Synthesis of M + 4 Stable Isotopomers of Ergometrine and Ergometrinine.

The priority ergot alkaloids ergometrine and ergometrinine are highly toxic mycotoxins naturally occurring in different types of grains (i.e. rye, wheat, rice), as well as grain-based foods and, therefore, have gained increasing importance for food safety over the last years. The application of HPLC-MS/MS for the analysis of ergot alkaloids in food presupposes the availability of isotopically labelled internal standards. Thus, a multistep synthesis was developed for ergometrine-(N-13CD3) and its epimer ergometrinine-(N-13CD3) with a mass shift of four units compared with the parent compounds. The synthesis is based on the preparation of stable isotope labelled lysergic acid that was coupled with (S)-alaninol. The chemical synthesis of both compounds has been achieved in six steps with an overall yield of 1 % (ergometrine-(N-13CD3)) and 0.6 % (ergometrinine-(N-13CD3)), respectively. Structural identification was performed by MS analysis as well as 1H and 13C NMR.

Ergonovine maleate testing during cardiac catheterization: a 10-year perspective in 3,447 patients without significant coronary artery disease or Prinzmetal's variant angina.

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.

Intravascular ultrasound detection of atherosclerosis at the site of focal vasospasm in angiographically normal or minimally narrowed coronary segments.

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.

Increased echodensity of transiently asynergic myocardium in humans: a novel echocardiographic sign of myocardial ischemia.

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.

Quantitative arteriographic responses to ergonovine provocation in subjects with atypical chest pain.

To evaluate the nonspecific vasoconstrictor response to intravenous ergonovine, and identify patient-related factors that systematically alter changes in coronary dimensions, 33 subjects (22 women, 11 men), mean age 54 years (range 39 to 70) were studied using a standardized ergonovine provocation test (Stanford protocol). Clinical responses, systemic hemodynamics and electrocardiographic changes were determined, with quantitative arteriography used for sequential measurement of proximal right coronary dimensions. A progressive decrease in proximal right coronary diameter was observed, with average control values and final diameters equaling 3.25 +/- 0.49 and 2.56 +/- 0.49 mm, respectively, thus representing an overall -21.2% change from baseline. No significant differences existed in control dimensions when analyzed with respect to gender (3.20 +/- 0.59 vs 3.40 +/- 0.72 mm, women vs men, difference not significant), although women demonstrated a greater decrease from baseline values (0.80 +/- 0.30 vs 0.50 +/- 0.24 mm, women vs men, p less than 0.05). The presence of minor atherosclerotic disease, as determined by the presence of minor (less than 30% diameter) luminal irregularities within the right coronary artery, failed to alter control dimensions (3.30 +/- 0.48 vs 3.20 +/- 0.51 mm, normal vs atherosclerotic persons, difference not significant), but was associated with more ergonovine-induced coronary vasospasm (0.41 +/- 0.27 vs 0.84 +/- 0.21 mm, normal vs atherosclerotic persons, p less than 0.01). Therefore, sequential intravenous ergonovine maleate infusion resulted in progressive, nonspecific reductions in proximal right coronary artery dimensions in subjects without a history compatible with vasospastic angina. This nonspecific vasoconstrictor effect was accentuated in women and subjects with intimal irregularities suggestive of minor atherosclerotic coronary disease.

Comparative effects of oral molsidomine and nifedipine on methylergometrine-induced coronary artery spasm.

Twelve consecutive patients (10 men and 2 women, mean +/- standard deviation age 49 +/- 9 years) with chest pain, angiographically normal coronary arteries and coronary artery spasm documented by methylergometrine testing received a single oral dose of molsidomine (4 mg) or nifedipine (10 mg) in a randomized, double-blind, crossover fashion at a 24-hour interval. Coronary artery spasm was documented during coronary angiography in 6 patients (left anterior descending artery, 3; right coronary artery, 2; left circumflex, 1). In the remaining 6 patients, coronary artery spasm was documented by a positive methylergometrine test performed at the bedside, which provoked ST-segment elevation in the inferior (n = 3), anterior (n = 1) or lateral (n = 2) leads. Ninety minutes after administration of the study medication, methylergometrine testing was performed at the bedside, using incremental doses of up to 0.4 mg of methylergometrine. After molsidomine, 10 patients (83%) had a negative and 2 had a positive test; after nifedipine, 9 patients (75%) had a negative and 3 a positive test. Only 1 patient had a methylergometrine test that remained positive after either molsidomine or nifedipine. Therefore, molsidomine appears as effective as nifedipine in suppressing methylergometrine-induced coronary artery spasm in patients with variant angina. In addition, patients not responding to 1 of the study medications may respond to the other.

Usefulness of a high-dose dipyridamole-echocardiography test for diagnosis of syndrome X.

This study assesses whether the high-dose dipyridamole-echocardiography test (DET, 2-D echocardiographic and 12-lead electrocardiographic monitoring during dipyridamole infusion, up to 0.84 mg/kg over 10 minutes) can help to identify patients with syndrome X. DET was performed in 10 control subjects (group A) and in 19 patients with syndrome X (group B). Patients in group B had chest pain on effort, a positive exercise stress response (more than 0.1 mV of ST-segment depression), negative ergonovine test response and normal left ventricular function and coronary angiographic findings. During DET no subject in group A showed transient asynergy or ST-segment depression and none had chest pain; in group B, no patient had transient asynergy, 13 (68%) had chest pain and 16 (84%) had more than 0.1 mV of ST-segment depression. Percent fractional shortening was not significantly different in the 2 study groups, either basally (group A, 35 +/- 7; group B, 37 +/- 8) or at peak hyperkinesia during DET (group A, 48 +/- 8; group B, 54 +/- 10). Thus, dipyridamole-induced chest pain and ST-segment depression in patients with syndrome X are not associated with impaired regional or global left ventricular function. This entity of echocardiographically silent myocardial ischemia during DET may be a clue to noninvasive detection of syndrome X.

Reactivity of proximal and distal angiographically normal and stenotic coronary segments in chronic stable angina pectoris.

To assess whether vasoreactivity of significant coronary stenosis (greater than 50% intraluminal diameter reduction) and that of angiographically normal coronary segments differs in proximal and distal locations, 53 patients (40 men, 13 women, mean +/- standard deviation age 55 +/- 11 years) with chronic stable angina and angiographically documented coronary artery disease were studied. While abstaining from antianginal therapy, all 53 patients underwent coronary arteriography before and after 1 mg of intracoronary isosorbide dinitrate and 21 of the 53 also before and after 20 to 30 micrograms intracoronary ergonovine. Computerized quantitative angiography was used to assess changes in the intraluminal diameter of 126 normal coronary segments (63 proximal, 63 distal) and 43 significant coronary stenoses. Nitrates dilated proximal normal coronary segments by 7.4 +/- 1.2% and distal normal coronary segments by 15 +/- 1.7% (p less than 0.01). Significant proximal coronary stenoses dilated by 11 +/- 2.5% and distal stenoses by 23 +/- 2.8% (p less than 0.01) after nitrates. Ergonovine reduced the diameter of proximal normal coronary segments by 9.3 +/- 1.7% and that of normal distal segments by 15.5 +/- 1.4% (p less than 0.01). Proximal stenoses constricted by 11 +/- 2.2% and distal stenoses by 18.4 +/- 2.8% (p = 0.06). Analysis of segments showed that nitrates dilated 19 of 63 (30%) proximal normal segments by (greater than or equal to 10%), 31 of 63 (49%) distal (p less than 0.05) and 21 of 43 (49%) stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Relative roles of preload increase and coronary constriction in ergonovine-induced myocardial ischemia in stable angina pectoris.

To assess the relative role of increased ventricular preload and critical coronary lesions in ergonovine-induced myocardial ischemia, 9 normal subjects (group A), 7 patients with stable angina (group B) and 5 with variant angina (group C) were studied. In all patients, the 12-lead electrocardiogram, blood pressure and left ventricular (LV) volume (technetium-99m blood pool) were continuously recorded before and during administration of incremental doses of ergonovine given at 5-minute intervals. In all subjects, an initial LV dilatation developed; in group B and C patients, this was followed by a decrease in stroke volume and ejection fraction with subsequent onset of electrocardiographic changes and angina. The interval between these events was significantly shorter in group C and in 3 group B patients; in these patients, signs of ischemia appeared with smaller ergonovine doses and at minimal preload increase, coronary constriction being the likely mechanism of ischemia. In the remaining 4 group B patients, the onset of stroke volume, ejection fraction, electrocardiographic changes and angina was significantly delayed, occurring after administration of larger ergonovine doses when LV volume was already considerably increased. This finding suggests that the loading effect of ergonovine on LV volume, rather than on coronary constriction, could be the prevailing mechanism of ergonovine-induced ischemia in these patients.

Perioperative coronary arterial spasm: long-term follow-up.

Six patients who survived episodes of coronary arterial spasm occurring immediately after coronary bypass grafting were followed up for 15 to 30 (mean 20) months after operation. In all patients coronary spasm occurred in an unobstructed dominant right coronary artery and caused inferior transmural ischemia. Sudden circulatory collapse occurred in five of the six patients as a consequence of acute coronary spasm. All patients were treated with nitroglycerin followed by nifedipine. No patient has had recurrent angina or other evidence of spontaneous coronary spasm since surgery. Cardiac catheterization studies, including ergonovine maleate testing, were repeated 3 to 12 months after surgery in five of the six patients. The right coronary artery and all bypass grafts were patent in all five. Four patients had new inferior wall motion abnormalities. Ergonovine provoked focal right coronary arterial spasm in one patient. It is concluded that manifestations of coronary spasm after myocardial revascularization range from asymptomatic S-T segment elevation to severe hypotension. These episodes of perioperative spasm may cause myocardial necrosis. Coronary spasm has not recurred in patients who survived perioperative spasm, but some patients may have a continued predisposition to development of coronary spasm late after surgery.

Acute myocardial infarction associated with systemic lupus erythematosus documented by coronary arteriograms.

A 19-year-old man with untreated systemic lupus erythematosus had an acute myocardial infarction. A coronary arteriogram five hours after the onset of symptoms revealed total occlusion of the left anterior descending coronary artery. Reperfusion was achieved by coronary thrombolytic therapy with urokinase. Four weeks later, a coronary arteriogram showed only minimal luminal irregularities at the original site of occlusion, where significant reduction in diameter could be induced by ergonovine maleate. This case suggests that coronary arterial involvement in systemic lupus erythematosus may be related to coronary arterial spasm.

Effect of ergonovine on prolactin secretion and milk let-down.

The effect of ergonovine maleate on prolactin secretion and lactation was determined in 10 puerperal women. Serum prolactin concentration measured by radioimmunoassay resulted in 537.2 +/- 45.9 ng/ml (M +/- SE) before the oral administration of 0.6 mg ergonovine maleate, and 89.7 +/- 25.6 ng/ml after 7 days of therapy. The serum prolactin concentration seen in the control group of nonlactating women (562.0 +/- 36.1 and 218.0 +/- 27.3 ng/ml) was significantly greater than (P less than 0.01) that seen in the treated group. In 2 additional patients it was also demonstrated that the simultaneous administration of ergonovine by oral and intravenous routes potentiates the suppressive effect on prolactin secretion. Three of the 10 treated women showed progressive inhibition of lactation. This study shows that ergonovine maleate interferes with prolactin secretion, and may decrease milk production.

Values of intravenous ergonovine test with two-dimensional echocardiography for diagnosis of coronary artery spasm.

The purpose of this study was to evaluate the clinical validity of the bedside ergonovine test with digital echocardiography and the side-by-side continuous cineloop display method (ergonovine echocardiography) as a noninvasive diagnostic tool for coronary artery spasm. Bedside ergonovine test was performed in 66 patients who showed coronary vasospasm during coronary angiography including provocation testing (group with variant angina) and 39 patients with normal angiograms and no evidence of coronary artery spasm (group with nonanginal pain). A bolus of ergonovine maleate (0.025 or 0.05 mg) was injected at 5-minute intervals up to total cumulative dosage of 0.35 mg, and 12-lead electrocardiography and two-dimensional echocardiography were recorded every 3 minutes after each injection. Left ventricular wall motion was analyzed with a commercially available quad system. The positive criteria of bedside ergonovine test included reversible ST segment elevation or depression on electrocardiograms (ECG criteria) and reversible regional wall motion abnormalities by echocardiography (Echo criteria). The overall sensitivity and specificity of ECG criteria were 53% (35/66; 95% confidence interval 41% to 65%) and 100%, respectively. By Echo criteria the sensitivity increased to 89% (59/66; 95% confidence interval 81% to 97%), with a specificity of 95% (37/39).(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of spontaneous and provoked coronary spasms after percutaneous transluminal coronary angioplasty.

We studied the incidence of spontaneous and ergonovine-induced coronary arterial spasm during repeat coronary angiography in 96 consecutive patients with single-vessel disease who had undergone successful angioplasty. Follow-up angiography was performed after a mean of 6 months (1-8 months). Sixty patients demonstrated no restenosis and in 36 patients restenosis (greater than 50% restenosis) occurred. Spasms of the arteries at the site of dilatation were significantly (P less than 0.001) more frequent in patients with restenosis (18/36; 50%) than in patients without restenosis (4/60; 7%). Before angioplasty, no differences were found in the clinical characteristics between the two groups. Likewise, the morphologic results of angioplasty were identical. Despite long-term treatment with nifedipine (30-60 mg daily) and aspirin (0.5 g daily), 14 of 18 patients with restenosis and coronary spasm suffered from spontaneous angina, as compared to only 3 of 18 patients with restenosis without demonstrable spasm. Three of the 4 patients without restenosis but with detectable spasm were also symptomatic. Thus our findings suggest that spasm of the coronary arteries achieves some importance as a pathophysiological factor for recurrence following coronary angioplasty.

Beta-thromboglobulin release within coronary circulation--a potential role of platelets in ergonovine-induced coronary vasospasm.

The role of platelets in the pathogenesis of acute myocardial ischemia is not yet agreed upon. In this study, the gradient of plasma beta-thromboglobulin concentration between coronary sinus and aorta was used as an indicator of platelet activation within the coronary circulation. Blood samples were drawn before and after injection of ergonovine maleate in patients without fixed coronary stenosis in whom significant coronary spasm was induced by ergonovine (n = 8, Group 1), patients with significant stenosis (greater than or equal to 75%) of the left anterior descending artery and positive ergonovine test (n = 7, Group 2) and patients with significant stenosis of left anterior descending coronary artery and negative ergonovine test (n = 11, Group 3). Fifteen patients with normal coronary arteries who were negative in the ergonovine test served as controls (Group 4). After the ergonovine test, all Group 1 patients revealed a significant increase of beta-thromboglobulin gradient (P less than 0.001), while those in other groups did not. Additionally, the gradient after the ergonovine test of Group 1 patients was larger than those of the other groups (P less than 0.01). All blood samples after the ergonovine test were collected before or at the onset of angina attacks. These results suggest that platelet activation within the coronary circulation has some pathogenic role, probably as an aggravating factor, in coronary artery spasm.

Long-term follow-up of coronary narrowing with spasm.

In order to clarify the fate of coronary narrowing with spasm, repeat angiograms of coronary narrowing with and without spasm were compared. The mean interval between the first and second angiograms was 3.6 years (range, 1.1-8.5 years). Improvement of narrowing was more frequent in the vasospastic group (23%) than in the group without spasm (3%, P < 0.005). The cause of this improvement in the vasospastic group may have been the resolution of the spasm in the first angiogram, but the presence of intravascular thrombus or bleeding or edema of the coronary arterial wall may have resolved in the second angiogram.

Subacute toxicity of ergometrine maleate in rats.

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.

Superior mesenteric artery vasoactivity in hyperlipidemic Watanabe rabbits versus normal lipidemic New Zealand controls.

Recent in vitro studies on isolated coronary and mesenteric arteries have shown that hyperlipidemia appears to hypersensitize the vascular arterial smooth muscle to drugs such as ergonovine and that this increased contractility seems to be mediated by a serotinergic mechanism. This results in vasospasm with exposure to certain vasoactive drugs such as serotonin or norepinephrine. However, in vivo quantification of this observed phenomenon has not been done. In the present study we used Watanabe hereditary hyperlipidemic (WHHL) rabbits (cholesterol level 459 +/- 216 mg/dL) and the normal lipidemic New Zealand white (NZW) rabbit (cholesterol level 35 +/- 19) as a control in the study of hyperlipidemia and blood flow changes in response to various vasoactive drugs. Blood flow measurements were made by the video dilution technique (VDT) following catheterization of the superior mesenteric artery. The serotinergic vasoactive drug ergonovine maleate was injected into the superior mesenteric artery at low dose (0.002) mg/kg) and high dose (0.004 mg/kg). A significant decrease (p less than .05) in blood flow was observed in response to high-dose ergonovine maleate in WHHL rabbits compared to the NZW rabbits. This in vivo experiment confirms the in vitro studies showing that hyperlipidemia sensitizes mesenteric arteries in the presence of serotinergic stimuli. The vasodilators verapamil hydrochloride and calcitonin gene-related peptide (CGRP) injected into the superior mesenteric artery caused a marked increase in flow in both the WHHL and the normal lipidemic NZW rabbits. This model can be used in the assessment of superior mesenteric artery ischemia and its reversal.

Ergonovine maleate test detects anginal patients with poorly reproducible exercise tests.

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.

Impaired left ventricular filling during ST-segment depression provoked by dipyridamole infusion in patients with syndrome X.

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.