Hiroo Miyagi

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.

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.

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.

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.

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.

Long-lasting abnormalities in cardiac sympathetic nervous system in patients with coronary spastic angina: Quantitative analysis with iodine 123 metaiodobenzylguanidine myocardial scintigraphy

Quantitative analysis of iodine 123 metaiodobenzylguanidine (MIBG) myocardial tomographic imaging showed that the regional uptake reduction and abnormally high washout of MIBG in the myocardial territories of the coronary artery with spasm were observed in 33 (75%) and in 30 (68%) of 44 patients with coronary spastic angina, whereas it was observed in two (7%) and in four (15%) of 27 control subjects, respectively. The patients with higher disease activity of the anginal attack and those with life-threatening ventricular arrhythmias were frequently associated with either the uptake reduction or the abnormally high washout of MIBG (91% in patients with high disease activity, 100% in patients with ventricular arrhythmias). The repeated studies of MIBG myocardial tomographic imaging at 2 and 6 months after suppression of anginal attacks by medical treatments showed that the scintigraphic abnormalities still remained in 85% of the patients at 2 months and 32% at 6 months. Thus the abnormalities in sympathetic nervous system assessed with MIBG scintigraphy has been shown to be highly associated with patients with coronary arteries with spasm, particularly high-risk patients, and lasted for several months despite suppression of anginal attack.

Therapeutic Angiogenesis for a Patient with Arteriosclerosis Obliterans by Autologous Transplantation of Bone Marrow Mononuclear Cells

A 60 year-old man with atherosclerosis obliterans had received a bypass operation twice, but came to notice resting pain in the left calf. As it was not possible to perform further bypass operations (resulys of arteriography), we conducted conservative treatments. We therefore performed therapeutic angiogenesis by autologous transplantation of bone marrow mononuclear cells since the symptoms were not improved at all. Resting pain was improved the next day after the operation and completely disappeared on the third day. The patient was only able to walk 180m in the preoperative state by crutch-assisted, but walked 180m without a stick on the second day and 900m on the fourth day. This treatment did not cause any inconvenience in everyday life and the patient showed no resting pain eight weeks later. In addition, the ankle-brachial index improved to 0.48 from the preoperation level of 0.36 after two months.

913-114 Abnormal Cardiac Sympathetic Nervous System in Patients with Coronary Spastic Angina; Assessment with Iodine-123 Metaiodobenzylguanidine Myocardial Scintigraphy

We have shown that dysregulation of autonomic nervous system plays an important role in the mechanism(s) of coronary artery spasm. To assess regional abnormalities in cardiac sympathetic nervous system in the mechanism(s) of coronary artery spasm, twenty-eight patients with coronary spastic angina and 10 control subjects were examined with MIBG myocardial tomographic imaging (SPECT) which is a non-invasive and useful method evaluating regional cardiac sympathetic nervous activity. The patients included in this study had neither organic coronary stenosis nor myocardial infarction. MIBG-SPECTwas examined at rest and was avoided to perform during anginal attack. Coronary spasm was documented by coronary angiography during the anginal attack induced by intracoronary injection of acetylcholine in all of the patients. MIBG-SPECT was performed at the time period when spontaneous attack frequently occurred. Regional reduction of MIBG uptake was observed in 30 of 42 areas perfused with coronary arteries having spasm (sensitivity 71%). whereas it was observed in 12 of 73 areas perfused with coronary arteries not having spasm in patients with coronary spastic angina and in control subjects (specificity 84%). Sensitivity for detecting coronary arteries with spasm in the LAD was 69% (9/13 arteries) and that in RCA was 81% (13/16 arteries) and that in LCX was 62% (8113 arteries). MIBG-SPECT was again performed in 7 patients at 4 months after complete suppression of the anginal attack by treatment with calcium antagonists and nitrates without b blocker. The re-studies showed that reduction of MIBG uptake was still observed in the same scintigraphic areas having MIBG uptake reduction at the initial studies in all patients tested. The results show that MIBG-SPECT is a feasible and high sensitive method for predicting the coronary arteries with spasm without provocation of coronary spastic anginal attacks, and sympathetic nervous dysfunction continues for several months after complete suppression of myocardial ischemia, suggesting that sympathetic nervous dysfunction may not be the ischemic effect but playa possible role in the cause of coronary artery spasm.

Comparison of efficacy of nisoldipine, metoprolol, and isosorbide dinitrate in patients with stable exertional angina: a randomized, cross-over, placebo-controlled study

We evaluated the acute antianginal effect of oral nisoldipine (10 mg), metoprolol (40 mg), and long-acting isosorbide dinitrate (20 mg) in 15 patients with stable exertional angina. The patients performed symptom-limited treadmill exercise at 2 h after the administration of placebo (Placebo stages 1 and 2) and each of the active drugs. After Placebo stage 1, the patients were randomized for cross-over evaluation of the acute effect of a single oral dose of placebo (Placebo stage 2), nisoldipine, metoprolol, or long-acting isosorbide dinitrate. All 15 patients developed angina during all of exercise tests and their exercise tests were terminated at the onset of angina. The time until development of 0.1 mV ST segment depression was increased by all three drugs compared to placebo, and it was significantly longer with metoprolol than with isosorbide dinitrate. Similarly, the time to ceasing exercise because of angina was also prolonged by all three drugs. The exercise time was longer with nisoldipine and metoprolol compared to isosorbide dinitrate, but there was no significant difference between nisoldipine and metoprolol. In conclusion, metoprolol and nisoldipine more effectively prolonged exercise compared to long-acting isosorbide dinitrate in patients with stable exertional angina.