Koshi Matsuyama

Sensitivity and specificity of intracoronary injection of acetylcholine for the induction of coronary artery spasm.

Intracoronary injection of acetylcholine has been shown to induce coronary spasm in patients with variant angina. To examine its sensitivity and specificity, incremental doses of acetylcholine (20, 50 and 100 micrograms into the left coronary artery and 20 and 50 micrograms into the right coronary artery) were injected into the coronary artery or arteries in 70 patients with variant angina (Group 1) (mean age 57 years) and 93 patients without variant angina or angina at rest (Group 2) (mean age 54 years). Forty patients of the latter group had atypical chest pain, 16 cardiomyopathy, 14 arrhythmia, 11 valvular disease, 7 stable effort angina due to advanced coronary artery disease, 3 congenital heart disease and 2 hypertension. A temporary cardiac pacemaker set at 40 to 50 beats/min was positioned in the right ventricle. Coronary spasm was defined as total occlusion or severe vasoconstriction associated with chest pain or ischemic ST changes on the electrocardiogram or both. In Group 1, acetylcholine induced spasm in 63 (90%) of the 70 patients in the artery or arteries predicted to be responsible for spontaneous attacks. In Group 2, acetylcholine induced coronary spasm only in one patient with effort angina and advanced coronary artery disease although lesser degrees of vasoconstriction (less than or equal to 75% of the luminal diameter) occurred in most patients after acetylcholine (specificity of acetylcholine thus was 99%). In conclusion, intracoronary injection of acetylcholine is sensitive and reliable for the induction of coronary spasm.

Entrainment of idiopathic ventricular tachycardia of left ventricular origin with evidence for reentry with an area of slow conduction and effect of verapamil

Recurrent sustained ventricular tachycardia (VT) with QRS morphology of the right bundle branch block and left axis deviation was studied in 4 patients without any underlying heart diseases. The mean VT rate was 155 beats/min and the endocardial catheter mapping during VT showed the earliest activation site at the left ventricular lateral wall near the apex. In all patients, rapid pacing from the right ventricular outflow tract during VT resulted in constant fusion beats except for the last entrained beat (thus VT was entrained), while pacing from the right ventricular apex and from the earliest activation site failed to demonstrate entrainment. During entrainment from the right ventricular outflow tract (mean pacing rate 168 beats/min), conduction intervals from the pacing site to the earliest activation site (St-A interval) and to the right ventricular apex (St-B interval) were measured in 3 patients. The St-A intervals were 400, 410 and 440 ms and the St-B intervals were 80, 70 and 90 ms, respectively. A small dose of verapamil (1.0 mg) was administered during VT, which resulted in a decrease of VT rate by a mean of 23 beats/min. During entrainment from the right ventricular outflow tract the St-A interval was prolonged in all 3 patients while the St-B interval remained the same. In conclusion, the mechanism of this VT was best explained by reentry with an area of slow conduction. Verapamil slowed the rate of VT by prolonging conduction within the area of slow conduction. Tachycardia entrainment makes possible a selective examination of antiarrhythmic drug effect on the area of slow conduction within the reentry circuit of VT.

Effects of intracoronary injection of acetylcholine on coronary arterial diameter

The effects of intracoronary injection of acetylcholine on coronary arterial diameter was examined by coronary arteriography in 30 adult patients (13 men, 17 women), aged 23 to 67 years (mean 51), with normal or almost normal coronary arteriographic findings. Patients with angina pectoris, myocardial infarction and other severe cardiac diseases were excluded. Two minutes after injection of 30 to 100 micrograms of acetylcholine into the left coronary artery, significant diffuse narrowing (more than 25% reduction in diameter) of the left main trunk, the proximal, mid- and distal left anterior descending artery, and the proximal, mid- and distal left circumflex artery occurred in 1 (4%), 5 (20%), 3 (12%), 9 (36%), 6 (24%), 8 (32%) and 3 (12%) of 25 patients, respectively. After injection of 30 to 50 micrograms of acetylcholine into the right coronary artery, significant diffuse narrowing of the proximal, mid- and distal right coronary artery occurred in 5 (25%), 7 (35%) and 10 (50%) of 20 patients, respectively. However, significant diffuse dilatation (more than 25% increment in diameter) appeared in the left main trunk, left anterior descending, left circumflex and right coronary arteries in a few patients. These results indicate that acetylcholine induces coronary vasoconstriction in a significant number and coronary vasodilatation in a small number of adult humans, and that response of the coronary artery to acetylcholine varies along the course of the coronary artery.

Hyperventilation-induced simultaneous multivessel coronary spasm in patients with variant angina: an echocardiographic and arteriographic study

Left ventricular wall motion abnormalities during an attack of coronary spasm induced by hyperventilation were examined with use of two-dimensional echocardiography in 27 patients with variant angina. Transient abnormal wall motion (asynergy) confined to one coronary artery region was found in 18 of the 27 patients and transient abnormal motion extending over more than one coronary artery region in the remaining 9 patients. Spasm of more than one major coronary artery was demonstrated separately by coronary arteriography during an attack induced by injection of acetylcholine or ergonovine in seven of the nine patients who manifested asynergy in more than one coronary artery region. In one patient, spasm was demonstrated in one major coronary artery, and the other coronary arteries were severely stenosed or occluded organically. In the remaining patient, acetylcholine was not injected into both arteries; however, the attack was sometimes associated with ST segment elevation in the anterior leads and at other times in the inferior leads. Therefore, simultaneous multivessel coronary spasm seems to have occurred in eight of the nine patients who exhibited asynergy in more than one coronary artery region. The 8 patients with simultaneous multivessel coronary spasm had a higher degree and longer duration of ST segment elevation and a higher incidence of arrhythmias during the attack induced by hyperventilation than did the 19 patients with single vessel coronary spasm, and all of them had no significant organic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnesium Deficiency Detected by Intravenous Loading Test in Variant Angina Pectoris

To study whether magnesium (Mg) deficiency is present in patients with variant angina, 24-hour Mg retention of low dose Mg (0.2 mEq/kg lean body weight) administered intravenously over 4 hours in 20 patients with variant angina was examined. No patient had received calcium antagonists before or during the study. All had attacks of chest pain associated with ST elevation on electrocardiograms. Twenty-one subjects without ischemic heart disease were studied as control subjects. Ten patients with variant angina were restudied 10 to 529 days (mean 235 +/- 30) after the treatment with calcium antagonists (diltiazem 120 to 240 or nifedipine 40 to 80 mg/day), which resulted in complete suppression of anginal attacks. The mean serum Mg concentrations in the patients with variant angina and the control subjects were 2.1 +/- 0.05 and 2.1 +/- 0.03 mg/dl, respectively (difference not significant). However, 24-hour Mg retention in the patients with variant angina was 60 +/- 5%, while that in the control subjects was 36 +/- 3% (p less than 0.001), suggesting that Mg deficiency is present in at least some patients with variant angina. The mean serum Mg concentrations before and after calcium antagonist treatment in 10 patients with variant angina were 2.1 +/- 0.09 and 2.1 +/- 0.07 mg/dl, respectively (difference not significant). However, 24-hour Mg retention decreased significantly (p less than 0.01) from 60 +/- 6 to 34 +/- 7% after the treatment. There is Mg deficiency in many patients with variant angina and it is corrected after treatment with calcium antagonists.

Effect of H1receptor stimulation on coronary artery diameter in patients with variant angina: Comparison with effect of acetylcholine

It has been suggested that histamine is involved in the pathogenesis of coronary spasm but its exact role remains unclear. H1 receptor stimulation of the coronary artery was performed with a selective intracoronary infusion of histamine (2 micrograms/min) in 21 patients with variant angina after blockade of the H2 receptor with cimetidine (25 mg/kg) and its effect on the coronary artery diameter was examined. Intracoronary injection of acetylcholine was also performed in 19 of the 21 patients. Ergonovine (0.2 mg) was intravenously administered in one patient. The coronary artery diameter was measured with cinevideodensitometric analysis. A mean plasma histamine concentration in the coronary sinus increased from 4 x 10(-9) to 7 x 10(-8) M 5 min after histamine infusion into the left coronary artery (n = 18). Coronary spasm was induced in 6 patients (29%) with histamine, in 18 (95%) with acetylcholine and in 1 with ergonovine. The effect of histamine on the luminal diameter was analyzed at the site of spasm in the 26 coronary arteries in which spasm was induced by acetylcholine or ergonovine. Of the 20 coronary arteries with a normal arteriogram or a fixed stenosis less than or equal to 50% of luminal diameter, histamine decreased the diameter in 4, increased it in 14 (70%) and caused no change in 2; of the 6 coronary arteries with a fixed stenosis greater than or equal to 75%, histamine decreased the diameter in 5 and increased it in 1. In the coronary arteries in which spasm was not induced by either acetylcholine or ergonovine, histamine increased the diameter, especially in those without advanced atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina

The effects of intravenous magnesium on exercise-induced angina were examined in 15 patients with variant angina and in 13 patients with stable effort angina and were compared with those of placebo. Symptom-limited bicycle exercise and thallium-201 myocardial scintigraphy were performed after intravenous administration of 0.27 mmol/kg body weight of magnesium sulfate and after placebo on different days. In all patients, serum magnesium levels after administration of magnesium sulfate were about twofold higher than levels after placebo. Exercise-induced angina associated with transient ST segment elevation occurred in 11 patients with variant angina receiving placebo and in only 2 of these patients receiving magnesium (p less than 0.005). On the other hand, exercise-induced angina was not suppressed by magnesium in any patient with stable effort angina. In these patients there was no significant difference in exercise duration after administration of placebo versus after administration of magnesium. The size of the perfusion defect as measured by thallium-201 scintigraphy was significantly less in patients with variant angina receiving magnesium than that in those receiving placebo (p less than 0.001), whereas it was not significantly different in patients with stable effort angina receiving placebo versus magnesium. In conclusion, exercise-induced angina is suppressed by intravenous magnesium in patients with variant angina but not in patients with stable effort angina. This beneficial effect of magnesium in patients with variant angina is most likely due to improvement of regional myocardial blood flow by suppression of coronary artery spasm.

Effects of intracoronary injection of acetylcholine on coronary arterial hemodynamics and diameter.

To examine the effects of intracoronary injection of acetylcholine on coronary blood flow and on coronary arterial diameter in humans, acetylcholine was injected into the left coronary artery in 32 adult patients (21 men and 11 women with a mean age of 54 years, range 37 to 65) with normal or almost normal coronary arteriographic findings. Patients with angina pectoris, myocardial infarction and severe cardiac diseases were excluded. Temporary right ventricular pacing was set at a rate of 60 beats/min to prevent transient bradyarrhythmias during intracoronary injection of acetylcholine. Measurements of coronary sinus blood flow and coronary vascular resistance and quantification of coronary arterial diameters using a computer-assisted technique were performed before and after each injection of 20, 50 and 100 micrograms of acetylcholine. Significant increase in coronary sinus blood flow and significant decrease in coronary vascular resistance occurred after intracoronary injection of acetylcholine. In contrast, mean diameter of normal epicardial coronary artery tended to decrease and that of irregular epicardial coronary artery decreased significantly after intracoronary injection of acetylcholine. Intracoronary injection of acetylcholine increases coronary blood flow, suggesting vasodilation in the coronary arteriolar bed, while it induces vasoconstriction in most of epicardial coronary arteries in adult humans.

Simultaneous multivessel coronary artery spasm demonstrated by quantitative analysis of thallium-201 single photon emission computed tomography

Thallium-201 myocardial scintigraphy with quantitative analysis of emission computed tomography was performed during episodes of angina in 19 patients with variant angina and nearly normal coronary arteriographic findings. Eleven patients (group I) were shown by arteriography to have spasm in 2 or more large coronary arteries. Eight patients (group II) had spasm in only 1 coronary artery. In 7 patients in group I, significant diffuse perfusion defects simultaneously appeared in multiple coronary artery regions on the scintigram (group IA). The extent and severity of the perfusion defect as measured by thallium-201 tomography were significantly greater in group IA than in group II (p less than 0.001 and p less than 0.01, respectively). The duration of transient ST-segment elevation during the attack in group IA was significantly longer than in group II (p less than 0.001). The incidence of ventricular arrhythmias, including ventricular tachycardia, or complete atrioventricular block during the anginal attack was significantly higher (p less than 0.05) in group IA than in group II. In all study patients, neither attack nor scintigraphic perfusion defect appeared on the repeat test after oral administration of nifedipine. In conclusion, multivessel coronary artery spasm simultaneously appears and causes the attack in many patients with variant angina and nearly normal coronary arteriographic findings, and myocardial ischemia due to simultaneous multivessel coronary spasm is likely to be more extensive and severe, persist longer and have a higher frequency of potentially dangerous arrhythmias than that due to spasm of only 1 coronary artery.

Increased plasma fibrinopeptide a levels during attacks induced by hyperventilation in patients with coronary vasospastic angina

Plasma fibrinopeptide A levels, beta-thromboglobulin levels and platelet factor 4 levels were estimated by enzyme-linked immunosorbent assay before and after hyperventilation in 12 patients with coronary vasospastic angina and in 12 control subjects matched for age and gender. In all 12 study patients, anginal attacks accompanied by electrocardiographic (ECG) changes (ST elevation in 11 patients and ST depression in 1 patient) were induced by hyperventilation. Coronary angiography was performed on 11 of the 12 patients, and coronary artery spasm with the same ECG changes was induced by intracoronary injection of acetylcholine in all 11. The plasma fibrinopeptide A levels increased significantly from 2.0 +/- 0.4 to 10.0 +/- 2.4 ng/ml during the attack (p less than 0.001) in the study patients, but remained unchanged before and after hyperventilation in the control subjects. The plasma levels of beta-thromboglobulin and platelet factor 4 remained unchanged after hyperventilation in both groups. Our data indicate that coronary artery spasm may induce thrombin generation and trigger thrombus formation in the coronary artery.