Arthur C. DeGraff

Comparative study on the use of the purified digitalis glycosides, digoxin, digitoxin, and lanatoside C, for the management of ambulatory patients with congestive heart failure

Abstract 1. 1. Comparative studies on three purified digitalis glycosides, digoxin, digitoxin, and lanatoside C, were performed in a group of seventy-four ambulatory patients. 2. 2. For reasons of safety in administration and satisfactory maintenance, digoxin is the glycoside of choice. 3. 3. Lanatoside C administered orally is not satisfactory for the routine daily management of the patient with congestive heart failure. 4. 4. Other than the assurance of obtaining uniformity in various lots, the glycosides have no particular advantage over digitalis leaf. 5. 5. The incidence and degree of toxic symptoms is the same for the three glycosides. The duration of toxicity is much greater with digitoxin than with lanatoside C or digoxin.

The combined use of ouabain and digitalis in the treatment of congestive heart failure

Abstract 1. 1. A method of obtaining rapid digitalization by the simultaneous administration of ouabain intravenously and digitalis leaf orally is presented. 2. 2. Digitalization was produced sixty times in fifty-nine cases. The patients had varying degrees of congestive heart failure and different types of heart disease; their ages ranged from 28 to 70 years. 3. 3. In the majority of the cases, improvement occurred within one hour. This improvement, once established, was progressive; the maximum effect was attained at the end of twenty-four hours. 4. 4. After the initial digitalization, it was not difficult to establish the maintenance dose of digitalis leaf. 5. 5. The method was found to be applicable to patients with normal sinus rhythm, as well as to those with auricular fibrillation. 6. 6. Evidences of toxicity were the least that could be expected, indicating that the method is a safe one.

Reaction at Site of Injection of Mercurial Diuretics as Influenced by Theophylline

The comparative toxicity of mercurial preparations has usually been studied from the point of view of “minimal toxic dose” in the sense of causing death in a fixed period of time. The literature on this subject has been fully reviewed by Fourneau and Melville. 1 However, very little attention has been paid to the local reaction at the site of injection. The frequent occurrence of venous thrombosis and necrosis from the use of mercurial diuretics is of considerable importance. v. Issekutz and v. Vegh 2 combined a mercurial diuretic with theophylline and suggested that the latter, having weak acidic properties, neutralized the alkaline reaction (responsible for the pain) that is produced upon hydrolysis of the mercurial salt. This combination was introduced as novurit, but is known in this country as mercupurin.∗ Recently Fulton and Bryan 3 found that in animals both salyrgan and mercupurin produced definite necrotic lesions, but the former was more severe in extent and degree of reaction. They noted that there was a striking absence of slough formation when a mercurial salt, to which 5% theophylline was added, was injected subcutaneously. We have compared the local action of mercurial diuretics with and without theophylline and have attempted to establish a quantitative relationship. The preparations used were mercupurin, the theophylline-free mercurial salt contained in mercupurin, salyrgan, salyrgan plus aminophylline (so that the theophylline content was equivalent to that of mercupurin) and as a control—aminophylline, physiological saline and distilled water.∗ Equivalent amounts of the drugs as regards mercurial content were used. The following series of experiments were performed: (1) Doses of 0.05 cc. of various dilutions (undiluted to 1:100) of the drugs were injected intracutaneously into the abdominal wall of 12 rabbits. Each rabbit was given at the same experiment the various dilutions of at least 3 diuretics and the control drugs.

Excretion of Mercury Following Administration of Mercurial Diuretics with and without Theophylline

It has recently been shown that the addition of theophylline to the mercurial diuretics Mercurin and Salyrgan practically prevents their local toxic action 1 2 and promotes their absorption after intramuscular injection. 3 Although Mercupurin (Mercurin with theophylline) has been found to have a somewhat greater diuretic efficiency than Salyrgan, 4 5 6 7 it remains to be proven unequivocally, however, that theophylline exerts any influence after the drug has reached the circulation. It was therefore decided to study the excretion of mercury by laboratory animals after the administration of these diuretics with and without theophylline. It is fully realized that results thus obtained cannot necessarily be referred to man. Nevertheless, it was felt that information concerning the pharmacology of drugs of this type could more readily be obtained by using animals whose food, salt and water ingestion could be kept perfectly constant. A total of 24 albino rabbits weighing between 2 and 3 kg were used in these experiments. All the animals had been raised on a diet of alfalfa hay and oats and had received a constant daily supply of water. On the day of the experiment each rabbit was tied to an animal board and 75 cc of water at body temperature administered by stomach tube. One hour later the animal was catheterized (French No. 10 catheter), the urine discarded and 0.10 cc of the drug to be studied was injected with a tuberculin syringe and 26 gauge needle either into the tibialis anterior muscle or one of the marginal veins of the ear. This was equivalent to 3.71 mg of mercury in the case of Salyrgan or Salyrgan with theophylline and 3.80 mg in the case of Mercurin or Mercupurin. The catheter was strapped in place with adhesive tape and all the urine excreted within the next 6 hours collected in 25 cc graduates. Since the rates of excretion vary considerably for the different drugs and methods of administration, it was necessary to space the collection of samples so that the time at which maximum excretion occurred could easily be determined.

Effect of Hypoadrenalism and Excessive Doses of Desoxycorticosterone Acetate upon Response of the Rat to Ouabain

The influence of alterations of adrenal function upon the responsiveness of the rat to intravenously administered ouabain was studied electrocardiographically by the string galvanometer. Conduction disturbances followed by cardiac arrest were the criteria for a definitive response. Adrenalectomized rats showed a significant increase in sensitivity to ouabain as compared with normal controls. Normal animals implanted with pellets of desoxycorticosterone acetate and continuously maintained on saline drinking water did not show a significant alteration in their responsiveness to ouabain.

Limiting Content of Theophylline Necessary to Prevent Local Toxic Action of Mercurial Diuretics

In a previous paper 1 it has been shown that theophylline greatly diminishes the toxicity of Mercurin∗ and Salyrgan at the site of intracutaneous injection. The beneficial action of theophylline in enhancing absorption after intramuscular injection has also been demonstrated 2 and it was found 3 that one mole equivalent (3.88% of theophylline monohydrate) produces the maximum effect. Since this and other data 3 are strongly suggestive of compound formation between theophylline and mercurial diuretics of general structure NaOCO-RII-HgOH it seemed advisable to determine the limiting amount of theophylline necessary to prevent local toxicity. The experimental procedure was the same as that described before 1 and consisted in the intradermal injection into the abdomen of the rabbit of 0.05 cc. of Mercurin and Salyrgan to which varying amounts of theophylline had been added. Each solution was prepared to contain 39 mg. of mercury per cc. (about 0.2 M) and its pH was accurately determined with the glass electrode. In the accompanying photograph, taken 24 hours after injection, the mole equivalents of theophylline and pH values for each of the 7 solutions are shown adjacent to the corresponding sites of injection. In all 5 rabbits were injected in this way for Mercurin and 3 for Salyrgan. The results for the 2 drugs are very much alike and were found to be so consistent that only one photograph is shown. It will be seen that the local toxicity decreases in proportion to the amount of theophylline present and in the case of the solutions containing 1, 1.25, and 1.5 mole equivalents, so little reaction was produced that it is difficult to locate exactly the sites of injection.

Thyroid Analogs as Cholesteropenic Agents

Thirty-six patients with casual serum cholesterol levels above 250 mg per cent were recruited. Patients were not eliminated, if subsequent baseline cholesterol fell below this level. Six patients with arteriosclerotic heart disease were included. During the baseline period, the patients were interviewed, their hospital records were abstracted, a physical examination was performed, and the initial laboratory studies were obtained. The latter included at least 2 fasting serum cholesterol determinations (method of Schoen-

Fate of the Lethal Effect of Sublethal Doses of Lanatoside C, Digoxin and Diǵoxiǵenin

Conclusions The lethal effect of lanatoside C dissipates rapidly

Rapid ventricular rhythm produced by pressure over the precordium report of a case

Abstract 1. 1. A case is reported in which a rapid ventricular rhythm is produced by pressure over the precordium. 2. 2. The stimulus appears to be a direct pressure effect on the heart, and not a cutaneous reflex phenomenon. 3. 3. The ventricular rate is higher than the auricular rate (ventricular rate 170 per minute, auricular rate 80 per minute). The auricular rate is the same as that before the ventricular rhythm was produced and is in response to the sino-auricular node. 4. 4. Forward conduction is unimpaired as shown by the appearance of normal ventricular complexes in response to the auricular beats which reach the ventricle when it is not refractory. 5. 5. Stimulation of the vagus tends to inhibit the production of the independent ventricular rhythm. 6. 6. Stimulation of the sympathetic when the vagus is paralyzed will induce the arrhythmia.

A new method for clinical determination of human capillary tension

Abstract 1. 1. Methods for the determination of human capillary pressure have been reviewed and criticism has been attempted from the viewpoints of accuracy and of clinical applicability. 2. 2. A device is described which is easily applicable to routine clinical use. The results obtained fall well within those obtained by the method of direct intubation of Landis, thus leading us to believe that they are substantially accurate. 3. 3. The average capillary pressure, in the normal individual we find to be 18–29 mm. Hg.