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The aim of this study was to investigate the role of nitric oxide (NO) in the coronary circulation and its relation to basal coronary artery tone in patients with vasospastic angina (VSA). We evaluated the level of nitric oxide end-products (NOx; nitrite + nitrate) in coronary circulation blood using an HPLC-Griess system for nine patients with VSA and nine control patients. All of the patients with VSA experienced focal spasm in the proximal to middle segments of the left anterior descending coronary artery (LAD) in response to intracoronary injection of ergonovine maleate. The luminal diameter of the coronary artery was measured in each patient by quantitative coronary arteriography. Blood samples for NOx measurement were obtained from the coronary sinus (NOxV) and the ostium of the left coronary artery (NOxA). The NOx difference, calculated from the coronary venous-arterial difference in NOx, was close to zero for the control patients whereas it was clearly negative for the patients with VSA. In addition, the NOx difference in the patients with VSA showed a negative correlation with basal coronary artery tone (r = -0.91, p < 0.01) and a positive correlation with the dose of ergonovine required for spasm provocation (r = 0.77, p < 0.05). These results indicate that increased basal coronary artery tone and higher susceptibility to ergonovine in patients with VSA would be a consequence of coronary endothelial dysfunction as is indicated by NOx.

The aim of this study was to assess whether the psychobehavioral pattern alexithymia is related to coronary artery spasm. Alexithymia, deficient psychological awareness, was examined using the Minnesota Multiphasic Personality Inventory Alexithymia Scale in 100 patients with angina pectoris in whom coronary spasm, defined as > or = 99% coronary narrowing, was documented upon ergonovine provocation, and in 109 patients with chest pain syndrome who were shown to have almost normal coronaries without inducible coronary spasm on coronary angiogram (control group). Alexithymia was approximately twice as prevalent in the coronary spasm group (31%) as in the control group (14%) (p<0.01). Among various conventional risk factors including hyperlipidemia, obesity, diabetes mellitus, hypertension, hyperuricemia, or family history of ischemic heart disease, only male sex and smoking were more prevalent in the coronary spasm group than in the control group (p<0.001). The odds ratios of coronary spasm adjusted for all the other risk parameters including sex and age were 4.14 [95% confidence interval (CI) 1.81-9.47] for alexithymia and 2.38 (95, CI 1.18-4.82) for smoking. A psychobehavioral pattern, alexithymia, relates to coronary spasm. This relationship is independent of the conventional coronary risk factors.

Ergot alkaloids, produced by the fungus Claviceps purpurea, are found in small amounts in foodstuffs. The human disease ergotism, caused by high intake of ergot alkaloids, is well known; however, little is known about the toxicity of these compounds. The subacute toxicity of an ergot alkaloid, ergometrine maleate, was therefore studied. Sprague-Dawley rats were treated with 0, 2, 10, 50 and 250 mg ergometrine maleate/kg diet for 4 wk. Plasma glucose levels were decreased in females at 50 and 250 mg/kg. Thyroxin levels were decreased at 50 (males only) and 250 mg/kg. At the high dose level, organ weights of heart, liver, ovaries and kidneys were increased. In male rats a slight dose-related increase in the incidence of enlarged mediastinal lymph nodes and, to some extent, of enlarged parathymal lymph nodes, was seen. Histopathological examination revealed evidence of increased glycogen storage in the liver of animals treated with 250 mg/kg. The no-observed-effect level in this study was 10 mg/kg.

Objectives: The purpose of this study was to use intravascular ultrasound imaging to examine the presence of occult atherosclerosis at the site of focal vasospasm in angiographically normal or minimally narrowed segments, testing the role of atherosclerosis in the development of vasospasm., Background: Previous clinical and experimental studies have suggested that early atherosclerosis is present at the site of focal vasospasm. However, no clinical data exist demonstrating occult disease at the site of vasospasm at angiographically insignificant stenoses., Methods: Twenty-two patients with chest pain at rest or during exertion, or both, were studied. Vasospasm was provoked by intracoronary administration of ergonovine maleate (0.01 to 0.04 mg). After relief of vasospasm by nitroglycerin administration, intravascular ultrasound imaging was performed with a 32- or 64-element, 20-MHz, synthetic aperture array ultrasound device., Results: Focal vasospasm (arterial diameter reduction > or = 90%) with ST-T segment elevation was provoked in 15 patients: in the left anterior descending coronary artery in 8 patients and in the right coronary artery in 7. The remaining seven patients (control group) showed diffuse narrowing, averaging 22 +/- 12% (mean +/- SD) in diameter from the baseline angiograms after ergonovine administration. Atherosclerosis, defined as a significantly thickened intimal leading edge (0.42 +/- 0.07 mm) associated with an increased sonolucent zone (0.57 +/- 0.30 mm), was detected by ultrasound at all 15 sites with focal vasospasm, although these sites were normal or minimally narrowed by angiography. In contrast, seven segments from the control group exhibited a thin intimal leading edge (0.14 +/- 0.04 mm, p < 0.01) and sonolucent zone (0.10 +/- 0.07 mm, p < 0.01), indicating the absence of localized atherosclerotic lesions., Conclusions: These results indicate that atherosclerosis is present at the site of focal vasospasm, even in the absence of angiographically significant coronary disease. We suggest that the existence of such atherosclerotic lesions is related to the occurrence of focal vasospasm in the clinical settings.

Objectives: This study was conducted to establish whether changes in myocardial texture can be observed in humans by transthoracic echocardiography during ischemic episodes of different severity and duration induced by various pathogenetic mechanisms., Background: Increased echo-reflectivity of ischemic myocardium has been detected in experimental animals by epicardial echocardiography and by backscatter evaluation., Methods: Transthoracic two-dimensional echocardiographic monitoring with a commercially available electronic sector scanner (2.25- or 3.5-MHz transducer) was performed during 35 episodes of transient myocardial ischemia induced by ergonovine in patients with vasospastic angina (n = 9), by dipyridamole in patients with angiographically assessed coronary artery disease (n = 11) and by balloon occlusion during coronary angioplasty (n = 15). Quantitative texture analysis of gray levels was performed off-line on digitized images during rest conditions, ischemia and the recovery phase in regions showing normal contraction at rest, obvious dyssynergy during ischemia and normal contraction in the recovery phase. In each condition, a control region with normal contraction throughout the study was also evaluated., Results: Chest pain occurred in 23 of the 35 episodes; electrocardiographic (ECG) changes were present in 26 episodes, and consisted of ST segment elevation in 13, ST segment depression in 10 and pseudonormalization of a basally negative T wave in 3. The duration of ischemic episodes was 67 +/- 53 s by symptomatic criteria and 91 +/- 52 s by ECG criteria. The risk region showed an increased end-diastolic mean gray level amplitude in a.u. (arbitrary units) during ischemia (57 +/- 19) compared with rest (38 +/- 15) and recovery (38 +/- 18, p < 0.01). No significant changes were detected in the control region (rest 36 +/- 16 vs. ischemia 34 +/- 18 vs. recovery 31 +/- 13, p = NS). The percent increase in mean gray level was similar in the various types of stress employed (ergonovine, dipyridamole or angioplasty) and was not significantly correlated with either the duration of ST segment shift (r = 0.05, p = NS) or the severity of dyssynergy evaluated semiquantitatively by means of the wall motion score (r = 0.28, p = NS). In the 15 balloon occlusions performed in six patients during coronary angioplasty, the increased echoreflectivity of the risk zone was already evident during echocardiographic sampling performed after 10 +/- 4 s of occlusion (rest 35 +/- 9 vs. 53 +/- 10 a.u., p < 0.01) when no dyssynergy could be detected by quantitative wall motion analysis (percent area change by fixed center of mass reference system 31 +/- 10% at rest vs. 32 +/- 11% after 10 s of occlusion, p = NS)., Conclusions: Transient short-lasting myocardial ischemia is associated with an abrupt increase in myocardial echodensity detectable by videodensitometric analysis applied to standard transthoracic echocardiographic images and is largely independent of the underlying pathogenetic mechanism (reduced blood supply or flow maldistribution with coronary stenosis). During controlled coronary occlusion, increased echodensity precedes the onset of regional dyssynergy.

The utility of ergonovine testing for coronary artery spasm was assessed in 3,447 patients with angiographically insignificant (less than 50% diameter stenosis) or no coronary artery disease. No patients clinically had Prinzmetal's variant angina. Overall, 4% had a positive ergonovine test result, defined by spasm causing greater than or equal to 75% focal stenosis. Complications related to ergonovine use occurred in 11 patients (0.03%). In a training sample of 1,136 patients (studied between 1980 and 1984), two independent predictors of spasm were found by using multivariate analysis: the amount of visible coronary artery disease on the coronary angiogram (p less than 0.0001) and a smoking history (p = 0.001). A model to predict spasm based on these variables was validated in a test group of 2,311 patients who received ergonovine from 1985 to 1989. This model allowed the identification of a subset of 400 patients in the validation sample who had a 10% positive test rate compared with a 2% positive test rate in the remaining patients. These results should permit clinicians who use provocative testing in the catheterization laboratory to reserve testing for the subset of this group of patients most likely to have abnormal findings.

The left ventricular filling and regional wall motion patterns were compared in 6 normal subjects, 20 patients with coronary artery disease, and 10 patients with syndrome X by means of Doppler and two-dimensional echocardiography during high-dose (0.9 mg/kg body weight in 10 min) dipyridamole infusion. During the procedure none of the normal subjects had chest pain or significant ST depression (greater than 0.1 mV) whereas 10 of 20 patients with coronary artery disease had ST depression, 3 with chest pain. Six patients with syndrome X had ST depression, 5 with chest pain. Regional wall motion abnormalities were identified in 6 patients with coronary artery disease who had ST depression but none were detected in normals or in patients with syndrome X. Compared with normals (-2.1 +/- 3.5%) there was a significant difference in percentage decrease in the peak early filling velocity in patients with coronary artery disease and ST depression (-10.3 +/- 6.2%; p less than 0.01) and in patients with syndrome X and ST depression (-9.4 +/- 6.9%; p less than 0.05). These findings indicate that, in the presence of dipyridamole-induced ST depression, patients with syndrome X have an abnormal left ventricular filling pattern similar to that observed in patients with coronary artery disease. This suggests that myocardial ischemia occurs in patients with syndrome X but the absence of regional wall motion abnormality suggests that it is diffuse.

The aim of the study is to evaluate the reproducibility of exercise testing and to determine whether there is any correlation between the reproducibility of exercise test and response to the ergonovine maleate test. Thirty-eight patients with mixed angina and documented coronary artery disease underwent an ergonovine maleate test and four exercise tests on consecutive days in the same basal conditions. The ergonovine test was positive in 20 patients (Group I) and negative in 18 patients (Group II). There were no significant differences in the clinical and angiographic data of the two groups. All 152 exercise tests were positive. The variability of the response of the repeated tests was assessed by means of an analysis of the following parameters: heart rate, blood pressure, rate-pressure product, watts, and minutes were recorded at the onset of ischemia (ST decreases greater than or equal to 0.1 mV). Range (maximal-minimal obtained value), ratio between range and maximal obtained value, and coefficient of variation (standard deviation/mean of the four parameters) were calculated for each patient. The analysis of these values demonstrated that while the test was reproducible in some patients, a high individual variability was present in others. Moreover, the individual variability results were higher in Group I than in Group II, with a statistically significant difference for all considered parameters. In conclusion, it is possible to have a poorly reproducible exercise test in patients with mixed angina. The correlation between a positive ergonovine test and a poorly reproducible exercise test suggests that abnormal coronary vasomotion may sometimes be present during exercise and may affect the reproducibility of the test.

Ergonovine maleate produced transient vasospastic occlusion of the entire left anterior descending coronary artery in a young woman with atypical angina pectoris and normal coronary arteries. Electrocardiographic evidence of extensive anterior subendocardial ischaemia persisted for days after an episode of spontaneous pain, suggesting that the patient was at risk of developing completed infarction due to coronary spasm.

A revised scheme of management of the third stage of labour was recently introduced in the Midwife Obstetric Units in Cape Town. Patients received synthetic oxytocin (Syntocinon; Sandoz) 5 IU intramuscularly with the delivery of the anterior shoulder and ergometrine maleate 0.5 mg intramuscularly after delivery of the placenta. A significant decrease in the incidence of postpartum haemorrhage and retained placenta was observed, warranting continuation of the new regimen.

In many patients with chest pain of esophageal origin, findings are normal on routine esophageal manometry and dysmotility develops only upon provocation with ergonovine maleate. Unfortunately, ergonovine may induce myocardial ischemia in patients in whom coronary artery spasm did not occur during previous provocative testing in a cardiac laboratory-limiting its clinical usefulness. We have recorded esophageal pressure simultaneously with ergonovine infusion during angiography in ten patients without significant arterial stenoses. In two patients their usual chest pain developed associated with esophageal spasm and without changes in coronary vessels. Simultaneous performance of angiography and manometry enhanced the diagnostic yield of provocative testing by showing esophageal motility changes. This method may detect significant changes in the esophageal motility, is easy to carry out and does not interfere with angiography. It maximizes the information gained from a single provocative test and avoids the risk of ergonovine infusion outside of a cardiac laboratory.

The organic stenosis of the coronary artery and vasospasm induced by ergonovine maleate (EM) were examined by cine angiography in 106 cases with unstable angina. They were divided into 5 groups: new angina at rest (27 cases), new angina of effort (15 cases), changing pattern from effort to rest (41 cases), crescendo-type angina at rest (20 cases) and changing pattern from rest to effort (3 cases). The following results were obtained: The incidence of a 75% or more organic stenosis was significantly lower in new angina at rest (52%) and crescendo-type angina at rest (55%) than in changing pattern from rest to effort (95%) (p less than 0.005). The incidence of a 90% or more organic stenosis was significantly lower in new angina of effort than in changing pattern from effort to rest (46% vs 88%, p less than 0.01). On the other hand, the incidence of a 50% or more spastic narrowing provoked by EM was 94% in new angina at rest, 90% in crescendo-type angina at rest, 56% in new angina of effort and 64% in changing pattern from effort to rest. In all 3 cases of changing pattern from rest to effort, total obstructions due to coronary spasm were found. However, there were no significant differences among these groups.

The features of ventricular arrhythmia in coronary spasm induced by ergonovine were examined to elucidate the characteristics of ventricular arrhythmia in acute myocardial ischemia. The coupling intervals and configurations of the QRS wave of the premature ventricular beats (PVBs) were extremely variable, even in the same individual and at the closer time phases. The prematurity index (R-R'/QT) of PVBs with the right bundle branch block (RBBB) pattern was significantly smaller than with the left bundle branch block (LBBB) pattern. The vulnerability index (R-RX QT/R-R') of PVBs with the RBBB pattern was significantly larger than with the LBBB pattern. The incidence of PVBs with the RBBB pattern (50.4%) was slightly larger than with the LBBB pattern (40.5%). PVBs deteriorated into ventricular tachycardias (VTs) in 29 (24.8%) of 117 cases with the RBBB pattern and in 11 (11.7%) out of 94 cases with the LBBB pattern. Thus, PVBs with the RBBB pattern were more likely to progress to VT than with the LBBB pattern. But it is difficult to assess the clinical significance of PVBs from their QRS morphology alone, because 11 (27.5%) of 40 cases of VT were initiated by PVBs with the LBBB pattern.

A 54-year-old man developed angina pectoris 18 months after a successful aortocoronary bypass graft. The angiogram demonstrated patent grafts and no significant changes in the native coronary vessels. However, ergonovine maleate provoked spasm in a saphenous vein graft.

Sequential 12 lead electrocardiograms were recorded during angina pectoris induced by ergonovine maleate in 38 patients with variant angina. Transient U wave inversion was observed in 17 patients with ST segment elevation in anterior chest leads, but in only three of 21 patients with ST segment elevation in the inferior leads associated with right coronary artery spasm. In the 17, all of whom had spasm of the left anterior descending coronary artery, the sensitivity of ST segment elevation in V5 was only 41%, and that of U wave inversion 71%. U wave inversion without ST segment elevation occurred during attacks in 35% of patients. During the recovery phase, the sensitivity of U wave inversion was 82% in V4 and 65% in V5, though ST segment elevation was absent in both V4 and V5. Thus, inverted U waves without ST segment elevation often appear in marginal ischaemic zones or during the time of recovery from temporary ischaemia. Detection of inverted U waves should aid in the diagnosis of variant angina when only lead V5 is used as a monitor and when electrocardiograms are recorded only during the recovery phase.

Four patients with medically refractory unstable angina are presented. Each patient had ST-segment abnormalities during some episode of pain. Three patients had at least one episode of documented ST-segment elevation with their spontaneously occurring chest pain. One had recurrent ventricular tachycardia. Two patients had prior myocardial infarction. Angiography demonstrated localized left ventricular akinesis and a severe fixed stenosis in the coronary artery supplying the abnormal segment. There were severe, fixed lesions in two coronary arteries in two patients and in one vessel in two patients. After i.v. ergonovine maleate, coronary artery spasm was documented in a normal or minimally diseased coronary artery in each patient. In two patients, ergonovine-induced spasm not only occluded the vessel, but also markedly decreased retrograde filling of a vessel with severe, fixed narrowing. Each patient's characteristic symptoms appeared with the ergonovine-induced spasm. Thus, ergonovine maleate can provoke spasm of a normal coronary artery, even in the presence of severe fixed stenoses of the remaining vessels. This observation may have an important role in the diagnosis and clinical management of patients with chest pain.

It has been postulated that even moderate spasm in an artery with intimal hyperplasia can produce organ hypoxia because there is an excessive reduction in the diameter of the lumen. To test this hypothesis we created intimal hyperplasia in one femoral artery in five pigs and then induced arterial spasm by administering ergonovine maleate. Arterial spasm did not produce a greater reduction in the luminal diameter of the femoral artery with intimal hyperplasia than it did in the normal femoral artery. Until further evidence appears this hypothesis must be viewed with caution.

Unusual vasomotor responses in the coronary arteries occurred in two patients after the administration of glyceryl trinitrate to relieve spasm induced by ergonovine maleate. In one patient after treatment with glyceryl trinitrate and despite dilatation of the adjoining segments a new severe reduction in diameter occurred distally to the segments of the right coronary artery where the ergonovine induced spasm developed. In the other patient the left anterior descending artery filled very slowly after the completely occlusive spasm of the right coronary artery had resolved with glyceryl trinitrate though the circumflex did not. These vasomotor changes were associated with chest discomfort and electrocardiographic abnormalities in both cases. These findings indicate that caution is needed when performing provocative tests even after the ergonovine induced spasm has been reversed with glyceryl trinitrate.

The case of a patient with severe left main trunk disease is presented, in which spasm of the right coronary artery resulted in intraoperative myocardial ischemia and perioperative myocardial infarction. It is suggested that coronary spasm may be a cause of perioperative myocardial infarction, and has to be considered in case of unknown etiology.

The haemodynamic response to myocardial ischaemia in patients with variant angina during ambulatory activity is unknown. Ambulatory pulmonary artery pressure monitoring with a transducer tipped catheter and simultaneous frequency modulated electrocardiograms was used to assess changes in left ventricular function in five male patients (mean age 51.8 years) during variant angina; four patients had coronary artery stenosis and one had normal coronary arteries. Two hundred and seventy hours of ambulatory recordings were analysed. Twenty episodes (12 painful, 8 silent) of ST segment change greater than 1 mm occurred. Episodes tended to occur more frequently in the early morning hours. Six episodes of painful ST elevation were associated with a rise in pulmonary artery diastolic pressure. In the remaining episodes ST segment elevation was of shorter duration and there was no rise in pulmonary artery diastolic pressure. Pain was usually a late feature. Silent ST segment elevation occurred at rest and pulmonary artery diastolic pressure increased in all but one episode. Silent exertional ST segment depression was associated with a greater increase in pulmonary artery diastolic pressure than that seen during ST segment elevation. ST segment depression preceded or followed ST segment elevation in two episodes. The onset of ST segment elevation nearly always preceded the onset of a rise in pulmonary artery diastolic pressure. Ergometrine maleate provocation produced a rise in pulmonary artery diastolic pressure in three patients. In one there was no response to 1000 micrograms but spontaneous episodes of ST segment elevation were recorded during ambulatory monitoring. Treadmill exercise resulted in both ST segment elevation and depression with a similar haemodynamic response during both types of electrocardiographic change. When there is important coronary artery disease in two or more vessels ST segment changes may occur in different territories during treadmill exercise and during spontaneous episodes. Ambulatory pulmonary artery diastolic pressure monitoring is a useful technique for the investigation of variant angina.

The incidence of coronary artery spasm at the site of previous successful angioplasty and its importance in leading to subsequent restenosis or recurrence of symptoms are unknown. Fourteen consecutive patients with single vessel coronary artery disease who had undergone successful percutaneous transluminal angioplasty were studied. All patients were given ergometrine maleate (ergonovine maleate) intravenously during repeat cardiac catheterisation six weeks to three months after angioplasty. Five patients demonstrated excessive luminal reduction (spasm) at the site of previous angioplasty that led to luminal stenoses ranging from 50% to 79%. Two of these patients developed chest pain and ST segment changes during ergometrine maleate provocation and they also showed maximal vasoconstriction. The remaining nine patients did not develop important luminal change at the site of angioplasty after ergometrine maleate. Ergometrine maleate administration resulted in less than or equal to 20% reduction in lumen diameter of adjacent apparently normal sections of the coronary arteries in all but two patients. At the site of previous angioplasty in the five patients with spasm, however, the lumen was constricted by a mean (SD) of 51 (12)%, whereas in the nine patients not demonstrating spasm mean reduction was 12 (7)%. Thus hypersensitivity to ergometrine maleate at the site of previous successful angioplasty was demonstrated in over a third of consecutive patients with single vessel coronary artery disease. The importance of this finding to long term results of coronary angioplasty needs to be investigated further.

A 32-year-old White man suffered a large transmural inferoposterior myocardial infarction (MI). Coronary vasospasm is strongly suspected of having caused this MI since the ergometrine maleate provocation test gave rise to severe coronary vasospasm resulting in total occlusion of the dominant right coronary artery, without angina or ECG or haemodynamic features of myocardial ischaemia. This is a most unusual response to ergometrine maleate. Possible explanations are suggested and the implications are briefly discussed.