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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.

A study of 68 patients showed that the ergometrine test is a rather informative method of the diagnosis of ischemic heart disease that supplements essentially the results of loading tests. The authors demonstrate the possibility of using the ergometrine test with the purpose of evaluating the effect of antianginal therapy.

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)

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.

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.

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.

In 17 anginal patients with critical narrowing of the left anterior descending artery, we studied the effects of acute ischemia, either induced by atrial pacing or by ergonovine, on transmyocardial platelet behavior. Six other patients with atypical chest pain and normal coronary arteries served as controls. Simultaneous arterial and great cardiac vein samples were drawn during control and ischemia to measure the levels of platelet factor four (PF4) and beta-thromboglobulin (BTG). During pacing-induced ischemia the great cardiac vein-arterial differences of PF4 and BTG decreased significantly, indicating a reduced platelet aggregability; no significant changes were observed in the control patients. By contrast, when ischemia resulted from ergonovine-induced spasm of the left anterior descending artery (five patients), the great cardiac vein-arterial differences increased, indicating enhanced platelet aggregability. Again no differences were observed in the patients with a negative ergonovine test. The results of our study suggest that the transcardiac platelet behavior may vary during different ischemic conditions. When ischemia is due to increased myocardial demands and flow is normal or increased, myocardial metabolites released from the ischemic area may oppose platelet aggregation. By contrast, spasm and the stagnant flow resulting from it may enhance platelet aggregation.

Thirty-six consecutive patients with evolving acute myocardial infarction underwent emergent coronary angiography and intracoronary thrombolysis with urokinase. Nineteen of the patients had had angina before the infarction (group A), whereas the infarction was unheralded in the remaining 17 (group B). Thirty-two vessels (88%) were patent at follow-up angiography performed after 3 to 4 weeks, and the residual stenosis was 87% +/- 14% in group A and 47% +/- 25% in group B (p less than 0.001). Coronary spasm was provoked by ergonovine maleate in four of 12 patients in group A (33%) and in three patients in group B (18%). Coronary revascularization was undertaken in nine patients in group A and three in group B. These results indicate that patients with angina preceding acute myocardial infarction are more likely to have significant stenosis even at the late follow-up stage and to have a more urgent need for subsequent coronary revascularization. It also seems apparent that thromboembolism in most patients and coronary spasm in a few patients without significant coronary narrowing play significant causal roles in the onset of acute myocardial infarction.

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.

In 6 patients affected by spontaneous angina with S-T elevation and coronariographic findings of obstruction, intravenous administration of ergonovine maleate determined the same clinical and ECG patterns of spontaneous episodes. The coronary arteriography during pain showed a marked spasm with occlusion of a large coronary vessel in four patients. In 2 patients with atypical chest pain and normal coronariogram, E.M. did not induce pain, ECG abnormality or coronariographic alterations. The role of spasm in spontaneous angina is discussed.

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.

It is widely accepted that the occurrence of chest pain and/or ST segment elevation during ergonovine testing is a hallmark of abnormal coronary constriction. However, the negativity of this test cannot be considered as an incontrovertible proof of the absence of coronary sensitivity to vasoconstriction. Indeed, it could only indicate that the resulting effect is inadequate to critically reduce coronary blood flow. To test this hypothesis we studied 12 patients with proven coronary artery disease and negative ergonovine test who had complained of chronic exertional angina pectoris and referred variable threshold for the occurrence of pain. They were submitted to atrial pacing (starting from 90 bpm, with 10 bpm increments every 2 min) before (control) and after ergonovine administration (total dose = 0.675 mg). Time, heart rate and rate pressure product were evaluated at the onset of angina and significant ischemia (0.1 mV ST segment depression). After ergonovine, angina was achieved earlier (405 +/- 173 vs 526 +/- 180 sec, p less than 0.005) than during control and at a lower heart rate (116 +/- 15 vs 131 +/- 15 bpm, p less than 0.001) and rate pressure product (15.8 +/- 2.0 vs 18.8 +/- 2.3 X 10(3) U, p less than 0.001). Changes in anginal threshold were widely variable among cases being that the time to onset of pain was dramatically reduced in certain patients but unchanged in one. Similar results were obtained when substituting the ischemic to the anginal threshold. Thus, negativity to ergonovine testing does not imply the absence of coronary constriction which may be revealed when increasing myocardial oxygen demand by atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

In some patients with stable angina, the variability of results during repeated exercise tests is higher than in others with similar symptoms. The aim of the study was to assess whether this difference can be explained by a different susceptibility of the coronary arteries to vasoconstrictor stimuli. Ten patients (group A) with stable angina, who developed myocardial ischemia (angina and ST segment depression greater than 0.1 mV) following ergonovine-induced coronary constriction, and 10 other patients (group B) with stable angina, but a negative ergonovine test result, were subjected to two treadmill exercise tests. The variability of heart rate and heart rate-blood pressure product at 0.1 mV ST segment depression was significantly higher in group A than in group B (12 +/- 4 vs 4 +/- 4 bpm, respectively, p less than 0.001 and 3366 +/- 1900 vs 930 +/- 960 bpm X mm Hg, respectively, p less than 0.005), such as the variability of heart rate-blood pressure product at the onset of angina (3887 +/- 2400 vs 1428 +/- 1800 bpm X mm Hg, respectively, p less than 0.04). The remaining exercise parameters were always more variable in group A than in group B, but these differences did not achieve statistical significance. Thus patients with stable angina who develop myocardial ischemia in response to ergonovine have a larger variability of results during repeat exercise testing. Such findings could be explained by an enhanced susceptibility to the coronary constrictor effects of exercise resulting in dynamic changes in coronary flow reserve.

Coronary angiography was performed during 34 angina attacks in thirty patients admitted because of recurrent angina at rest. Nineteen (seventeen with S-T segment elevation and two S-T depression) had angiograms during a spontaneous attack, eleven (nine with S-T elevation and two with S-T depression) during an attack induced by intravenous ergonovine maleate. Control coronary angiograms showed a wide range of atherosclerotic obstruction, from normal vessels to severe triple-vessel disease. During the anginal attack, all patients with S-T segment elevation had vasospasm localised to one of the major branches, often resulting in complete occlusion. Attacks with S-T segment depression were seen only in patients with double or triple vessel disease, and here the vasospasm generally affected coronary branches without causing complete occlusion. When appropriately searched for, vasospastic angina seems to be common.

We performed coronary angiography and ergonovine maleate provocative tests (EM test) for 3,000 consecutive patients to clarify 1) the incidence of coronary arterial spasm and significant fixed organic stenosis in ischemic and non-ischemic heart diseases, and 2) the relation of these angina-inducing mechanism(s) to rest (R), effort and rest (E & R), and effort (E) angina. Coronary arterial spasm was defined as total or subtotal occlusion induced by ergonovine test, and fixed stenosis was defined as stenosis with more than 70% narrowing of luminal diameter measured after administration of isosorbide dinitrate. Subjects consisted of 3,000 consecutive patients and were categorized in four groups including 1,145 patients who had typical angina pectoris (Group I: rest angina 653, effort angina 230, and combined rest and effort angina 262), 398 patients with myocardial infarction (Group II), 648 patients with atypical chest pain (Group III), and 809 patients who eventually had diagnostic catheterization for heart diseases other than of ischemic nature (Group IV). Results were as follows: 1. The incidence of coronary artery spasm was 22.2% in Group I, 22.9% in Group II, 1.2% in Group III, and 3.7% in Group IV. 2. In Group I, there was a close relationship between the mechanism of angina and the type of occurrence of typical chest pain; coronary artery spasm was more likely observed in rest angina, organic stenosis was observed in effort angina, and the combined type was observed in cases with both spasm and organic stenosis. Furthermore, the occurrence of coronary artery spasm was significantly more frequent in cases with single vessel disease compared with those with multivessel disease (50.7% vs. 26.7%, p less than 0.005). 3. In Group II, the most frequent angiographic evidence was fixed organic stenosis, and there was no relationship between spasm and the numbers of diseased vessels. 4. In Groups III and IV, the most common entity causing coronary artery spasm was hypertrophic cardiomyopathy. In conclusion, two major mechanisms of angina pectoris, i.e., coronary artery spasm and organic stenosis, are closely related to the symptomatology of this disease, such as rest, effort and combined rest and effort types.