Masao Nagao

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

Thirteen patients with Prinzmetals variant angina performed treadmill exercise tests in the early morning 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 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 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 Prinzmetals variant angina caused by coronary arterial spasm induced by exercise in the early morning but not in the afternoon.

Long-term prognosis for patients with variant angina and influential factors.

Two hundred forty-five patients with variant angina were followed for an average of 80.5 months (range, 36-184 months). Survival rate at 1, 3, 5, and 10 years was 98%, 97%, 97%, and 93%, respectively. Survival rate without myocardial infarction at 1, 3, 5, and 10 years was 86%, 85%, 83%, and 81%, respectively. By univarite analysis, ST segment elevation in both the anterior and inferior electrocardiographic leads was the most important factor influencing survival, followed by use of calcium antagonists, left ventricular function, smoking, and alcohol intake. The variables that significantly correlated with survival without myocardial infarction were use of calcium antagonists, left ventricular function, extent and severity of coronary artery disease, coronary artery bypass surgery, and disease activity. Multivariate analysis using the Cox proportional hazards model showed that intake of calcium antagonists, extent and severity of coronary artery disease, and ST segment elevation in both the anterior and inferior leads were significant independent predictors of survival without myocardial infarction. We conclude that long-term prognosis for patients with variant angina is relatively good and that use of calcium antagonists improves it.

Coronary arterial spasm and Prinzmetal's variant form of angina induced by hyperventilation and Tris-buffer infusion.

SUMMARY Vigorous hyperventilation was induced for five minutes immediately after a five-minute infusion of 100 ml of Tris-buffer (pH 10) in nine patients with Prinzmetals variant angina. In eight of the patients, chest pain with ischemic changes in the electrocardiogram occurred during this procedure or within five minutes after it ended. Coronary arterial spasm appeared after the procedure and disappeared after the administration of nitroglycerin in all four patients in whom coronary cinearteriography was performed. This was evident both before and after the procedure and after sublingual administration of nitroglycerin (0.6 mg). The oral administration of 90 mg of diltiazem, a calcium antagonistic drug, two hours before, completely suppressed the attack induced by the procedure in all of the five patients who received this drug. We conclude that hyperventilation plus Tris-buffer infusion induces coronary arterial spasm and anginal attack in patients with Prinzmetals variant angina and that diltiazem suppresses these reactions.

Exertional angina pectoris caused by coronary arterial spasm: Effects of various drugs

In four patients with exertional angina induced by arm exercise, coronary arteriograms taken before, during and after the attack demonstrated that spasm appeared in the large coronary artery supplying the area of myocardium shown to be ischemic in the electrocardiogram during the attack. The spasm disappeared with subsidence of the attack after administration of nitroglycerin. Anginal attacks induced by treadmill exercise were not suppressed by propranolol, 60 mg orally, in two of the four patients. However, such attacks were suppressed in all patients by oral administration of diltiazem (90 mg, four patients) or nifedipine (20 mg, three patients) or intramuscular injection of phentolamine (0.2 mg/kg body weight, three patients). It is concluded that coronary arterial spasm can be induced by exercise and can cause exertional angina in some patients. Diltiazem and nifedipine, calcium antagonistic drugs, prevent spasm.

Variant angina induced by alcohol ingestion

We gave alcohol to 15 patients with variant angina to induce the attacks at the hospital. Anginal attacks were repeatedly induced in seven of them. Although the time lag between alcohol ingestion and the attacks varied widely among patients, from 1.5 to 12 hours, it was fairly constant in each patient. We carefully examined the histories of 101 patients with variant angina to become familiar with the relationship between alcohol ingestion and the attacks of angina. Seventy-one patients took alcohol in their daily lives. Nineteen of the 71 patients (26.8%) who took alcohol had a definite relationship between alcohol ingestion and the attacks. We conclude that alcohol induces anginal attacks or coronary artery spasm in not a small number of patients with variant angina.

Alkalosis-induced coronary vasoconstriction: Effects of calcium, diltiazem, nitroglycerin, and propranolol

We examined the effects of changes in pH, Ca2+ concentration, diltiazem, nitroglycerin, and propranolol on the vascular tone of the isolated rabbit coronary artery. Stepwise increase in pH of the bath fluid caused pH-dependent increased vascular tone. Increase in Ca2+ concentration of the bath fluid also resulted in increased vascular tone, while removal of Ca2+ abolished the high pH-induced elevated vascular tone. Diltiazem and nitroglycerin suppressed the high pH-induced increased vascular tone. Propranolol in high concentrations exhibited a direct inhibitory effect on the high pH-induced increased vascular tone. We conclude that high pH induces coronary vasoconstriction principally by increasing transmembrane influx of Ca2+ and that diltiazem and nitroglycerin suppress this action.

A new approach for the enzymatic estimation of infarct size: Serum peak creatine kinase and time to peak creatine kinase activity

The relations of several creatine kinase (CK) variables to angiographic left ventricular ejection fraction and abnormally contracting segments in the chronic phase were examined in 2 groups of patients with a first anterior acute myocardial infarction. In group A (n = 22), emergency coronary angiography was performed and nonsurgical early reperfusion was attempted. Such an early revascularization, which was considered partially present in group B (n = 16), which received conventional therapy, shifted the CK time-activity curve to the left and altered its relation to angiographic cardiac function. At similar levels of peak CK, myocardial damage was significantly smaller in patients with successful thrombolysis than in those with unsuccessful reperfusion and conventional therapy (p less than 0.01). In patients whose infarct was considered to be moderate according to peak CK (1,000 to 3,000 U/liter), there was significant correlation between time to peak CK and left ventricular ejection fraction or percent abnormally contracting segments irrespective of their group. The results suggest that one should take into account rapid washout and shorter time to peak CK when estimating enzymatic infarct size in humans. The multivariate analysis of cardiac function with peak CK and time to peak CK resulted in a closer correlation in all patients. Such a correction in the time to peak CK may be a clinically useful approach for better interpretation of infarct size.

Acute Myocardial Infarction Induced by Ergotamine Tartrate: Possible Role of Coronary Arterial Spasm

A 45-year-old woman with almost normal coronary arteries suffered from acute inferior myocardial infarction after taking 2 tablets (2.0 mg) of ergotamine tartrate for headache. She had had attacks of variant angina and spasm of the right coronary artery had been demonstrated during the attack. After the recovery from myocardial infarction the intravenous injection of ergonovine maleate 0.05 mg induced spasm of the right coronary artery again. We conclude that acute myocardial infarction in this patient was probably caused by coronary arterial spasm induced by ergotamine tartrate.

Pathogenesis of angina pectoris in patients with one-vessel disease: Possible role of dynamic coronary obstruction

We examined the pathogenesis of angina pectoris in 101 patients with one-vessel disease except those with 99% to 100% occlusion. The attacks could not be induced or could not be reproducibly induced by maximal treadmill exercise at the same hour of different days within a week period in 54 (53.5%) of the patients. In the 47 patients whose attacks were reproducibly induced by the exercise, propranolol, 80 mg orally, did not suppress the attacks in 41 (87.2%) of the patients. Diltiazem, 90 mg, and nifedipine, 20 mg given orally, suppressed the attacks completely in 39 (83.0%) of the 47 patients and in 36 (81.8%) of the 44 patients, respectively. Coronary arteriography showed that dynamic obstruction of the artery supplying the area of myocardium represented by ST segment deviation appeared during the attacks and disappeared with subsidence of the attacks in all 55 patients in whom coronary arteriography was done during the attack. We conclude that angina pectoris is usually caused not by increased myocardial oxygen demand but by dynamic coronary obstruction or by a combination of both in most patients with one-vessel disease.

Coronary Arteriographic Findings During Early Hours of Acute Myocardial Infarction: Response to Intracoronary Injection of Nitrates:

We performed coronary arteriography and gave intracoronary injection of nitrates within 8 hours after the onset of symptoms of acute myocardial infarction in eighteen patients. Improved distal filling or patency of the total occluded coronary artery after intracoronary injection of nitrates occurred in 4 of 18 patients. In one of four patients the first intracoronary nitrates injection failed to release the initial total occlusion, but after intracoronary Urokinase administration, the second nitrates injection succeeded to dilate the com pletely occluded coronary artery. Coronary arteriography was again per formed in sixteen patients in the chronic stage (4-15 weeks after the onset of acute myocardial infarction) and ergonovine malaete was injected intraven ously in seven patients. Focal spasm was induced by ergonovine injection in three patients in one of whom intracoronary nitrates failed to release the complete obstruction in the acute stage. We conclude that coronary spasm as well as intracoronary thrombosis plays an important role in the production of acute myocardial infarction.