Effect of magnesium on anginal attack induced by hyperventilation in patients with variant angina

To examine whether or not magnesium suppresses coronary spasm, the effect of magnesium infusion on anginal attacks induced by hyperventilation was studied in 20 patients with variant angina. In all patients, anginal attacks associated with ischemic ST segment changes on the electrocardiogram were repeatedly induced by hyperventilation. The study was performed in the early morning successively for 3 days. On days 1 and 3 (control studies), 50 minutes before the hyperventilation test, a 5% glucose solution was infused as a placebo. On day 2 (magnesium study), 50 minutes before the hyperventilation test, magnesium sulfate (0.27 mM/kg body wt) was infused during a 20-minute period. During the control studies, anginal attack was induced by hyperventilation in all 20 patients, whereas during the magnesium study, anginal attack was induced by hyperventilation in only six (30%) of the 20 patients (p less than 0.001 vs. control studies). The changes in arterial blood pH and PCO2 caused by hyperventilation were not significant between the control study and the magnesium study. Mean serum magnesium concentration increased from 2.2 +/- 0.2 to 6.0 +/- 0.5 mg/dl immediately after infusing magnesium and was 4.5 +/- 0.6 mg/dl before the hyperventilation test during the magnesium study. We conclude that magnesium suppresses anginal attacks induced by hyperventilation in patients with variant angina.     

Exercise-induced angina provoked by aspirin administration in patients with variant angina

The effects of aspirin (4.0 g/day) given orally to eight patients with variant angina were observed. An exercise stress test performed in the morning was positive in two of seven patients during placebo administration, whereas a test performed in the afternoon at the same exercise work load resulted in negative findings. During aspirin administration, the afternoon exercise test repeatedly provoked anginal attacks associated with electrocardiographic changes (S-T segment elevation in five and S-T depression in two). Rate-pressure product at the end of the exercise test during aspirin administration was significantly lower than that during placebo administration (p <0.01). During aspirin administration, the frequency of angina increased markedly, and the attacks occurred not only during the night or early morning but also in the daytime in six of the eight patients. Our observations suggest that aspirin, in this large dose, reduces the capacity for exercise and provokes exercise-induced coronary arterial spasm in patients with variant angina.     

Coronary arterial spasm as a cause of exercise-induced ST-segment elevation in patients with variant angina.

Four patients with variant angina pectoris exhibited reproducible exercise-induced chest pain and ST-segment elevation. Coronary arterial spasm was documented with arteriography during exercise-induced ST-segment elevation (three patients) or after intravenous administration of ergonovine maleate (one patient). Our observations show that in patients with variant angina exercise can trigger coronary arterial spasm, thus inducing anginal pain and ST-segment elevation.     

Coronary arteriography and left ventriculography during spontaneous and exercise-induced ST segment elevation in patients with variant angina

The present study is an angiographic demonstration of coronary artery spasm during both spontaneous and exercise-induced angina in three patients with variant angina. In each case, clinical, ECG, coronary angiographic, and left ventriculographic observations were made at rest, during spontaneous angina, and during exercise-induced angina. The character of chest pain was similar during spontaneous and exercise-induced episodes. ST segment elevation was present in the anterior ECG leads during both episodes. The left anterior descending coronary artery became partially or totally obstructed during both types of attacks. When coronary spasm was demonstrated during both types of attacks, left ventriculography disclosed akinetic or dyskinetic wall motion in the area supplied by the involved artery. In those patients with reproducible exercise-induced ST segment elevation and chest pain, thallium-201 scintigraphy showed areas of reversible anteroseptal hypoperfusion. Thus in selected patients exercise-induced attacks of angina were similar to spontaneous episodes.     

Myocardial infarction after exercise-induced electrocardiographic changes in a patient with variant angina pectoris

The electrocardiographic response to stress testing varies considerably in patients with variant angina pectoris: no change in the S-T segment as well as S-T segment depression and elevation have been observed. This report describes a patient with a resting ST-T abnormality that reverted to normal appearance with exercise. However, the patient experienced severe chest pain shortly after discontinuing exercise testing, and an electrocardiogram showed evidence of acute anterolateral infarction. The possible implications of such electrocardiographic changes are discussed.     

The relation of physical and mental stress to magnesium deficiency in patients with variant angina]

In this study we assessed the role of psychological factor in the etiology of coronary vasospasm using the Cornell Medical Index (CMI), focusing attention on the relationship between stress and serum magnesium (Mg). The study subjects consisted of 25 patients with variant angina (VA), 32 with old myocardial infarction without vasospasm (OMI), and 34 healthy men (controls). On a neurosis-discriminative diagram of CMI, areas I and II were considered as normal and areas III and IV were considered to be a neurotic disorder. The stress test included exercise and a quiz. Exercise test was performed in 8 patients with VA, 6 with OMI, and 5 controls, and a quiz was given to 4 patients with VA. Plasma catecholamines [noradrenaline (NA), adrenaline (Ad), dopamine], aldosterone, adrenocorticotropic hormone (ACTH) and serum electrolytes (Mg, Ca, Na, K, Cl) were measured before and after exposures to stress. The following results were obtained: 1) Of the patients with VA, 40.0% were categorized as area III or IV, compared to 18.7% of the patients with OMI, and 2.9% of the control subjects. 2) Among patients with VA, 64.0% exhibited anxiety states compatible with a psychological disorder. 3) NA and Ad were increased after exercise stress. 4) Serum Mg and Ca were also increased after exposure to exercise stress in all groups, and the degrees of these changes were correlated to the exercise intensity. The %delta Mg/%delta NA ratio, a parameter of the effect of catecholamine on the serum Mg, was greater in patients with VA than in those with OMI and the controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anti-ischemic effects of celiprolol in patients with exercise-induced angina pectoris

The anti-ischemic properties of the new cardioselective beta-adrenoreceptor antagonist celiprolol were investigated in an open study of 12 men (mean age: 58 +/- 6.6 years) with exercise-induced angina pectoris. After all previous anti-anginal medication had been withdrawn for at least 5 half-lives, the patients received placebo, single doses of nitroglycerin buccal spray, sublingual nifedipine, celiprolol alone, and then in association with nitroglycerin and nifedipine. Exercise tests were performed on a bicycle ergometer, with continuous electrocardiographic monitoring. Significantly more work was completed after treatment with celiprolol than at baseline (5280 +/- 2500 versus 4005 +/- 1792 kpm; P less than 0.01). There were further improvements in work completed after the addition of nitroglycerin and nifedipine. Celiprolol reduced the mean resting heart rate from a baseline value of 77.1 beats/min to 69.2 beats/min (P less than 0.01). In contrast, nifedipine induced tachycardia (82.6 beats/min). At rest, all treatments significantly reduced systolic blood pressure, but only nifedipine significantly reduced diastolic blood pressure. At the completion of the exercise protocol, celiprolol reduced the maximal systolic and diastolic blood pressure (P less than 0.05) with further decreases after the addition of nifedipine. The double product was significantly decreased by celiprolol compared with control, nitroglycerin and nifedipine. There was a further improvement of the double product after the addition of nitroglycerin to celiprolol, but the further increase after addition of nifedipine was not significant. In conclusion, it is clear that celiprolol, both alone and in combination with nitroglycerin or nifedipine, can significantly increase the work capacity of patients with exercise-induced angina pectoris and significantly reduce myocardial oxygen consumption.     

Circadian variation of exercise capacity in patients with Prinzmetal's variant angina: role of exercise-induced coronary arterial spasm.

Thirteen patients with Prinzmetal's variant angina performed treadmill exercise tests in the early morning and in the afternoon of the same day. The attacks with ST elevation were induced repeatedly in all 13 patients in the early morning, but in only two patients in the afternoon. Propranolol did not suppress the exercise-induced attacks in all 13 patients. Diltiazem suppressed the attacks in all 13 patients and phentolamine in eight of the nine patients. Coronary arteriograms demonstrated that spasm occluding completely or almost completely the large coronary artery supplying the area of myocardium showing ST elevation appeared during the attacks and disappeared along with the attacks after nitroglycerin administration in all four patients in whom the attacks were induced by arm exercise in the catheterization laboratory. We conclude that there is circadian variation of exercise capacity in patients with Prinzmetal's variant angina caused by coronary arterial spasm induced by exercise in the early morning but not in the afternoon.     

Long-term prognosis of patients with variant angina

The long-term prognosis of variant angina and the factors influencing it were assessed in 217 consecutive patients hospitalized in our coronary care unit and followed for a mean of 65 months (range 2 to 123). Cardiac death occurred in 30 patients and an additional 54 experienced a nonfatal myocardial infarction. Survival at 1 and 5 years was 95% and 89%, respectively; survival without infarction was 83% and 69%. Coronary disease and the degree of disease activity were strong predictors of survival by Cox analysis. Survival at 1 year was 99%, and that at 5 years was 95% and 94%, respectively, for patients with one-vessel disease (n = 81) and for those without stenoses of 70% or greater (n = 87). Survival at 1 and 5 years was only 87% and 77% for those with multivessel disease (n = 40). The Cox analysis selected left ventricular function, initial treatment, extent score, duration of angina at rest, and disease activity as multivariate predictors of survival without infarction. Coronary disease was a strong predictor (p less than .0001) of survival without infarction by univariate analysis. Treatment with nifedipine, diltiazem, or verapamil improved survival without infarction compared with other medical treatment (p = .002). Myocardial infarction occurred most commonly soon after diagnosis in patients with a short history of angina at rest. Late coronary events were almost never preceded by resting angina.     

Circulating T-lymphocyte activation in patients with variant angina

BACKGROUND: Both experimental and pathological studies suggest that immune response and inflammation may play an important role in the pathogenesis of coronary spasm. DESIGN: To elucidate the role of systemic immune and inflammatory responses in the pathogenesis of coronary spasm, we studied circulating T-lymphocyte activation in variant angina patients (VAPs), stable effort angina patients (EAPs) and in control participants. METHODS: Twenty documented VAPs, 13 EAPs and 20 control participants were studied. To evaluate T-lymphocyte activation, T-lymphocyte surface antigen expression, including CD3, CD4, CD8 and HLA-DR, was measured by two-colour flow cytometric analysis. Serum-soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) were also measured by enzyme-linked immunosorbent assay. We restudied 10 of the VAPs to investigate the relationship between the disease activity of variant angina and T-lymphocyte activation. RESULTS: The percentage of CD3+/DR+ T-lymphocytes in VAPs (14.8%) was significantly higher than in EAPs (10.7%, P < 0.05) and control participants (9.7%, P < 0.005); however, levels of sIL-2R were the same among the three groups. Levels of CRP were within normal range in all VAPs. The percentage of CD8+/DR+ T-lymphocytes was significantly higher in VAPs (9.5%, P < 0.005) than in EAPs (5.5%) and control participants (5.9%), whereas the percentage of CD4+/DR+ T-lymphocytes was similar among the three groups. The percentage of activated T-lymphocytes in VAPs was unchanged during the follow-up period (mean intervals, 10 months). CONCLUSIONS: These results indicate that the chronic activation of T-lymphocytes, especially CD8+ T-lymphocytes, may be involved in the pathogenesis of coronary spasm.     

Silent myocardial ischemia in patients with variant angina

Twenty-four hour ambulatory electrocardiographic recording was performed in 56 patients with variant angina admitted to the coronary care unit in order to evaluate the incidence and pathophysiology of silent episodes of ST elevation. Of 696 episodes of ST elevation of more than 0.1 mV identified during a recording period of 141 days, 531 (76%) episodes were completely silent. The incidence of silent episodes increased as the number of total ischemic episodes per day increased. Silent ST elevation revealed a significantly shorter duration and a lower intensity than symptomatic ST elevation. However, there were wide overlaps in the duration and intensity of ST elevation between silent and symptomatic episodes. In some patients, silent and symptomatic episodes of similar duration and intensity were observed. Arrhythmias during ischemic episodes such as premature ventricular contractions, ventricular tachycardia, high grade atrioventricular block, and sinus arrest were observed in 32 of 56 patients, 57% of cases and 9% of the total episodes. Arrhythmias were more common during symptomatic episodes (29%) than during silent ones (9%, p less than 0.01), but serious arrhythmias such as ventricular tachycardia, high grade atrioventricular block and sinus arrest occurred even during silent episodes. In both silent and symptomatic episodes, the duration and intensity of ST elevation were significantly lower in ischemic episodes with arrhythmias than in those without arrhythmias. These results suggest that 1) the majority of ischemic events are silent in patients with variant angina; 2) the severity of ischemia seems to be an important factor as the cause of anginal pain, but additional factors may be involved; 3) arrhythmias were more common during sympatomatic than silent episodes.     

Treatment of patients with exercise-induced angina pectoris with korinfar and isoptin

Forty-eight patients with stable angina of effort of II and III functional classes were investigated to compare the efficacy of the calcium antagonists corinfar and isoptin, using placebo and a simple cross-over design of the study. The two drugs were found to have a high antianginal effect expressed in a statistically significant reduction of the incidence of anginal attacks and an increased tolerance to load as compared to placebo. The degree of the antianginal action of corinfar in a daily dose of 40 mg and isoptin in a dose of 240 mg was approximately the same. In some patients the antianginal effect of corinfar and isoptin was associated with an elevation in the pulse-pressure index at the peak of the load, which may be accounted for by the direct coronarodilatory action of these drugs.     

Limitations of ergonovine testing in patients with variant angina

Fourteen patients with variant angina underwent ergonovine testing during diagnostic coronary angiography. The clinical electrocardiographic or angiographic manifestations of coronary artery spasm could not be reproduced in six of these patients. Five patients had chest pain and transient ST-segment elevation within 4 days of the ergonovine study, including three who developed coronary spasm in the catheterization laboratory. It appears that the sensitivity of ergonovine testing in the diagnosis of coronary spasm is lower than previously emphasized.     

HLA antigens in patients with variant angina in Japan

There have been few reports on examining the susceptibility of variant angina. Accordingly, the major histocompatibility complexes (HLA-A, -B, -C, -DR) of unrelated Japanese patients with variant angina were examined. There were no significant differences in the frequency of HLA-A,-B, -C, and -DR antigens between patients and controls (n = 100). Although endothelial dysfunction with pathological abnormalities is suggested to be one of the etiological factors in vasospasm, immunogenetic abnormalities linked to HLA system might not play a role in the pathogenesis of variant angina.     

High remnant lipoprotein levels in patients with variant angina

BACKGROUND: Dyslipidemia with increased oxidative stress but without elevation of low-density lipoprotein cholesterol has been recently implicated in the pathogenesis of coronary vasospasm. HYPOTHESIS: Disordered triglyceride-rich lipoprotein metabolism may be linked to the genesis of coronary artery spasm. METHODS: Both serum remnant lipoprotein (RLP) and alpha-tocopherol levels were determined in 18 patients with the active stage of variant angina (VA), in 16 patients with the inactive stage of variant angina (IVA), and in 19 control subjects (CONTROL). RESULTS: The RLP levels were significantly (p < 0.05) higher in VA (6.4 +/- 2.7 mg/dl) than in IVA (4.4 +/- 1.5 mg/dl). In contrast, alpha-tocopherol levels were significantly lower in VA than that in CONTROL. Serum trigyceride levels were not significantly different among the study groups, although serum high-density lipoprotein cholesterol levels were significantly lower in VA than in CONTROL. Smoking was significantly (p < 0.05) more prevalent in VA (72%) than in IVA (25%) and CONTROL (37%). Serum RLP levels correlated positively with triglyceride levels (R = 0.73) and correlated inversely with alpha-tocopherol levels (R = -0.31) significantly in all study subjects. CONCLUSIONS: Patients with active stage of variant angina had higher RLP levels than inactive patients with variant angina and lower alpha-tocopherol levels than control subjects. Disordered triglyceride-rich lipoprotein metabolism with increased oxidative stress appears to be linked to the activity of coronary vasospasm, suggesting a possible role in its pathogenesis.     

Effects of phentolamine and atropine on angina pectoris induced by handgrip test in patients with variant angina

In 19 patients with variant angina, handgrip test as an isometric exercise was performed in 3 conditions on different successive days in the early morning: in the control, after administration of phentolamine (0.3 mg/kg) and after administration of atropine sulfate (0.04 mg/kg). Angina associated with ST-segment elevation on the electrocardiogram was induced in 5 patients (26%) in the control condition, in 14 (74%) after phentolamine and in 5 of 16 (31%) after atropine. All anginal events but 1 occurred after the cessation of the exercise and were not associated with the significant increase of rate-pressure products. These attacks were considered to be due to coronary spasm. The frequency of the induction of angina was significantly higher after phentolamine than in the other 2 conditions (p less than 0.01). It is concluded that the attack can be induced by the handgrip exercise in a sizable number of patients with variant angina, and that the administration of phentolamine increases the incidence of angina induced by handgrip exercise. The mechanism or mechanisms by which coronary spasm is induced by handgrip exercise remains to be elucidated.     

Provocation of coronary spasm by dopamine in patients with active variant angina pectoris

The effects of dopamine on arteries are different depending on the dose, route of administration, and receptor population. Its administration can cause vasodilation by stimulation of dopaminergic receptors, vasoconstriction by stimulation of alpha-adrenergic and serotonergic receptors, and even spasm of cerebral arteries when given intracisternally in dogs. The ability of dopamine to provoke coronary spasm was assessed in 18 patients with active vasospastic angina in whom this amine was infused at rates of 5, 10, and 15 micrograms/kg/min for periods of 5 min each. The 12-lead electrocardiogram and blood pressure (cuff) were monitored throughout the whole test. In nine patients dopamine caused angina and ischemic electrocardiographic changes suggestive of coronary spasm: ST segment elevation in six patients and ST segment depression in the absence of important coronary stenoses in the remaining three. Infusion of dopamine was repeated during coronary angiography in three patients with positive test results: this provoked occlusive coronary spasm with ST segment elevation in two patients and nonocclusive spasm with ST segment depression in the remainder. In conclusion, infusion of dopamine provokes coronary spasm in a sizeable proportion of patients with active vasospastic angina. Its administration may be detrimental in patients susceptible to coronary spasm, such as those with acute myocardial infarction.     

Comparative results of coronary intervention in patients with variant angina versus those with non-variant angina

Coronary angioplasty is reported to be feasible and safe in patients with coronary spasm and fixed stenosis. However, the long-term results are not positive. We compared the results of coronary angioplasty in 20 patients with variant angina versus 17 patients with non-variant angina among 231 consecutive patients with vasospastic angina. Coronary angioplasty was performed successfully in all 37 patients without any complications. Stenting for coronary dissection or recoil was performed in 8 patients, directional coronary atherectomy was selected for ostial lesion of left anterior descending coronary artery stenosis in 2 patients, and standard balloon angioplasty was performed in 27 patients. There were no clinical differences between the two groups. The restensois rate in patients with variant angina was similar to that in patients with non-variant angina (30% vs 29%, ns). There was no relationship between the provoked spasm and restenosis. During the follow-up period, no major complications were observed in patients with variant angina or those with non-variant angina. In conclusion, full medication with calcium channel antagonists and isosorbide dinitrate, and treatment by coronary angioplasty including the use of new devices, were useful treatments for patients with coronary vasospasm and significant organic stenosis. There was no difference concerning the results of coronary intervention between the patients with variant angina and those with non-variant angina.     

TTS-nitroglycerin and slow-release metoprolol: efficacy in patients with stable exercise-induced angina

The antianginal efficacy of slow-release metoprolol (SRM) alone and associated to a transdermal therapeutic system containing nitroglycerin (TTS-TNG), was investigated in 10 patients with chronic, stable exertional angina and angiographic evidence of obstructive coronary artery disease, by means of a double blind, cross-over trial. Each patient performed a symptom-limited exercise test 4 and 24 hours after single blind placebo on day 1, and double blind SRM (200 mg) alone or SRM plus TTS-TNG, on days 3 and 5, in a randomized sequence. The protocol of Redwood was employed. Compared to the beta-blocker alone, the combined administration of SRM and TTS-TNG was associated to a significant increase in mean exercise duration 4 hours (528 +/- 180 vs 412 +/- 110 sec.; p less than 0.001) and 24 hours (432 +/- 115 vs 391 +/- 100 sec.; p less than 0.05) after drug administration. A significant increase in mean total work performance 4 hours (4626 +/- 1070 vs 3272 +/- 803 kgm; p less than 0.01) and 24 hours (3445 +/- 1045 vs 2941 +/- 773 kgm; p less than 0.01) after drug administration was observed as well. During placebo all the tests were stopped due to angina associated with ST depression greater than or equal to 1 mm. Conversely, the test was terminated due to fatigue by 8 patients at 4 hours and 5 patients at 24 hours after combined therapy, and respectively by 5 and 1 patient after SRM alone. No side effects were observed after the administration of SRM alone, whereas 5 patients complained of mild headache after SRM and TTS-TNG.(ABSTRACT TRUNCATED AT 250 WORDS)