Vasoactivity of azides in hypertension

Southern Society for Clinical Research NUCLEOTIDE LEVELS IN HUMAN CARDIAC MUSCLE. W. J. Burdette. * Chester Beatty Research Inst. of the Royal Cancer Hospital and the Brompton Hospital, London, England. Fresh, auricular muscle was obtained from eight patients at the time of cardiotomy for mitral stenosis and was placed on ice immediately. After weighing, the myocardium was homogenized and an acid extract prepared. Dowex-1 (200 to 400 mesh) was then used as a formate column to separate the nucleotides. The fractions were collected in volumes of 5 ml., the optical densities of which were read at 260 and 275 rnp in a Beckman model DU spectrophotometer. The results were rather uniform for the various specimens. The average amount (PM/ gm.) of AMP was 0.721, of ADP was 0.292, and of ATP was 0.138. Complete separation of other nucleotides was not accomplished but their presence suggests that the adenosine system may not solely be involved in energy exchanges during muscular contraction of the human heart. CASE OF COLLAGEN DISEASE (SCLERODERMA)IN WHICH PLEUROPNEUMONIA-LIKE ORGANISMS WERE ISOLATEDFROMAN OVARIAN CYST. S. W. Bush, L. B. Robinson, W. E. C. Wacker and T. M. Brown.* Dept. of Medicine, George Washington Univ. School of Medicine, and the Arthritis Research Unit, Medical Service, V. A. Hospital, Washington, D. C. The case is that of a twenty-nine year old woman with repeated genitourinary infections for five years treated with penicillin. The present illness began five months before hospitalization. Clinical and laboratory studies were compatible with disseminated lupus erythematosus but no L.E. cells were found. Recurrent Escherichia coli urinary infections were treated with antibiotics other than penicillin. Cortisone was employed intermittently for symptomatic control. Laparotomy disclosed a follicular ovarian cyst. The clear cystic fluid contained pleuropneumonialike organisms in pure culture. Improvement after surgery was followed by a downhill course. Treatment consisted of cardiac management and cortisone therapy. Autopsy, after fifteen months of illness, revealed findings compatible with scleroderma in the skin, gastrointestinal tract, lungs and heart. This is the first case in which pleuropneumonia-like organisms (L organisms) were obtained from an ovarian cyst. These findings are interesting in view of the long-standing speculaJULY,

1955

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tion regarding the role of pleuropneumonia-like disease, genitourinary organisms in Reiter’s infections, rheumatoid arthritis and rheumatic fever. Also, the findings may pertain to the known ability of penicillin to induce the formation of ‘L’ forms from common bacteria. No conclusions regarding the etiology of collagen diseases can be drawn from an isolated case but additional studies appear indicated. THE LEUKOPENIA OF VIRUS INFECTION-RELATION TO THE CONCENTRATIONOF VIRUS AND THE VIRAL LESION. G. R. Gary, W. B. Sorrel1 and E. D. Kilbourne.* Dept. of Medicine, Tulane Univ. School of Medicine, New Orleans, La. The well known leukopenia of virus infections is an enigmatic phenomenon which has received little study. With the belief that investigations on the genesis of this leukopenia might aid in elucidation of the pathogenesis of viral disease, a study was undertaken of experimental influenza virus infection. Adult male CFW mice weighing 20-22 gm. were inoculated intranasally with either lo6 EIDbo of influenza A virus (PR8 strain) or a control injection of saline. Both inocula contained penicillin and streptomycin. At varying intervals following infection (twelve, twenty-four, forty-eight, seventy-two and ninety-six hours) mice (four/group) were bled from the tail, then killed for study of pulmonary lesions, pulmonary virus concentrations and bone marrow cytology. A 22 per cent decrease in the total leukocyte counts of virus-infected mice was noted fortyseven to ninety-six hours after inoculation. Differential counts revealed an absolute lymphopenia representing a 40-45 per cent reduction in lymphocytes and a concomitant, absolute neutrophilia. Leukopenia occurred twenty-four hours subsequent to the logarithmic phase of viral increase, coincident with the attainment of maximal viral concentration, and twenty-four hours prior to the appearance of pneumonia. Thus infection of a murine host with influenza virus results in an absolute lymphopenia and an absolute neutrophilia temporally related to the peak of virus increase but prior to the appearance of the gross viral lesion. VASOACTIVITY OF AZIDES IN HYPERTENSION. P. Comens (introduced by H. A. Schroeder*). Hypertension Div., Dept. of Internal Medicine, Washington Univ. School of Medicine, St. Louis, MO. Utilizing photoelectric plethysmographs, photographic recordings were made in dogs after

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intraarterial injections of choline azide (0.4 mg./ kg.) and sodium azide (0.1 mg./kg.). Both produced unilateral local vasodilatation in the extremities of ten normotensive dogs, more marked with choline azide. A mean drop in diastolic pressure of 33 mm. Hg at fifteen minutes for both was more prolonged with the choline salt. Toxic doses of the latter (4.0 mg./ kg.) caused marked electrocardiographic abnormalities. Two unanesthetized renal hypertensive dogs with blood pressures of 250/l 50 and 300/160 mm. received ten daily oral doses of choline azide; mean diastolic pressures dropped 44 to 64 mm. Hg for as long as five hours with hours. When given recovery in twenty-four intravenously, both drugs caused negligible late depressor effects in anesthetized normotensive rats. However, some operated animals showed significant diastolic depression only with choline azide. This agent administered gastrically caused insignificant changes in normotensive but marked prolonged depression in hypertensive rats. Neither agent blocked the pressor action of nor-epinephrine in vim, although by the rabbit aorta strip method of Furchgott 0.05 mg. choline azide blocked the action of 2.0 y norepinephrine. Sodium azide (5.0 mg.) used for long periods in four hypertensive patients at four-hourly intervals caused little or no effect upon blood pressure. These results suggest that choline azide is a long acting vasodilator when given orally to rats and dogs. EFFECT OF L-TRIIODOTHYRONINE ON PROTEIN SYNTHESISRATE MEASURED WITH N15 GLYCINE IN PATIENTS WITH PRIMARY MYXEDEMA. K. R. Crisjxll, * W. Parson* and G. F. Hollz$ield. Dept. of Internal Medicine, Univ. of Virginia School of Medicine, Charlottesville, Va. The amino acid pool and the protein synthesis rate has been determined in five patients with primary myxedema using isotopic nitrogen, Nr5. The patients were studied under the usual metabolic regimen. An interesting but unexplained finding was a moderate degree of positive nitrogen balance as determined by classic nitrogen studies. However, the protein synthesis rate as determined by the isotopic technic was consistently decreased in patients with myxedema. The average in the five patients was 379 mg./kg. per twenty-four hours (range 180-490) as compared with an average of 756 mg./kg. per twenty-four hours in five healthy

volunteers (range 610-970). The size of the amino acid pool was not consistently altered. Studies will be presented which show that several days after first administering L-triiodothyronine there is no increase in the protein synthesis rate. However, after administering the L-triiodothyronine for six to nine months the protein synthesis rate was markedly increased. For example, in one patient there was an increase in protein synthesis rate from 350 mg./kg. per twenty-four hours to a high of 1,300 mg./kg. per twenty-four hours. HYPERACTIVITY OF THE BLOOD COAGULABILITY CONTROL MECHANISM-A POSSIBLE CAUSE OF IRREVERSIBLESHOCK. J. W. Crowell and W. L. Read (introduced by A. C. Guyton”). Dept. of Physiology and Biophysics, School of Medicine, Univ. of Mississippi, University, Miss. If an animal is bled until his arterial pressure is very low and this pressure level is maintained for a long period of time, a slowly falling blood pressure develops which continues to fall although the withdrawn blood is reinjected. Transfusion of additional blood or injection of sympathomimetic drugs has only a temporary effect, for the animal eventually dies. This is a type of irreversible shock. Experiments in our laboratory have shown that concurrent with the fall in arterial pressure there is also a fall in the coagulation time of the circulating blood and that this hypercoagulability predisposes to the formation of large numbers of very small blood clots. If hypotension continues long enough for a major portion of the lung capillaries to be blocked, then the pulmonary resistance becomes so great that adequate circulation cannot be maintained. By use bf large doses of heparin given before the beginning of the period of hypotension, the mortality rate from the hemorrhagic shock experiment is greatly lessened. Only one of ten dogs given heparin developed irreversible shock as compared with nine of ten dogs given no heparin. CLINICAL RESULTSWITH PENTOLINIUMIN TREATMENT OF HYPERTENSION; COMPARISON WITH HEXAMETHONIUM WHEN BOTH ARE USED IN COMBINATION WITH RAUWOLFIA. E. Dennis, R. Ford, W. Hughes, R. Hershberger and J. H. Moyer.* Baylor Univ. College of Medicine, Houston, Tex. Recent reports by Freis and his co-workers have indicated that pentolinium is superior to other anti-hypertensive agents. In order to AMERICAN

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