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The influence of certain sulfhydryl compounds on the toxicity of an organic mercurial diuretic
Piron,
A.: 1946.
The
Cardiopaithy
SELECTED
ABSTRACTS
of Friedreich’s
Disease.
155 Acta.
cardiol.
1:305
(No.
3 & 4),
A detailed study of the cardiovascular system was made in two brothers with Friedreich disease. Both patients appeared to have an angina1 syndrome and showed electrocardiographic The author points out that cardiac changes consistent with a diagnosis of coronary insufficiency. disorders occurring in the course of Fciedreich’s disease may reasonably be attributed to the effect He concludes that the hypothesis of the of the medullary lesions on the coronary circulation. medullary origin of angina pectoris is supported by the clinical evidence found in cases of thii type. LAPLAC’I’..
Frimann-Dahl,
J. : On
Venography
of the
Lower
Extremities.
Acta
radiol.
28:199,
1947.
The author discusses the pertinent information derived from venography in the diagnosis of acute and chronic deep thrombophlebitis of the lower extremities, and adviises a number of modifications in the technique in order to avoid certain pitfalls in the interpretation of the films. He calls attention to the finding that if the patient lies in the supine position, with the leg supported on the calf and heel, there will be a defective filling of the deep veins in the muscular pad of the calf with the result that the film may resemble the picture seen in thrombosis of the deep veins in this area. He therefore advocates that all pressure be removed from the calf while the contrast medium is being injected, and also that lateral films should be taken to decide whether an involved vein is superficial or deep. On the basis of the findings with venography, the author concludes that pressure against the calf veins during rest in bed partly or completely interferes with the return of blood through this system of vessels, and that this mechanism may play an important role in the development of venous thrombosis. Since crossing the legs in bed likewise interferes with filling of the calf veins with the contrast medmm, it 1s possrble that thus posrtron may also rontrrbute to venous thrombosis. ARRAMSON. Long,
W. K., and Farah, A.: The Influence of Certain Sulfhydryl Toxicity of an Organic Mercurial Diuretic. J. Pharmacol. (Dec.), 1946.
Compounds & Exper. Therap.
on the 88:388
Forty deaths following the use of mercurial diuretics have been reported. Experimental study has suggested that the cause of death is due to a toxic action of mercury on the heart, with resultant ventricular fibrillation, or to respiratory failure secondary to a fall in blood pressure. This study evaluates the effect of substances containing the sulfhydryl group on the cardiac toxicity of salyrgan. 2,3 dimercaptopropanol (BAL), cysteine hydrochloride, glutathione, methionine, and cystine were tested. Three types of experimental conditions were evaluated. Salyrgan was used as the mercurial in each. (1) Mice were given varying amounts of salyrgan and the 50 per cent lethal dose (L.D.50) determined. The sulfhydryl compounds were then injected into mice and followed in one minute by the calculated L.D.50. The protective action of the sulfhydryl compounds was measured by the increasing amount of salyrgan necessary to produce a 50 per cent mortality. (2) Action of salyrgan, protected and unprotected, on the circulation of dogs was determined by simultaneous measurement of blood pressure, venous pressure, heart rate, and electrocardiogram. (3) Action on the heart-lung preparation of Starling was determined by simultaneous measurement of arterial pressure, pulmonary artery pressure, and left and right auricular pressures. Methionine and cystine were ineffectual in protecting mice against the control L.D.50 of sal.yrgan. No improvement in circulatory function was noted. BAL, cysteine hydrochloride, and glutathione increased the L.D.50 of salyrgan in mice. Their administration promptly reversed salyrgan-induced heart failure in dogs. The most severe toxic manifestations short of ventricular fibrillation could be reversed. Once ventricular fibrillation had begun, these substances were ineffectual. In the heart-lung preparation, the protective action of BAL, cysteine hydrochloride,
156
AMERICAN
HEART
JOURNA
1.
and glutathione was about equal when calculated in t’erms of sulfhydryl equivalents. In the intact dog, BAL was five to eight times as effective as cysteine hydrochloride and glutathione. None had any effect on spontaneous or sodium pentobarbital-induced cardiac failure in the heart-lung preparation.
Andre,
M. J. : A New Case of a Fatal of Asthma. Acta clin. belg. 2:l
Attack ofAsthma. (Jan.-Feb.), 1947.
The
Circulatory
Manifestations
The author reports the case of a 16-year-old girl who died suddenly in the third attack of asthma which had occurred in the space of twelve days. The patient was studied carefully with special reference to the associated disturbance of cardiovascular function. It is pointed out that the predominant lesion in fatal asthma is acute pulmonary emphysema due to bronchial and bronchiolar block by abnormal glandular secretion. Although death is attributed to anoxia, it is impossible to evaluate the element of circulatory impairment, manifestations of which include cutaneous vasoconstriction, tachycardia, weak pulse, and hypotension. The most characteristic sign is Kussmaul’s pulse: weakening or disappearance of the pulse during inspiration. The mechanism of this paradoxical pulse is discussed in detail. LAFIACR. Raber,
M. D., and Daley, J. Obst. & Gynaec. Brit.
D.: Emp.
Coarctation 46:91 (Feb.),
of Aorta 1947.
in
Association
With
Pregnancy.
The literature on the titled subject is reviewed and the description of another case is added. ‘1’0 date, forty-three cases have been reported in which the majority successfully carried through pregnancy. From thes: reports, it is clear that pregnancy is not contraindicated in the majority of these patients. The authors recommend adequate spacing of pregnancy and the avoidance of late childbearing as a wise precaution. In spite of reassuring results indicating safety of vaginal delivery, the authors have felt inclined “to play safe, ” and favored delivery by cesar.an section of their 26.year-old primipara. WAGNER.
The Respiratory and Circulatory Response of Dripps, R. D., and Comroe, J. II., Jr.: Normal Man to Inhalation of 7.6 and 10.4 Per Cent CO2 With a Comparison of the Maximal Ventilation Produced by Severe Muscular Exercise, Inhalation of CO2 and Maximal Voluntary Hyperventilation. Am. J. Physiol. 149:43 (April), 1947. In these experiments, the effects produced by breathing high concentrations (7.5 to 10 per cent) of carbon dioxide have been measured in a large number of normal subjects. In addition the maximal respiratory minute volume produced by inhalation of 7.6 and 10.4 per cent carbon dioxide was compared with that resulting from exhausting muscular exercise and maximal voluntary hyperventilation. When 7.6 per cent carbon dioxide in oxygen was inhaled, the average minute volume of respiration increased to 51.5 liters per minute, pulse rate increased 16.7 beats per minute, and the blood pressure rose 30.8 mm.Hg systolic and 22.2 mm.Hg diastolic. With 10.4 per cent carbon dioxide in oxygen, the respiratory minute volume was 76.3 liters, pulse rate increased 15.6 per When minute, and the blood pressure rose 33.4 mm.Hg systolic and 25.0 mm.Hg diastolic. carbon dioxide inhalation was stopped, diastolic pressure fell abruptly to normal; the respiration and systolic pressure returned slowly to normal. The symptoms noted with carbon dioxide inhalations were, in the order of frequency, headache, dizziness, and dyspnea. Most of the dizziness was noted in the immediate postinhalation period, the same time as the abrupt fall in diastolic pressure occurred. The observed effect of carbon dioxide, is the sum of a direct carbon dioxide stimulation of medullary centers and a narThey conclude that carbon dioxide inhalation cotic action which depressed the respiratory center. in the treatment of indivuduals with depressed centers (due to anesthesia, morphine, and SO forth) may produce further narcosis with or without hyperpnea or hypertension. They recommend a mechanical increase of ventilation if such is desired.
A.: 1946.
The
Cardiopaithy
SELECTED
ABSTRACTS
of Friedreich’s
Disease.
155 Acta.
cardiol.
1:305
(No.
3 & 4),
A detailed study of the cardiovascular system was made in two brothers with Friedreich disease. Both patients appeared to have an angina1 syndrome and showed electrocardiographic The author points out that cardiac changes consistent with a diagnosis of coronary insufficiency. disorders occurring in the course of Fciedreich’s disease may reasonably be attributed to the effect He concludes that the hypothesis of the of the medullary lesions on the coronary circulation. medullary origin of angina pectoris is supported by the clinical evidence found in cases of thii type. LAPLAC’I’..
Frimann-Dahl,
J. : On
Venography
of the
Lower
Extremities.
Acta
radiol.
28:199,
1947.
The author discusses the pertinent information derived from venography in the diagnosis of acute and chronic deep thrombophlebitis of the lower extremities, and adviises a number of modifications in the technique in order to avoid certain pitfalls in the interpretation of the films. He calls attention to the finding that if the patient lies in the supine position, with the leg supported on the calf and heel, there will be a defective filling of the deep veins in the muscular pad of the calf with the result that the film may resemble the picture seen in thrombosis of the deep veins in this area. He therefore advocates that all pressure be removed from the calf while the contrast medium is being injected, and also that lateral films should be taken to decide whether an involved vein is superficial or deep. On the basis of the findings with venography, the author concludes that pressure against the calf veins during rest in bed partly or completely interferes with the return of blood through this system of vessels, and that this mechanism may play an important role in the development of venous thrombosis. Since crossing the legs in bed likewise interferes with filling of the calf veins with the contrast medmm, it 1s possrble that thus posrtron may also rontrrbute to venous thrombosis. ARRAMSON. Long,
W. K., and Farah, A.: The Influence of Certain Sulfhydryl Toxicity of an Organic Mercurial Diuretic. J. Pharmacol. (Dec.), 1946.
Compounds & Exper. Therap.
on the 88:388
Forty deaths following the use of mercurial diuretics have been reported. Experimental study has suggested that the cause of death is due to a toxic action of mercury on the heart, with resultant ventricular fibrillation, or to respiratory failure secondary to a fall in blood pressure. This study evaluates the effect of substances containing the sulfhydryl group on the cardiac toxicity of salyrgan. 2,3 dimercaptopropanol (BAL), cysteine hydrochloride, glutathione, methionine, and cystine were tested. Three types of experimental conditions were evaluated. Salyrgan was used as the mercurial in each. (1) Mice were given varying amounts of salyrgan and the 50 per cent lethal dose (L.D.50) determined. The sulfhydryl compounds were then injected into mice and followed in one minute by the calculated L.D.50. The protective action of the sulfhydryl compounds was measured by the increasing amount of salyrgan necessary to produce a 50 per cent mortality. (2) Action of salyrgan, protected and unprotected, on the circulation of dogs was determined by simultaneous measurement of blood pressure, venous pressure, heart rate, and electrocardiogram. (3) Action on the heart-lung preparation of Starling was determined by simultaneous measurement of arterial pressure, pulmonary artery pressure, and left and right auricular pressures. Methionine and cystine were ineffectual in protecting mice against the control L.D.50 of sal.yrgan. No improvement in circulatory function was noted. BAL, cysteine hydrochloride, and glutathione increased the L.D.50 of salyrgan in mice. Their administration promptly reversed salyrgan-induced heart failure in dogs. The most severe toxic manifestations short of ventricular fibrillation could be reversed. Once ventricular fibrillation had begun, these substances were ineffectual. In the heart-lung preparation, the protective action of BAL, cysteine hydrochloride,
156
AMERICAN
HEART
JOURNA
1.
and glutathione was about equal when calculated in t’erms of sulfhydryl equivalents. In the intact dog, BAL was five to eight times as effective as cysteine hydrochloride and glutathione. None had any effect on spontaneous or sodium pentobarbital-induced cardiac failure in the heart-lung preparation.
Andre,
M. J. : A New Case of a Fatal of Asthma. Acta clin. belg. 2:l
Attack ofAsthma. (Jan.-Feb.), 1947.
The
Circulatory
Manifestations
The author reports the case of a 16-year-old girl who died suddenly in the third attack of asthma which had occurred in the space of twelve days. The patient was studied carefully with special reference to the associated disturbance of cardiovascular function. It is pointed out that the predominant lesion in fatal asthma is acute pulmonary emphysema due to bronchial and bronchiolar block by abnormal glandular secretion. Although death is attributed to anoxia, it is impossible to evaluate the element of circulatory impairment, manifestations of which include cutaneous vasoconstriction, tachycardia, weak pulse, and hypotension. The most characteristic sign is Kussmaul’s pulse: weakening or disappearance of the pulse during inspiration. The mechanism of this paradoxical pulse is discussed in detail. LAFIACR. Raber,
M. D., and Daley, J. Obst. & Gynaec. Brit.
D.: Emp.
Coarctation 46:91 (Feb.),
of Aorta 1947.
in
Association
With
Pregnancy.
The literature on the titled subject is reviewed and the description of another case is added. ‘1’0 date, forty-three cases have been reported in which the majority successfully carried through pregnancy. From thes: reports, it is clear that pregnancy is not contraindicated in the majority of these patients. The authors recommend adequate spacing of pregnancy and the avoidance of late childbearing as a wise precaution. In spite of reassuring results indicating safety of vaginal delivery, the authors have felt inclined “to play safe, ” and favored delivery by cesar.an section of their 26.year-old primipara. WAGNER.
The Respiratory and Circulatory Response of Dripps, R. D., and Comroe, J. II., Jr.: Normal Man to Inhalation of 7.6 and 10.4 Per Cent CO2 With a Comparison of the Maximal Ventilation Produced by Severe Muscular Exercise, Inhalation of CO2 and Maximal Voluntary Hyperventilation. Am. J. Physiol. 149:43 (April), 1947. In these experiments, the effects produced by breathing high concentrations (7.5 to 10 per cent) of carbon dioxide have been measured in a large number of normal subjects. In addition the maximal respiratory minute volume produced by inhalation of 7.6 and 10.4 per cent carbon dioxide was compared with that resulting from exhausting muscular exercise and maximal voluntary hyperventilation. When 7.6 per cent carbon dioxide in oxygen was inhaled, the average minute volume of respiration increased to 51.5 liters per minute, pulse rate increased 16.7 beats per minute, and the blood pressure rose 30.8 mm.Hg systolic and 22.2 mm.Hg diastolic. With 10.4 per cent carbon dioxide in oxygen, the respiratory minute volume was 76.3 liters, pulse rate increased 15.6 per When minute, and the blood pressure rose 33.4 mm.Hg systolic and 25.0 mm.Hg diastolic. carbon dioxide inhalation was stopped, diastolic pressure fell abruptly to normal; the respiration and systolic pressure returned slowly to normal. The symptoms noted with carbon dioxide inhalations were, in the order of frequency, headache, dizziness, and dyspnea. Most of the dizziness was noted in the immediate postinhalation period, the same time as the abrupt fall in diastolic pressure occurred. The observed effect of carbon dioxide, is the sum of a direct carbon dioxide stimulation of medullary centers and a narThey conclude that carbon dioxide inhalation cotic action which depressed the respiratory center. in the treatment of indivuduals with depressed centers (due to anesthesia, morphine, and SO forth) may produce further narcosis with or without hyperpnea or hypertension. They recommend a mechanical increase of ventilation if such is desired.