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Reflections on the use of propranolol in angina pectoris
light enough to be carried by a nurse, and it eliminates dependence on the power line and the necessity to run a ground wire. It is obvious that electrocardiograms taken by the electrodes-triangle are not substitutes for the usual U-lead ECG’s but the instrument’s purpose is to obtain prompt recording, diagnosis, and treatment of arrhythmias. As mentioned above, the electrodes-triangle is usually placed on the chest wall, so that it avoids interference of myograms due to any muscle motion or twitching by the patient. Consequently, a stable ECG is obtained in patients with tremor of the !iands, convulsion, dyspnea, and even orthopnea. By attaching it to a battery-powered portable electrocardiograph, it also has less interference by alternating current. When the electrodes-triangle is ulaced on the chest wall it may express atria1 activity much more than the usual electrocardiographic leads. Therefore. P waves and other atria1 oscillations such as fibrillation or flutter waves become more prominent even in a case when they are obscured in conventional leads. Prompt recognition of many types of arrhythmias is easy by this method. It is, however, not suitable for fine differentiation between atria1 and A-V nodal arrhythmias. In a diagnosis of this type of arrhythmia, it is important to know whether the P waves in Leads II, III, aVF, and aVs in 3 conventional way are upright or inverted. But we
Reflections
on the
Medical and surgical efforts m the treatment 01 angina pectoris due to ischemic heart disease have been mainly directed toward attempts at increasing myocardial blood supply. On one hand, we have seen the introduction and widespread use of a large number of short- or long-acting nitrate preparations, while on the other, our surgical colleagues have devised ingenious methods to promote myocardial revascularization from extracardiac sources. In both instances, their beneficial effects remain the subject of debate and controversy. This is not surprising. Angina pectoris is the subjective manifestation of a disease and is difficult to evaluate obiectivelv. Its natural history is quite variable, and even minor environmental factors can influence results in shortterm clinical trials. Drug evaluations in angina pectoris usually vary in design and often do not assess the stability of the disease during the study. In addition, the exact pathophysiology of angina is poorly understood. While occlusive coronary artery disease is the single most important ana-
cannot judge it from only- one electrocardiogram obtained by this method. This method is useful also in calculating a pulse deficit in rapid atria1 fibrillation, even by a busy nurse at night. In addition, the electrodes-triangle can be used with an electric defibrillator. By connecting the electrodes-triangle to the leads of an electric defibrillator, considerable time is saved in obtaining a prompt diagnosis and treatment of ventricular fibrillation in ward patients for emergency. It has to be emphasized that the electrodestriangle should not be placed close to the chest electrodes for electric discharge in order to prevent a burn at the site of the small eiectrodes by an electric discharge. For an emergency in a ward, the patient-leads of the electric defibrillator always should be connected to the terminals of the electrodes-triangle for ready use. Makoto Tukagi, M.D.
Susumzt Iclzinose, M.D. The Cardiology Bran& Lkfiartment
of Medicine
Kyoto City Hospital Kyoto, Japan REFEREL’CE 1. Green, H. instrument arrhythmias,
roprano
5.: The electrocardiophone: A newfor rapid bedside diagnosis of cardiac Circulation 36:975, 1967.
ect
tomical factor in :is etiology-, other factors may- ‘2 equally important. For example, the oxygen-wasting effect of excessive sympathetic stimulation, with its resulting positive chronotropic and inotropic effects, is well recognized and its deleterious effect in angina is well documented. The recent development of drugs capable of selectively biocking beta-sympathetic receptor sites has provided us with a new approach to the treatment of angina pectoris and has introduced a new pharmacologic tool in the investigation of cardiac function in health and disease. The vast majority of published reports indicate that in well-controlled, short-term clinical trials, propranolol, when given in adequate doses, is effective in reducing the frequency and severity of angina1 attacks and improves exercise tolerance. Indeed, preliminary reports also suggest that in patients with very advanced coronary -artery disease and severe angina, propranolol may influence the natural historv of this disease. Having administered propranolol to such patients, Wlolfson,
Volume Mwmber
80 3
Amsterdam, and Gorlini have reported data suggesting that the incidence of sudden death and acute myocardial infarction seems to be reduced, compared to similar groups receiving more traditional therapy or subjected to internal mammary artery implants. in our own clinic, propranolol is reserved for patients with very severe and intractable angina. Having treated in excess of 150 patients, for periods ranging from 6 months to 3 years, we have been impressed with the relatively low incidence of sudden death and myocardial infarction in a group with such severe disease. Also, in a preliminary trial of propranolol in acute coronary insufficiency, we have administered this drug to 15 patients admitted to the hospital with this syndrome. In all, angina1 symptoms had remained intractable in spite of the usual measures of bed rest, sedation, nitrates, heparin, and digitalis. In 13 of the 15 patients, symptoms subsided immediately. After an average follow-up period of 65 weeks, the course of the disease seems to have stabilized, as none of the 13 patients who initially responded to propranolol developed further episodes of acute coronary insufficiency or acute myocardial infarction. One subject died suddenly, after being free of angina for 67 weeks. The exact mechanism whereby propranolol is effective in angina is uncertain. Its administration is followed by many important hemodynamic changes, resulting both in an increase or a decrease in myocardial oxygen requirements. The bradycardia, the decrease in mean aortic pressure during exercise, the decrease in the rate at which pressure is developed by the ventricle, and the drop in cardiac output all result in decreased myocardial work and oxygen requirement. On the other hand, increased ventricular dimensions during exercise and the relative prolongation of systolic ejection period at rest and exercise tend to augment myocardial work and oxygen demand. In most cases, the net effect is a reduction in myocardial oxygen consumption estimated to be of the order of 25 per cent2 Thus, by blocking myocardial betaadrenergic receptors, propranolol appears to attenuate or prevent the increase in myocardial oxygen requirements resulting from the sympathetic stimulation taking place during exercise or emotional stress. Theoretically, propranolol should produce overall coronary vasoconstriction as cardiac work is reduced. Yet, there is some evidence that in subjects with coronary artery disease, beta-adrenergic blockade may suppress the initial coronary vasoconstriction during spontaneous angina1 attack? or after injection of catecholamines.3 It would be tempting to speculate that in coronary artery disease, it could effect a redistribution of myocardial blood flow favoring the ischemic areas. Propranolol’s quinidine-like action has been stressed. It antiarrhythmic properties may be of some benefit to patients whose angina1 attacks are associated with paroxysmal arrhythmias. Propranolol is a new and exciting addition to our therapeutic armamentarium, and is rapidly gaining favor in the treatment of a variety of cardiac disorders. As its use becomes more widespread, several
9nnotations
429
important considerations must be stressed in assessing its merits in the treatment of angina pectoris. These considerations pertain to the variability in dosage re’quired to produce a response in a group of patients, to potential hazards related to its use, and to adverse effects. It is evident that some patients with angina pectoris do not benefit from propranolol. This lack of response is not related to gastrointestinal absorption, Despite careful comparisons between responders and nonresponders, the phenomenon remains obscure, unexplained, and is unpredictable, so that therapeutic trial becomes necessary. It is also important to recognize that although the average effective daily dose is of the order of 240 mg., it may vary from 60 to 400 mg. Some patients have improvement at a lower dose; in others, significant additional benefit is frequently observed at higher dose levels.4 Thus, controlled clinical trials on a fixed dose may be difficult to evaluate and may, indeed, underestimate the properties of the drug. Beta-adrenergic blockade may, theoretically, induce bronchospasm. Although this has not been a problem in patients with a normal tracheobronchial tree, propranolol should be avoided in patients with a history of asthma and bronchospastic disease. Since propranolol increases atrioventricular conduction time and, by blocking adrenergic receptors, has a pronounced negative chronotropic effect, it is also contraindicated in patients with pre-existing sinus bradycardia or atrioventricular block. The most serious hazard peculiar to the use of propranolol is related to its negative inotropic effect. The sick heart depends on sympathetic tone, and beta-adrenergic blockade may precipitate overt congestive heart failure in patients with borderline compensation. In #our clinic, propranolol is reserved for patients with severe coronary artery disease and intractable angina, in whom pre-existing cardiac reserve is sometimes difficult to assess clinically. Since the positive inotropic effect of digitalis is not reversed by the beta-adrenergic blockade, we prefer to administer digitalis prior to giving propranolol. Failure to do so may, in part, explain the worsening symptoms of angina encountered in some published clinical trials6 In a few patients treated over a long time, we have observed a gradual exacerbation of angina1 symptoms after an initially good response. In several of thlese, the angina was frequently nocturnal. Although tolerance to the beneficial effects of the drug was suspected at first, careful examination indicated fluid retention, and administration of diuretics was promptly followed by amelioration of symptoms. Such patients often require the regular use of diuretic agents, Its use must be avoided in patients with overt congestive heart failure. Its negative inotropic effect also contraindicates its use in patients with mechanical impediments to cardiac function, such as valvular aortic stenosis, significant mitral insufficiency and ventricular dyskinesias, or aneurysms. What happens when a patient receiving propranolo1 develops an acute myocardial infarction? Is propranolol’s myocardial depressant effect a hazard? Does it predispose to intractable cardiogenic shock,
heart block, or asystole? These are important questions which, although not fully answerable at present, merit consideration. Some of our subjects have suffered acute myocardial infarction after an initial beneficial response. Except for sinus bradycardia during the first 24 hours, most have recovered without further complication. However, others have died suddenly and yet others have suffered cardiac arrest while in the hospital with intractable asystole or ventricular fibrillation. In the latter group of patients, severe and very advanced coronary artery disease was demonstrated post mortem. -1lthough we can speculate about the role played by propranolol in their deaths, failure to resuscitate them was probably related to the advanced stage of their disease. Several reports on the use of propranolo1 in acute myocardial infarction have appeared. Intractable shock or asystole did not seem to pose a special problem in these studies. Beta-adrenergic blocking agents inhibit the effect of catecholamines on the myocardium, probably by competitive antagonism at the receptor site. This inhibition can be overcome by sufficiently high concentrations of isoproterenol which should be used in such emergencies. Glucagon, a potent positive inotropic agent, overcomes the myocardial depressant effect of propranolol. In centers where propranolol is used for angina pectoris, familiarity with the pharmacologic properties of glucagon should be acquired, so that it can be used, if necessary, in patients developing cardiogenic shock while receiving betaadrenergic blocking agents. Adverse reactions to propranolol have been generally mild and well tolerated, and rarely necessitated its discontinuation. Nausea, abdominal cramps, loose bowel movements, and occasionally diarrhea have been encountered. These are usually transient and become less troublesome after 3 to 6 weeks of treatment. Some patients experience a sedative effect, and several of our subjects complained of a mild fatigue or lack of energy. This is most noticeable in patients whose angina1 symptoms are less severe. In subjects with severe and frequent
Management renal artery
of acute occlusio
Acute and subacute interruption of arterial blood fiow to the kidneys, although not an often recognized clinical entity, is likely to be seen with increasing frequency. Cardiac diseases, such as mitral stenosis, subacute bacterial endocarditis, myocardial infarction, ventricular aneurysms, intracardiac tumors, and septal defects, are frequent causes for emboli to
angina, howe%,-er, this ad~rse effect seems ecirpsed by- the noticeable decrease in angina1 sympzzorns. Propranolol is a potent drug, offering an interesting new concept in the treatment of angina pectoris. its beneficial effects in the short-term treatment of angina are well established and some evidence suggests that it may improve prognosis. There are distinct contraindications to its use, and definite precautions to be followed. It has been our practice to recommend it in the more severely afflicted patients who, in spite of weight reduction and treatment of associated conditions such as hypertension, obtain inadequate relief of symptoms from nitrates. Although the potential hazards of proprano!ol must be stressed, when used properly it is a very effective agent and its results have been gratifying. Its place in the long-term treatment of coronary artery disease is promising, and awaits further experience. Henry F. Y@isgala, il/l.D., F.R.C.P.(C) diam S. Khan, M.D., F.R.C.P.(C) R. 0. Davies, M.D., Ph.D. Division oj Cardiology The Tdontreal General Hospital &lontreai, QrLebec, Canada REFERE,\r :.
2.
\1 . 4.
5.
CBS
l$:olfson, S., Amsterdam, E. ;I., and Gorlin, K.. Prognostic significance of angina therapy: Preliminary report, Circulation 36~274, 1967. Wolfson, S., Heinle, R. A., Michel, V. H., Kemp, 6. H., Sullivan, J. M., and Gorlin, R.: Propranolol and angina pectoris, Amer. J. Cardiol. X8:345, 1966. Mendez, R., and Kabela, E.: Beta receptors in coronary vessels, Lancet 1:907, 1966. Mizgala, H. F., Khan, A. S., and Davies, R. 0.: Propranolol in the prophylactic treatment of angina pectoris, Canad. Med. Ass. J. 100:756, 1969. Aronow, W. S.. and Kaplan, M.: Propranolol combined with isorbide dinitrate versus placebo in angina pectoris, Xew Eng. j. Med. 280:847, 1969.
subac
the peripheral vessels. Thoracoabdominai aorta, :a frequent site of atheromatous plaques and debris, particularly when associated with aneurysma dilatations and tortuosity or surgical manipulations and arteriographic studies of thus region are likely to dislodge and occasionally give rise to embolic occlusion of the renal arteries. The widespr-ead use of
Reflections
on the
Medical and surgical efforts m the treatment 01 angina pectoris due to ischemic heart disease have been mainly directed toward attempts at increasing myocardial blood supply. On one hand, we have seen the introduction and widespread use of a large number of short- or long-acting nitrate preparations, while on the other, our surgical colleagues have devised ingenious methods to promote myocardial revascularization from extracardiac sources. In both instances, their beneficial effects remain the subject of debate and controversy. This is not surprising. Angina pectoris is the subjective manifestation of a disease and is difficult to evaluate obiectivelv. Its natural history is quite variable, and even minor environmental factors can influence results in shortterm clinical trials. Drug evaluations in angina pectoris usually vary in design and often do not assess the stability of the disease during the study. In addition, the exact pathophysiology of angina is poorly understood. While occlusive coronary artery disease is the single most important ana-
cannot judge it from only- one electrocardiogram obtained by this method. This method is useful also in calculating a pulse deficit in rapid atria1 fibrillation, even by a busy nurse at night. In addition, the electrodes-triangle can be used with an electric defibrillator. By connecting the electrodes-triangle to the leads of an electric defibrillator, considerable time is saved in obtaining a prompt diagnosis and treatment of ventricular fibrillation in ward patients for emergency. It has to be emphasized that the electrodestriangle should not be placed close to the chest electrodes for electric discharge in order to prevent a burn at the site of the small eiectrodes by an electric discharge. For an emergency in a ward, the patient-leads of the electric defibrillator always should be connected to the terminals of the electrodes-triangle for ready use. Makoto Tukagi, M.D.
Susumzt Iclzinose, M.D. The Cardiology Bran& Lkfiartment
of Medicine
Kyoto City Hospital Kyoto, Japan REFEREL’CE 1. Green, H. instrument arrhythmias,
roprano
5.: The electrocardiophone: A newfor rapid bedside diagnosis of cardiac Circulation 36:975, 1967.
ect
tomical factor in :is etiology-, other factors may- ‘2 equally important. For example, the oxygen-wasting effect of excessive sympathetic stimulation, with its resulting positive chronotropic and inotropic effects, is well recognized and its deleterious effect in angina is well documented. The recent development of drugs capable of selectively biocking beta-sympathetic receptor sites has provided us with a new approach to the treatment of angina pectoris and has introduced a new pharmacologic tool in the investigation of cardiac function in health and disease. The vast majority of published reports indicate that in well-controlled, short-term clinical trials, propranolol, when given in adequate doses, is effective in reducing the frequency and severity of angina1 attacks and improves exercise tolerance. Indeed, preliminary reports also suggest that in patients with very advanced coronary -artery disease and severe angina, propranolol may influence the natural historv of this disease. Having administered propranolol to such patients, Wlolfson,
Volume Mwmber
80 3
Amsterdam, and Gorlini have reported data suggesting that the incidence of sudden death and acute myocardial infarction seems to be reduced, compared to similar groups receiving more traditional therapy or subjected to internal mammary artery implants. in our own clinic, propranolol is reserved for patients with very severe and intractable angina. Having treated in excess of 150 patients, for periods ranging from 6 months to 3 years, we have been impressed with the relatively low incidence of sudden death and myocardial infarction in a group with such severe disease. Also, in a preliminary trial of propranolol in acute coronary insufficiency, we have administered this drug to 15 patients admitted to the hospital with this syndrome. In all, angina1 symptoms had remained intractable in spite of the usual measures of bed rest, sedation, nitrates, heparin, and digitalis. In 13 of the 15 patients, symptoms subsided immediately. After an average follow-up period of 65 weeks, the course of the disease seems to have stabilized, as none of the 13 patients who initially responded to propranolol developed further episodes of acute coronary insufficiency or acute myocardial infarction. One subject died suddenly, after being free of angina for 67 weeks. The exact mechanism whereby propranolol is effective in angina is uncertain. Its administration is followed by many important hemodynamic changes, resulting both in an increase or a decrease in myocardial oxygen requirements. The bradycardia, the decrease in mean aortic pressure during exercise, the decrease in the rate at which pressure is developed by the ventricle, and the drop in cardiac output all result in decreased myocardial work and oxygen requirement. On the other hand, increased ventricular dimensions during exercise and the relative prolongation of systolic ejection period at rest and exercise tend to augment myocardial work and oxygen demand. In most cases, the net effect is a reduction in myocardial oxygen consumption estimated to be of the order of 25 per cent2 Thus, by blocking myocardial betaadrenergic receptors, propranolol appears to attenuate or prevent the increase in myocardial oxygen requirements resulting from the sympathetic stimulation taking place during exercise or emotional stress. Theoretically, propranolol should produce overall coronary vasoconstriction as cardiac work is reduced. Yet, there is some evidence that in subjects with coronary artery disease, beta-adrenergic blockade may suppress the initial coronary vasoconstriction during spontaneous angina1 attack? or after injection of catecholamines.3 It would be tempting to speculate that in coronary artery disease, it could effect a redistribution of myocardial blood flow favoring the ischemic areas. Propranolol’s quinidine-like action has been stressed. It antiarrhythmic properties may be of some benefit to patients whose angina1 attacks are associated with paroxysmal arrhythmias. Propranolol is a new and exciting addition to our therapeutic armamentarium, and is rapidly gaining favor in the treatment of a variety of cardiac disorders. As its use becomes more widespread, several
9nnotations
429
important considerations must be stressed in assessing its merits in the treatment of angina pectoris. These considerations pertain to the variability in dosage re’quired to produce a response in a group of patients, to potential hazards related to its use, and to adverse effects. It is evident that some patients with angina pectoris do not benefit from propranolol. This lack of response is not related to gastrointestinal absorption, Despite careful comparisons between responders and nonresponders, the phenomenon remains obscure, unexplained, and is unpredictable, so that therapeutic trial becomes necessary. It is also important to recognize that although the average effective daily dose is of the order of 240 mg., it may vary from 60 to 400 mg. Some patients have improvement at a lower dose; in others, significant additional benefit is frequently observed at higher dose levels.4 Thus, controlled clinical trials on a fixed dose may be difficult to evaluate and may, indeed, underestimate the properties of the drug. Beta-adrenergic blockade may, theoretically, induce bronchospasm. Although this has not been a problem in patients with a normal tracheobronchial tree, propranolol should be avoided in patients with a history of asthma and bronchospastic disease. Since propranolol increases atrioventricular conduction time and, by blocking adrenergic receptors, has a pronounced negative chronotropic effect, it is also contraindicated in patients with pre-existing sinus bradycardia or atrioventricular block. The most serious hazard peculiar to the use of propranolol is related to its negative inotropic effect. The sick heart depends on sympathetic tone, and beta-adrenergic blockade may precipitate overt congestive heart failure in patients with borderline compensation. In #our clinic, propranolol is reserved for patients with severe coronary artery disease and intractable angina, in whom pre-existing cardiac reserve is sometimes difficult to assess clinically. Since the positive inotropic effect of digitalis is not reversed by the beta-adrenergic blockade, we prefer to administer digitalis prior to giving propranolol. Failure to do so may, in part, explain the worsening symptoms of angina encountered in some published clinical trials6 In a few patients treated over a long time, we have observed a gradual exacerbation of angina1 symptoms after an initially good response. In several of thlese, the angina was frequently nocturnal. Although tolerance to the beneficial effects of the drug was suspected at first, careful examination indicated fluid retention, and administration of diuretics was promptly followed by amelioration of symptoms. Such patients often require the regular use of diuretic agents, Its use must be avoided in patients with overt congestive heart failure. Its negative inotropic effect also contraindicates its use in patients with mechanical impediments to cardiac function, such as valvular aortic stenosis, significant mitral insufficiency and ventricular dyskinesias, or aneurysms. What happens when a patient receiving propranolo1 develops an acute myocardial infarction? Is propranolol’s myocardial depressant effect a hazard? Does it predispose to intractable cardiogenic shock,
heart block, or asystole? These are important questions which, although not fully answerable at present, merit consideration. Some of our subjects have suffered acute myocardial infarction after an initial beneficial response. Except for sinus bradycardia during the first 24 hours, most have recovered without further complication. However, others have died suddenly and yet others have suffered cardiac arrest while in the hospital with intractable asystole or ventricular fibrillation. In the latter group of patients, severe and very advanced coronary artery disease was demonstrated post mortem. -1lthough we can speculate about the role played by propranolol in their deaths, failure to resuscitate them was probably related to the advanced stage of their disease. Several reports on the use of propranolo1 in acute myocardial infarction have appeared. Intractable shock or asystole did not seem to pose a special problem in these studies. Beta-adrenergic blocking agents inhibit the effect of catecholamines on the myocardium, probably by competitive antagonism at the receptor site. This inhibition can be overcome by sufficiently high concentrations of isoproterenol which should be used in such emergencies. Glucagon, a potent positive inotropic agent, overcomes the myocardial depressant effect of propranolol. In centers where propranolol is used for angina pectoris, familiarity with the pharmacologic properties of glucagon should be acquired, so that it can be used, if necessary, in patients developing cardiogenic shock while receiving betaadrenergic blocking agents. Adverse reactions to propranolol have been generally mild and well tolerated, and rarely necessitated its discontinuation. Nausea, abdominal cramps, loose bowel movements, and occasionally diarrhea have been encountered. These are usually transient and become less troublesome after 3 to 6 weeks of treatment. Some patients experience a sedative effect, and several of our subjects complained of a mild fatigue or lack of energy. This is most noticeable in patients whose angina1 symptoms are less severe. In subjects with severe and frequent
Management renal artery
of acute occlusio
Acute and subacute interruption of arterial blood fiow to the kidneys, although not an often recognized clinical entity, is likely to be seen with increasing frequency. Cardiac diseases, such as mitral stenosis, subacute bacterial endocarditis, myocardial infarction, ventricular aneurysms, intracardiac tumors, and septal defects, are frequent causes for emboli to
angina, howe%,-er, this ad~rse effect seems ecirpsed by- the noticeable decrease in angina1 sympzzorns. Propranolol is a potent drug, offering an interesting new concept in the treatment of angina pectoris. its beneficial effects in the short-term treatment of angina are well established and some evidence suggests that it may improve prognosis. There are distinct contraindications to its use, and definite precautions to be followed. It has been our practice to recommend it in the more severely afflicted patients who, in spite of weight reduction and treatment of associated conditions such as hypertension, obtain inadequate relief of symptoms from nitrates. Although the potential hazards of proprano!ol must be stressed, when used properly it is a very effective agent and its results have been gratifying. Its place in the long-term treatment of coronary artery disease is promising, and awaits further experience. Henry F. Y@isgala, il/l.D., F.R.C.P.(C) diam S. Khan, M.D., F.R.C.P.(C) R. 0. Davies, M.D., Ph.D. Division oj Cardiology The Tdontreal General Hospital &lontreai, QrLebec, Canada REFERE,\r :.
2.
\1 . 4.
5.
CBS
l$:olfson, S., Amsterdam, E. ;I., and Gorlin, K.. Prognostic significance of angina therapy: Preliminary report, Circulation 36~274, 1967. Wolfson, S., Heinle, R. A., Michel, V. H., Kemp, 6. H., Sullivan, J. M., and Gorlin, R.: Propranolol and angina pectoris, Amer. J. Cardiol. X8:345, 1966. Mendez, R., and Kabela, E.: Beta receptors in coronary vessels, Lancet 1:907, 1966. Mizgala, H. F., Khan, A. S., and Davies, R. 0.: Propranolol in the prophylactic treatment of angina pectoris, Canad. Med. Ass. J. 100:756, 1969. Aronow, W. S.. and Kaplan, M.: Propranolol combined with isorbide dinitrate versus placebo in angina pectoris, Xew Eng. j. Med. 280:847, 1969.
subac
the peripheral vessels. Thoracoabdominai aorta, :a frequent site of atheromatous plaques and debris, particularly when associated with aneurysma dilatations and tortuosity or surgical manipulations and arteriographic studies of thus region are likely to dislodge and occasionally give rise to embolic occlusion of the renal arteries. The widespr-ead use of