Proteinuria effect on toxicity of mercurial diuretics in the rat

Western partment

of Medicine,

Society for Clinical Research

University

of Utah

College of Medicine.) When it was decided to undertake a thorough study of copper metabolism and its relationship to hematopoiesis, it became apparent that a simplified method for the determination of copper in blood and its components is needed. Methods in current use require either ashing of the material prior to calorimetry, repeated extractions of the material with trichloracetic acid or extraction of the color complex with amyl alcohol; each method has certain objectionable features. A simple and accurate method for the determination of copper in small samples of plasma, whole blood, red blood cells and white blood cells is outlined. The proposed method is based on the principle used for the determination of serum iron, namely, the liberation of copper from its protein binding by the use of dilute HCI, followed by removal of the proteins with trichloracetic acid. This leaves the copper in the supernatant in such a form that it can be measured directly by the use of sodium diethyldithiocarbamate as color reagent. The method can be adapted to large or small volumes of material. With a Beckman spectrophotometer or similar instrument, determinations can be made on as little as 1.0 ml. of plasma, blood or cells, with an accuracy as great as reported for other procedures. Recovery of added copper ranged from 97 to 110 per cent. The procedure requires only forty to fifty minutes for completion. Various applications of this method to the study of copper metabolism will be discussed. CARDIAC EFFECTS OF DIHYDROERGOCORNINE.

D. IV. Leik, M.D. (by invitation) and Stephen R. Elek, M.D. Los Angeles, Calif. (From

the

University

Department of Southern

of

Cardiology

California

of Medicine.) /l;endkos’ studies in inverted patients with cardiac and general have indicated that this finding is sive sympathetic stimulation (tone)

School

T waves in anxiety states due to excesof the heart.

We were interested in studying the participation of the sympathetic nervous system in inverted T waves resulting

from myocardial

infarction

by

testing with the sympatholytic agent DHO-180. Five males in the third to fifth week convalescence from myocardial infarction and three with established angina who had inverted T waves were studied. In addition, two patients APRIL,

1950

539

with auricular fibrillation, one with supraventricular tachycardia and two with clinical hyperthyroidism, one of whom had electrocardiographic abnormalities due to hyperthyroidism, were tested. DHO-180 was given intravenously in doses of 0.5 to 1 mg. to fourteen patients resulting in a slight to moderate decrease in systolic and diastolic blood pressure and heart rate. One patient with hypertension and tachycardia showed the most marked lowering of both blood pressure and pulse. Only one of the five patients with myocardial infarction showed return of the inverted T waves in the chest leads toward normal. In one of the three patients with angina the inverted T waves became upright in two leads. In one patient with supraventricular tachycardia normal sinus rhythm occurred thirty minutes after injection. The auricular fibrillation in two patients was unchanged. In two young hyperthyroid patients DHO-180 produced an increase in amplitude of T waves in two leads in one, while in the more severe case control inverted T waves became upright. In the latter patient a more marked sympathetic activity is assumed to be the cause of the electrocardiographic abnormalities. Our observations indicate that the sympathetic nervous system probably does not participate in the inversion of T waves due to organic cardiac dGease but does influence the T wave abnormalities found in hyperthyroidism. PROTEINURIA EFFECT ON TOXICITY OF MERCURIAL DIURETICS IN THE RAT.

Lippman, M.D. the

Institute

Richard W. Los Angeles, Calif. (From

for Medical

Research,

Ce-

dars of Lebanon Hospital.) Rats were administered an intravenous dose of mercurial diuretic (mersalyl or meralluride sodium) varying from 0.26 to 1.95 mg Hg. The control animals received intraperitoneal injections of 0.85 per cent sodium chloride solution. At autopsy the kidneys of the control animals showed severe, acute, necrotizing nephrosis. The severity, and evidence of healing, was related to the dose and time interval until kill. Some of the animals died before the experiment was terminated at the end of one week. The experimental animals received intraperitoneal injections of bovine albumin in the dosage used by Addis to produce massive proteinuria. These animals receiving the mercurial after the onset of proteinuria were unaffected in

Western

540

Society for Clinical Research

the gross. Microscopic sections of the kidney revealed slight degrees of acute nephrosis. This effect was attributed to the inhibition of mercurial reabsorption when the tubules are saturated with protein. The experimental animals which received the mercurial before the onset of proteinuria were most severely affected. Most of the animals died before termination of the experiment at one week and the kidneys were subject to the most severe tubular destruction of acute, necrotizing nephrosis. This effect was attributed to the more rapid reabsorption of mercurial, concomitant with more rapid reabsorption of protein during the tubular loading phase.

LONG-TERM STUDY OF THE HYPOTENSIVE EFFECTSOF VERATRUM VIRIDE IN HYPERTENSIVE PATIENTS. J. D. McNair, M.D.

(by invitation) and George C. Gr@th, M.D. Los Angeles, Calif. (From the Department of

Cardiology,

University

of

Southern

California School of Medicine.) This study was carried out to determine if Veratrum viride is an effective agent for lowering blood pressure in a group of essential hypertensive patients. The drug used was vertavis, which is Veratrum viride (Irwin Neisler and Co.), standardized in craw units with 10 craw units to each tablet. The tablets used for placebo were made by the same company and were in every way similar to the tablets containing the drug. All of the patients were regular visitors to various clinics at this hospital and, therefore, have been carefully studied to determine the type of hypertension. The patients were unselected and originally comprised a group of twenty-eight essential hypertensives; however, one patient was dropped because the blood pressure was too low and five patients stopped attending the clinic before treatment was begun. The remaining twenty-two patients who comprised this study all had blood pressures above 175 mm. Hg systolic and 100 mm. Hg diastolic. The average age for the group was fifty-three years, the youngest being thirty-two and the oldest eighty-six. There were fourteen females and eight males, twelve white and ten Negro patients. The average duration of hypertension was nine years, the shortest six months and the longest thirty years. The period of study for each patient varied between two and five months. Fifty per cent of the patients claimed they were improved symptomatically, but there was

no correlation between change in blood pressure and symptomatic improvement. The average change in blood pressure while taking the drug was a drop of 7 mm. systolic and a drop of 6.6 diastolic pressure. The average pulse drop was 3 beats per minute. However, the normal variation of the blood pressure in the patient without treatment was far greater than the average change in blood pressure under treatment. Veratrum viride, given in the form of vertavis@ by mouth, had no significant effect on the blood pressure of twenty-two unselected hypertensive patients despite the fact that the drug was given to the point of tolerance in each patient.

RESONANT PHENOMENAOF THE AORTA AND SMALLERARTERIES.John P. Meehan, M.D.

(Introduced ty Dr. Douglas R. Drury). Los Angeles Calif. (From the University of Southern California.) The study of some of the resonant phenomena of the aorta has been approached by a direct experimental method. Free pressure oscillations were produced experimentally in the aorta of an intact animal. These oscillations were introduced into the aorta through a sound inserted in the left carotid artery and extending to the base of the aorta. Simultaneous pressure records were made from the base of the aorta, the femoral and the brachial arteries when feasible. The magnitude, frequency and velocity of transmission of the free oscillations to the smaller arteries were determined from the records. The experiments were performed on animals with normal arterial pressures as well as on animals made hypotensive by bleeding and hypertensive by the intravenous administration of adrenalin solutions. The frequency of the experimentally produced free pressure oscillations proved to be the same as those usually seen in the aorta following closure of the aortic valve. The frequency was only slightly increased in hypertensive and very much reduced in hypotensive The

transmission

to the

smaller

animals animals.

arteries

was

variable but usually better to the brachial artery. In markedly hypotensive animals the oscillations were not transmitted to the smaller arteries. The experiments were carried out on large rabbits, cats, dogs and small goats in an effort to determine if there were any fundamental differences in the various animals frequently used as experimental subjects. Only slight variations in the data were noted and AMERICAN

JOURNAL

OF

MEDICINE