 had bronchial asthma superadded. 2 cases (2 and 14) suffering from cardiovascular syphilis. 1 case (5) suffering from rheumatic heart disease. 1 case (8) suffering from myocardial disease following coronary thrombosis. 1 case (12) suffering from arteriosclerosis. 1 case (13) suffering from bronchial carcinoma with metastatic deposits in the heart. 8 of the 14 cases had normal sinus rhythm. (2,4,5,6,7,10,11,14) 4 of the 14 cases had auricular fibrillation. (1,3,8,9) 2 of the 14 cases had auricular flutter. (12,13) 12 of the 14 cases were in congestive cardiac failure. (1,2,3,4,5,6,7,8,9,10,11,14) (6) Rubellin was found to be efficient in both normal and abnormal rhythm, acting with best results in auricular fibrillation and congestive cardiac failure. When given intravenously it alleviated all urgent symptoms within a very short space of time, thus greatly reducing the period of suffering. It has been shown that the persistence of effect could last up to 19 days. (7) Rubellin produced a decrease of the heart rate in 12 cases, the most marked being:- Time // Decrease in Heart Rate // Dose: 10 mins. (Case 8) // 17 beats // 0.21mg. 10 mins. (Case 4) // 20 beats // 0.42mg. 15 mins. (Case 6) // 24 beats // 0.42mg. 15 mins. (Case 9) // 26 beats // 0.21mg. (divided doses) 30 mins. (Case 13) // 30 beats // 0.42mg. 60 mins. (Case 4) // 32 beats // 0.42mg. 60 mins. (Case 9) // 40 beats // 0.21mg. 9.25 hrs. (Case 8) // 57 beats // 0.42mg. (divided doses) 11 hrs. (Case 3) // 54 beats // 0.42mg. (divided doses) 25.25 hrs. (Case 8) // 85 beats // 0.63mg. (divided doses) (8) While Rubellin, in its speed of action, was found to approach strophanthin and digoxin intravenously, in its effect on the electrocardiogram, however, it resembled digitalis. The P wave was reduced in height from 3.5 mm. to 2.0 mm. in one patient (Case 4) following 1 injection of 0.42 mg. The P -R interval was prolonged in 3 cases, in one instance to as much as 0.32 secs. QRS - no appreciable changes were noted in these complexes. S -T segments were depressed in 8 cases. There was inversion of the T waves where T was originally upright and restoration to the upright position where T was originally inverted, in 1 case (Case 8). Extrasystoles were noted in 3 cases in which bigeriinal rhythm was present. The Wenckebach phenomenon was produced in 2 patients (Cases 5, 6). Auricular fibrillation was produced in 1 patient (Case 2). In 2 cases of auricular flutter, while the ventricular rate was decreased in both, the rhythm changed from a regular to an irregular block in one of them. (9) There was a decrease in venous pressure in 7 readings in 6 cases of congestive failure where these were taken before and after treatment with Rubellin. There was a decrease in the circulation time in 5 instances in 4 cases and an increase in 1 case (Case 5, sxpt.3). (10) Loss of weight took place in 5 cases of congestive cardiac failure where the weights were recorded before and after treatment. (11) Reduction in size of the heart was noted radiologically in 1 patient (Case 1). (12) The toxic effects of Rubellin were not greater than those of digitalis. (13) Experience suggested that in cases of severe advanced congestive cardiac failure, a single dose of Rubellin administered intravenously is capable of producing full action within 2 hours. Digitalis by mouth could be given simultaneously. Rubellin has a quick action which lasts until the oral digitalis begins to take effect. Rubellin would appear to be of value in cases of vomiting and unconsciousness and where immediate treatment of congestive cardiac failure is imperative, provided it is certain that no other digitalis body has been taken within the preceding 10 days. (14) At this early stage, comparison of Rubelhin with Strophanthin or digoxin for use intravenously in cardiac emergencies is not attempted. It is realised that there are other preparations of digitalis and digitalis bodies on the market suitable for intravenous use. Further clinical study is necessary before venturing an opinion on the possible clinical usefulness of Rubellin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available