Observations concerning the rise and fall of free and esterified cholesterol in rats made hypercholesteremic by a new method

Western Society for Clinical Research

394

Whereas gastrointestinal symptoms were the commonest initial evidence of toxicity, they accompanied tinnitus, deafness, scotomas and hypotension when the latter were present. The quinidin content of the plasma of twelve patients at the time of conversion of auricular fibrillation to sinus rhythm varied from 7.48 to 23.7 mg. per L. in six instances of rheumatic heart disease (including three conversions of the same patient at 10.8, 11.7 and 14) and 3.30 to 5.67 in six patients with coronary arteriosclerosis with or without hypertension. Two patients had not converted at the time quinidin therapy was stopped because of significant hypotension. QUANTITATIVE

STUDY OF QUINIDINE THER-

Maurice Sokolow, M.D. and (by invitation) Archie L. Edgar, M.D., San Francisco, California. (From the University APY.

of California

Medical

School.)

The quantitative aspects of quinidine therapy were investigated by determining multiple blood and urine quinidine levels in forty-one patients on varying dose schedules. The photofluormetric method of Brodie, as modified by Lilienthal, was used. Sinus rhythm was re-established in thirteen of fifteen cases of auricular fibrillation or flutter. The amount of quinidine required for conversion, using the two or four-hour schedule, varied from 1.2 Gm. in twenty hours to 9.3 Gm. in ninety-six hours, with maximum blood levels of 2.0 to 13.7 mg./L. and an average of 7.0 mg./L. In only two cases was the level required for conversion less than 4 mg./L. In one case converted with a level of 7 mg./L. relapse occurred on maintenance doses with a level of 3.8 mg./L.; reconversion resulted when a level of 5.5 mg./L. was obtained with higher doses. In the two failures levels of 10 and 11 mg./L. were attained. In one case of ventricular tachycardia approximately 4 mg./L. was found to be the critical blood level preventing recurrent attacks. Four relapses occurred when the level was 3.3, 3.5, 3.3 and 2.5 mg./L. Sinus rhythm was reestablished at levels of 4.1, 4.3, 5.6 and 4.6 mg./L. The average net peak level (subtracting the morning residual level resulting from the previous day’s therapy) obtained with 0.2 Gm. every two hours for five doses was 3.9 mg./L.; for 0.4 Gm. every two hours for five doses, 4.9 mg./L.; for 0.6 Gm. every two hours for five doses, 5.5 mg./L. When fixed daily doses were given every

four or six hours, a plateau was reached within seventy-two hours; it lasted three to four days and was followed by a gradual decline. The increment in blood level from single added doses was found to be 0.8 mg./L. with 0.2 Gm.; 1.2 mg./L. with 0.4 Gm. and 1.9 mg./L. with 0.6 Gm. The increment progressively decreased after the first two or three doses when the same dose was given every two hours. Comparable blood levels were reached in six observations when oral and intramuscular quinidine were given to the same patient. An average of 49 per cent of the last evening level was still present in the blood approximately twelve hours later. Urinary excretion accounted for only 10 to 20 per cent of the total daily dose. Measurable blood levels were found as long as seventy-two hours and urine levels as long as forty-eight hours after quinidine was discontinued. TAP WATER

SODIUM IN A

Low SALT DIET.

Seymour L. Cole, M.D. (by invitation and introduced by Edward Tyler, M.D.), Los Angeles, California. Drinking water has frequently been overlooked as a source of sodium large enough to be considered when restricting that element in the solid part of the diet to 0.5 to 1.0 Gm. day. Analyses of the tap water of the Los Angeles County General Hospital show it to contain 25 to 30 mg. sodium per 100 cc. The factors responsible are the high salt content of the original source, the Colorado River, and addition of salt in the Metropolitan Water District and in the hospital itself for softening purposes. Study of the low salt diets of Schemm, Schroeder and others reveals them to allow 1,000 to 2,500 cc. and more of drinking water per day. In addition there are 500 to 600 cc. of hidden water used in the cooking of rice and preparation of leafy vegetables. Thus, an intake of 3,000 cc. of drinking water containing 30 mg. of sodium per 100 cc. in itself would provide 900 mg. of the allowed 1,000 mg. of sodium. Therefore, to attain a low salt diet distilled water or low sodium content water should be substituted for tap water of high sodium content in addition to other precautionary measures. OBSERVATIONS CONCERNING THE RISE AND FALL OF FREE AND ESTERIFIED CHOLESTEROL IN RATS MADE HYPERCHOLESTEREMIC BY A NEW METHOD. Meyer AMERICAN

JOURNAL

OF

MEDICINE

Western

Society

for Clinical

Friedman, M.D. and (by invitation) S. 0. Byers, Ph.D., San Francisco, California. (From

the

Cardiovascular

Harold

Brunn

Research,

Institute Mount

for Zion

Hospital.) 1 t was found possible to increase immediately the total cholesterol content of the rat’s plasma approximately 600 per cent above the normal level by the intravenous injection of a new preparation of free cholesterol. Immediately following such injections into 122 rats (30 mg. of cholesterol per 100 Gm. of body weight), the plasma free cholesterol content rose from a preinjection level of 12 to 295 mg. per 100 cc. However, no immediate rise occurred in the plasma esterified cholesterol. Three hours after the injection the free cholesterol fell to a value of 122 mg. per 100 cc. where it remained for approximately twelve hours. At this same time, however, the esterified cholesterol content of the rat’s plasma rose to a value approximately twice that of the preinjection level and it remained at this increased concentration for over twenty-four hours. At the end of thirty-six hours both the free and esterified cholesterol content of the rat’s plasma had returned to pre-injection levels. By means of this new technic the rate of disappearance as well as the partial esterification of injected free cholesterol was studied in a quantitative fashion.

EFFECT OF ENVIRONMENTAL TEMPERATURE ON THE FEBRILE REACTION TO TYPHOID PARATYPHOID VACCINES AND OTHER PYROGENS. R. Grant, Ph.D. (by invitation),

Marilyn Robbins, A.B., (by invitation) and I’. E. Hall, M.D., Palo Alto, California. The febrile response to intravenous injection of pyrogens in rabbits includes inhibition of the mechanisms for heat dissipation (polypnea and cutaneous vasodilatation) and moderate increase of heat production. Oxygen production is maximal about twenty minutes after injection, and the increase is about 15 per cent of the control value for the first hour. This metabolic response is uniform at enviromental temperatures from 31”~. to -5”~. and in completely shorn animals at -5”~. although control levels of oxygen consumption are about 110 per cent higher than normal under the last conditions. During the second and subsequent hours of fever MARCH,

f

949

Research

39.5

at moderate and high enviromental temperatures oxygen consumption usually remains slightly increased, but in animals exposed to severe cold oxygen usage shows sharp reduction below control values during the second hour associated with shivering. Recovery to normal or supranormal values follows during the third hour. In consequence of this inhibition of cold defense profound hypothermia develops following initial slight fever. At normal temperatures the second hour is marked by reduced inhibition of heat defense mechanisms or partial defervescence, and the third hour by renewed febrogenesis. Similar effects are obtained with an endogenous pyrogen (“Pyrexin”). ACUTE CORONARY ARTERY OCCLUSION AsSOCIATEDWITH EARLY ELECTROCARDIOGRAPHIC FINDINGS SUGGESTIVE OF PREDOMINANTLY SUBENDOCARDIAL INJURY. A “NEW” PATTERN OF MYOCARDIAL INFARCTION. Hans H. Hecht, M.D. and (by

invitation) Leonard W. Ritzmann, M.D. Salt Lake City, Utah. (From the Department of Medicine, University College of Medicine.)

of Utah

It is assumed that predominantly subepicardial lesions of the heart muscle are characterized ‘by electrocardiograms which display inversion of T and elevation of the RT segment in leads dominated by the effects of epicardial regions. In these leads subendocardial injury is suggested by upright T waves and by depression of the RT segment. As the exploring electrode of a unipolar system is primarily influenced by the electrical changes of adjacent tissues and to a much lesser degree by alterations in the electrical state of remote regions, subendocardial lesions must be more extensive than subepicardial involvement if changes of equal magnitude are to be recorded by an epicardial electrode. This is demonstrated in human subjects when pressure injury by a venous catheter exerted over a region of a few mm. may cause a monophasic deformation of the endocardial electrocardiogram but which leaves a simultaneously recorded electrocardiogram of the subjacent epicardial surface unaltered. These considerations are supported by observations on four patients, all with angina pectoris of many years’ duration, who entered the hospital with the typical signs and symp-