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The attacks of vasospastic angina or coronary spasm can be induced by injection of epinephrine, cold pressor test, Valsalva maneuver, and exercise. The attacks induced by these procedures can be suppressed by injection of phentolamine, an alpha adrenergic blocking agent in 80 per cent of the patients. On the other hand, propranolol, a beta adrenergic blocking agent, is not only ineffective in suppressing the attacks but aggravates the attacks in 50 per cent of the patients. Thus, alpha adrenergic receptors seem to play an important role in the production of vasospastic angina. The attacks of vasospastic angina can also be induced by injection of methacholine, a parasympathomimetic agent, and this reaction is suppressed by atropine, a parasympathetic blocking agent. Thus, parasympathetic nervous system also seems to play a role in the production of vasospastic angina. The attacks of vasospastic angina can be easily induced by adrenergic or parasympathetic stimuli from midnight to early morning but is usually not provoked by these stimuli in the daytime. Thus, there is circadian variation in the reactivity of coronary arteries to adrenergic or parasympathetic stimuli. There are also weekly, monthly and yearly variations of the reactivity of coronary arteries to these stimuli. Thus, alpha adrenergic or parasympathetic activity is not the sole factor in the production of vasospastic angina. Angina pectoris caused by increased myocardial oxygen demand is induced by infusion of isoproterenol, a beta adrenergic stimulant, and is suppressed by propranolol but not by phentolamine. So, beta adrenergic receptors play an important role in the production of angina pectoris caused by increased myocardial oxygen demand or organic angina pectoris.

To determine whether calcium-flux blockade with nifedipine blunts coronary vasospasm, four patients with angiographically demonstrable coronary arterial spasm in the absence of significant fixed coronary arterial stenosis were evaluated with coronary arteriography before and after treatment with nifedipine. After initial coronary arteriography, ergonovine was administered in successive doses of 0.05, 0.1 and (when necessary) 0.2 mg intravenously at 3 minute intervals. Three patients had symptomatic high grade focal coronary arterial spasm with electrocardiographic changes, and the fourth exhibited asymptomatic 60 percent constriction of the left anterior descending coronary artery. A maximal ergonovine challenge was repeated 30 minutes later after each patient had been pretreated with a 20 mg sublingual dose of nifedipine. Under these conditions, no patient had chest pain or electrocardiographic changes. Furthermore, neither focal nor diffuse coronary arterial spasm was demonstrable angiographically after the second challenge. Thus, in each case, a single dose of nifedipine precluded the angiographic expression of ergonovine-provoked coronary arterial spasm.

Six patients who had documented coronary spasm and no coronary artery with organic obstruction greater than 50% developed angina and ST-segment elevation on exercise testing. Oral verapamil, 160-480 mg/day, prevented exercise-induced ischemia in all patients and increased maximal work capacity from 611+/- 250 kpm to 808 +/- 160 kpm (p less than 0.02). In two patients, a relationship between the prevention of exercise-provoked ischemia and the plasma concentration of verapamil was demonstrated, and in one of these, the relationship had a diurnal pattern. Patients with variant angina may develop coronary spasm on effort and often respond to verapamil.

Thromboxane A2 (TxA2), an arachidonic acid metabolite causing vasoconstriction and platelet aggregation, is a putative mediator of coronary-artery vasospasm. To determine whether platelet-released TxA2 causes coronary arterial vasospasm, we measured plasma thromboxane B2 (TxB2, the inactive hydration product of TxA2) in the radial-artery and coronary-sinus blood of seven patients and performed therapeutic trials of antiplatelet agents in nine. Although coronary-sinus TxB2 levels rose from the base line approximately fivefold with spontaneous ischemia, samples drawn early in ischemia showed no rise over base-line values. Although a 150 mg dose of aspirin reduced urinary dinor-TxB2 levels by over 75 per cent, it had no effect on the course of the chronic recurrent form of angina pectoris due to vasospasm ("vasotonic angina"). Similarly, indomethacin had no effect on the frequency or duration of ischemia. TxA2 is unlikely to cause vasotonic angina, but it may be released during coronary vasospasm.

Five male patients, aged between 31 and 58 years, presented with anginal chest pain with nausea and sweating after the interruption of exercise. Prinzmetal variant angina was observed during the recovery phase of exercise tolerance testing. Coronary arteriography and selective left ventricular angiography were normal in all cases. Ergonovine, used in one case, induced coronary artery spasm. The angina was eased by Nifedipine in three patients and passed off with time in the other two patients. In one case attack occurred with amiodarone therapy and in another with glyceril trinitrate, after normal exercise tolerance tests. Vagotonia, all the more pronounced when sympathetic tonus is increased, and hyperventilation seem to be the causative factors of what probably results from coronary artery spasm. Nifedipine, a calcium-blocking agent would appear to be the treatment of choice.

A young man with a single left coronary artery and refractory variant angina is described. Spontaneous coronary artery spasm developed during coronary arteriography at the site of a 50% fixed left anterior descending coronary artery stenosis. Frequent episodes of rest angina with transient ST segment elevation persisted in hospital in spite of treatment with three different calcium antagonist drugs. Symptoms disappeared only when the combination of nifedipine, diltiazem, isosorbide dinitrate, and nitroglycerin ointment were given. Ergonovine testing was used to objectively assess the response to treatment.

A 24-year-old male student had three myocardial infarctions, one prior to and two following the angiographic documentation of normal coronary arteries. A spontaneous episode of variant angina prompted repeat coronary angiography, during which intravenous ergonovine caused spasm of the left anterior descending coronary artery, transient ST-segment elevation, and ischemic chest pain; the previously normal right coronary artery was found to be occluded proximally. This constellation of clinical and angiographic findings suggests that coronary spasm can cause acute myocardial infarction as well as variant angina.

The unique association of both exercise-induced coronary arterial spasm and S-T segment depression with normal findings on selective coronary arteriography is described. The patient had a prior history of typical effort angina that had recently progressed to angina at rest. Despite the change in anginal pattern, the electrocardiogram disclosed S-T segment depression that was consistent with subendocardial ischemia, during both exercise testing and spontaneous chest pain. Exercise thallium-201 scintigraphy demonstrated the presence of large perfusion defects of the anterior and septal walls of the left ventricle. Coronary arteriographic findings, in the absence of symptoms, were entirely normal. Severe localized, reversible coronary spasm of the proximal left anterior descending coronary artery was subsequently demonstrated during spontaneous angina, isometric arm exercise and after the administration of ergonovine maleate. After treatment with isosorbide dinitrate and nifedipine, the patient had no further chest pain or electrocardiographic changes, and a repeated thallium-201 stress test revealed normal findings and greatly improved exercise tolerance.

A 57-year-old man with atypical progressive angina caused by congenital coronary-pulmonary shunt and coronary atherosclerosis is described. The angina was rather consistently unresponsive to nitroglycerin. Following closure of the shunt and aortocoronary bypass surgery, the patient became asymptomatic and has remained free of angina 2 year postoperatively. Although the congenital anomaly is rare in adults, it may be considered in the differential diagnosis of atypical angina pectoris, particularly when there is either continuous murmur or systolic murmur over the lower parasternal area.

Spasm of a large coronary artery occurs most often from midnight to early morning and least often in the afternoon, due to the circadian variation of the tone of the large coronary artery in most patients with variant angina. Alpha adrenergic stimulation induces coronary spasm most easily in the early morning and least easily in the afternoon. Coronary spasm is due to strong contraction of coronary vascular smooth muscle cells which is triggered by an increase of intracellular calcium ions; hyperventilation plus TRIS-buffer infusion induces coronary spasm by decreasing hydrogen ions which antagonize the action of calcium ions. Administration of nitroglycerin promptly relieves the acute attack of coronary spasm, and calcium antagonists such as diltiazem, nifedipine and verapamil, which block the entry of calcium ions into coronary vascular smooth muscle cells and dilate large coronary arteries, prevent the occurrence of coronary spasm.

In 3 patients with Prinzmetal's variant angina there were inferior epicardial injury patterns on the electrocardiogram, corresponding to right coronary artery narrowing. Attacks were provoked by beta-adrenergic blockade and stopped by nitroglycerine and atropine. Spasm of the right coronary artery was demonstrated in the 2 patients who had high parasympathetic activity. In all 3 cases attacks disappeared on verapamil. We suggest that calcium-antagonists, which dilate the coronary arteries, should be used in the treatment of Prinzmetal's angina pectoris rather than beta-adrenergic blockers, which do not have this property.

The prevalence rate of exercise- S-T segment elevation of 0.1 mV or greater in symptomatic patients is 3.0 to 6.5 percent in most studies. S-T segment elevation is associated with a more severe degree of myocardial ischemia than depression and frequently implies a high grade coronary stenosis in the vessel that supplies the site of ischemia. Leads V4 to V6 and bipolar lead CM5 have been found to be relatively insensitive in detecting exercise-induced S-T segment elevation. The pathogenesis of S-T segment elevation is different in three clinical patient subsets reviewed. In patients afer infarction, the largest of the three subgroups, exercise-induced S-T segment elevation usually appears in leads with Q waves, is more common after anterior myocardial infarction and implies underlying akinetic of dyskinetic wall motion. Of patients with variant angina, 10 to 30 percent have during exercise S-T segment elevation that is most likely provoked by coronary arterial spasm. The natural history of variant angina is cyclic, and clinical observations and laboratory findings are dependent on particular phases in the disease process and treatment. Finally, 0.2 to 1.7 percent of symptomatic patients without infarction or variant angina have exercise-induced S-T segment elevation. Although most of the latter have fixed high grade coronary arterial stenoses at angiography, the exact pathogenetic mechanism of S-T segment shift in this patient group is not yet fully understood.

71 patients undergo myocardial revascularisation for Prinzmetal's angina; among them, 50 p. cent are operated upon in emergency according to three ways of anaesthesia: neuroleptanalgesia, analgesic anaesthesia, combined anaesthesia. The authors lay stress on the importance of per- and post-operative complications: electrocardiographic ischemia in 22 p. cent of the cases, severe ventricular excitability perturbations were observed in 21 p. cent, myocardial necrosis in 14 p. cent, cardiovascular collapse in 21 p. cent and hypertensions in 22 p cent. These complications are often associated. In the discussion, the authors underline anesthetic induction as a cause of Prinzmetal's angina in 50 p. cent of the cases. They put the accent on the severity of peroperative crisis followed in 50 p. cent of the cases by serious ventricular excitability perturbations. In 25 p. cent of the cases myocardial necrosis is a complication of the spasm of a coronary artery. In this field, posterior necrosis are more frequent and correspond to the spasm of the right coronary artery. All the patients of this series, except one, develop necrosis in the spastic area (by-passed or not). Per-operative hypertension has no incidence on the occurrence of post-operative complications. Lastly, continuous per-operative infusions of nitroglycerine has been performed in several patients in order to reduce morbidity of this type of surgery.

The authors have studied the frequency and severity of anginal attacks of the Prinzmetal type coming on during the acute phase of a myocardial infarction in 13 patients. They have occurred in 5.50% of cases (anginal attacks of all types occurring in 18.34% of cases). The severity of these attacks is shown by their clinical features: the multiplicity of the attacks, the high incidence of arrhythmias, the difficulties encountered with medical treatment. This also confirmed by the enzyme studies: when the curve of myocardial creatinine kinase release is drawn, there is seen to be an extension of the lesion in 2/3 cases, whereas the electrocardiograph does not show this up.

Angina pectoris is a clinical syndrome caused by transient myocardial ischaemia due to an imbalance between myocardial oxygen demand and supply. It is now evident that coronary artery spasm plays an important role in the pathogenesis of various forms of angina pectoris. Angina pectoris that is mainly caused by coronary artery spasm (coronary spastic angina) has one or more of the following characteristics: 1) the attack occurs at rest, 2) the attack is associated with ST-segment elevation in the ECG, 3) the attack has a variable exercise threshold, and 4) the attack is suppressed by Ca-antagonists but not by beta-adrenergic blocking agents. On the other hand, angina pectoris that is caused by increased myocardial oxygen demand in the presence of severe and extensive organic stenosis (organic angina) has the following characteristics: 1) the attack is induced by constant amount of exertion irrespective of hour and day and is relieved by rest, 2) the attack is associated with ST-segment depression in the ECG, and 3) the attack is suppressed by beta-adrenergic blocking agents, which decrease myocardial oxygen demand.

31 patients presenting with Prinzmetal variant angina were divided into three groups according to their angiographic appearances. Group I comprised 9 patients with normal or coronary arteries with lesions less than 50% narrowing. Group II comprised 12 patients with single vessel disease. Group III comprised the other 10 patients with significant lesions on two or all three principal arteries. No clinical or electrocardiographical differences were found between the groups as to age, sex or the clinicapresentation of the chest pain. Most patients with normal or nearly normal coronary arteries had normal electrol cardiogrammes between attacjs (8 out of 9) and electrical changes mainly over the inferior wall (8 out of 9). Exercise electrocardiography reproduced ST elevation in 4 of the 9 patients but, in contrast to the patients in the other two groups, never ST depression. However, these features are not specific for patients in Group I as they were observed in 4 patients in the other two groups. Spontaneous or induced coronary spasm were observed in 27 patients, confirming its role as the mechanism of Prinzmetal angina, whatever the anatomical appearance of the coronary tree.

A 32-year-old male with the clinical syndrome of unstable angina is presented. During cardiac catheterization and coronary cineangiography, the coronary arteries were found to be free of atherosclerosis, but segmental spasm of the right coronary artery was observed. Spasm was reproduced, but to a milder degree, upon the administration of ergonovine maleate intravenously. The patient was discharged on a regimen of oral nylidrin HCL, with symptomatic improvement.

A 49 year old man had severe refractory Prinzmetal's variant angina and angiographically documented coronary arterial spasm of a dominant circumflex artery. The spasm was provoked by methergine (an ergot alkaloid) and seemed resistant to various forms of medical therapy including administration of nitrates, nifedipine, verapamil, diltiazem and amiodarone. The attacks of angina at rest persisted at the rate of 7 to 15/day and were frequently associated with atrioventricular (A-V) block. After unsuccessful plexectomy performed in another institution, the patient underwent complete cardiac denervation (produced by autotransplantation). The follow-up data have interesting implications in relation to treatment of refractory variant angina, as well as possible mechanisms of coronary arterial spasm.

The study reports on the outcome of hyperventilation tests in a 57-year-old male with Prinzmetal's variant angina, formerly often complicated by ventricular fibrillation. It was found that hyperventilation for a period of 6 min after a delay of 4 to 6 min was followed by the development of ST-elevation and pain, but only when the test was performed in the morning, whereas the outcome of tests performed later in the day were negative. Pretreatment with calcium blockers, nifedipine or verapamil proved effective in preventing the anginal response to the test, also when it was performed in the morning. It is concluded that hyperventilation performed in the early morning, but not later in the day, may prove to be an effective and safe procedure for provoking Prinzmetal's variant angina, and that hyperventilation may be useful in the evaluation of the efficacy of drug therapy.

Patients who present with episodes of angina caused both by an increase in oxygen demand and by transient impairment of supply have a mixed form of angina. Distinctive clinical features allow the classification of patients in everyday practice. At one end of the spectrum are patients who have angina only and always when they exercise beyond an essentially fixed level; their angina is fairly predictable and has been termed secondary angina. At the other end of the spectrum are patients who have a normal exercise tolerance but have angina at rest or during activities usually well tolerated that must be caused by a transient impairment of coronary blood flow; their angina is typically unpredictable and has been termed primary angina. We adopted the term primary to emphasize the possible existence of multiple causes of impairment of coronary flow, which together are to be contrasted with the traditional prevailing concept of angina being secondary to excessive increase in demand. In between these ends of the spectrum are most of the patients with angina pectoris encountered in clinical practice: they have a rather predictable ceiling of exercise that they cannot exceed without developing angina, but they also have a variable proportion of unpredictable anginal attacks that occur spontaneously or at levels of activity that are usually well tolerated. We introduced the concept of mixed forms of angina when we became aware that the same patient could experience angina both as a result of an excessive increase in myocardial demand, i.e., secondary angina, and as a result of the transient impairment of coronary blood flow supply, i.e., primary angina.

The case reported analyses the instantaneous revascularisation distal to a coronary spasm by electrocardiography and thallium scintigraphy. The patient, a 48 year old man, had an 18 months history of spontaneous anginal chest pain sensitive to trinitrin. No electrocardiogrammes had been recorded during an attack. Coronary angiography was normal apart from a slight reduction in calibre of a dominant right coronary artery. Injection of 0.4 mg methylergometrine provoked an occlusive spasm of this artery after 4 minutes. At the same time the patient experienced angina and 4,5 mm depression of the ST segment, without ST changes in D3 and AVF, was observed. Opacification of the left coronary artery during spasme of the right showed retrograde revascularisation of the posterior interventricular artery which was reversed when the coronary spasm was terminated with trinitrin. Thallium scintigraphy was performed during another spasm provocation test four days later which gave identical clinical and electrical changes. A zone of hypofixation with blurred limits over the inferior myocardial wall was demonstrated. In the absence of ST elevation and of lacuna on myocardial scanning, the myocardial ischaemia induced by this occlusive spasm could not be considered to be total. Therefore the immediate revascularisation of the coronary artery in spasm seemed to have played the role of an effective collateral circulation.

From among 899 consecutive patients who underwent their first coronary arteriography, we selected 147 pts with vasospastic angina (VA) and 356 pts with classic angina (CA) and divided them into three different age groups: -49 years old, 50 to 59, and 60-. In these 899 pts, incidences of VA showed no increase with aging. Prevalence of coronary risk factors in CA, such as diabetes, hypercholesterolemia, hypertension, and obesity, was higher than in VA, although prevalence of smoking in CA was lower than in VA. In VA, we found an age-related increase in the incidence of smoking only, in contrast to the other four risk factors. The VA showed no age-related increase in the incidence of complication of fixed coronary stenosis. These findings suggest that aging and atherosclerosis might not play a major role in pathogenesis of VA, although the mere presence of atherosclerosis irrespective of its severity could interact with local susceptibility to spasm, leading to coronary vasospasm.