Variant Form Of Angina Pectoris Research Articles

Coronary Artery Spasm as a Cause of Angina

Coronary vasoconstriction has moved in and out of fashion for more than a century. The initial descriptions of angina considered vasomotor instability as a key mechanism,1 but pathologic studies2 and the invention of coronary angiography in the middle of the last century focused attention on structural stenoses and occlusions attributed to atheromatous plaques. When Prinzmetal et al3 described a variant form of angina, which was later confirmed as a coronary spasm,4 vasomotor instability returned to the limelight. Variant angina is characterized by symptoms at rest (not exertion) with ST elevation on ECG (not depression). It usually occurs in the early hours of the morning during depressed vagal tone and is associated with occlusion or near occlusion (>90% stenosis) of a focal proximal coronary segment on angiography.

Mechanisms of Coronary Artery Spasm

The term coronary artery spasm (CAS) refers to a sudden, intense vasoconstriction of an epicardial coronary artery that causes vessel occlusion or near occlusion. Although CAS may be involved in other coronary syndromes, it represents the usual cause of variant angina. The variant form of angina was first described in 1959 by Prinzmetal et al,1 who used this term to indicate that angina attacks, unlike the most common form of effort angina, occurred at rest and were associated with ST-segment elevation, rather than ST-segment depression, on the ECG (Figure 1). Because myocardial ischemia occurred in the absence of any change in myocardial oxygen demand, the authors hypothesized that it was caused by an increased tonus of vessels at the level of coronary stenoses.1 Figure 1. (Top) ST-segment elevation in anterior leads, with reciprocal mild ST-segment depression in inferior leads and V6, during an angina attack in a patient with variant angina. (Bottom) Normalization of the ECG after spontaneous resolution of chest pain. Some years later, in fact, coronary angiography, performed during spontaneous angina attacks, demonstrated that CAS is the usual cause of variant angina.2–4 Coronary angiography also showed that CAS could occur at the site of a stenosis (either minor or severe) or in angiographically normal coronary arteries,5 usually at a localized segment of an epicardial artery (focal spasm) (Figure 2).6 However, sometimes CAS involves 2 or more segments of the same (multifocal spasm) or of different (multivessel spasm) epicardial coronary arteries, or may also involve diffusely one or multiple coronary branches.7 Figure 2. Occlusive spasm of the left circumflex coronary artery and near occlusive spasm of the left anterior descending coronary artery (arrows) during coronary angiography (left, top), associated with dramatic ST-segment elevation at monitoring ECG leads (left, bottom). Complete resolution of spasm (right, …

Myron Prinzmetal 1908–1987: The man behind the variant angina

Prinzmetal or variant angina refers to decrease in blood flow secondary to spontaneous spasm of the arterial wall usually without significant atherosclerotic plaques. These symptoms happen at rest and often may wake up the patient during the night. This angina is named after Myron Prinzmetal (1908–1987), who worked most of his life in Los Angeles and published 165 medical publications during his brilliant career. His interests ranged from disease of the lung, kidneys, and peripheral vascular disease to cardiac arrhythmias, circulatory shock, hypertension, and coronary syndromes. In 1959, with Dr. Rexford Kennamer and others, he published their first observations on the variant form of angina pectoris, a landmark report that was to ensure him a place in the annals of medicine. This report describes his life.

Nifedipine: A Novel Vasodilator

Nifedipine was synthesized by Bayer Germany in 1966 and considered for clinical use as a coronary vasodilator in patients with angina pectoris. Japanese investigators played a great part in the pre-clinical and clinical development of nifedipine. Professor Hashimoto demonstrated that nifedipine could increase coronary blood flow even in extremely low dosages, and Professor Kimura found that nifedipine is highly efficacious in preventing anginal attacks in patients with angina pectoris, particularly those with variant form of angina. In early trials it was noted that nifedipine decreased blood pressure in patients with angina pectoris and clinical research by Professor Murakami established a role for nifedipine in the treatment of hypertension. As a prototype L-type calcium (Ca2+) channel antagonist, nifedipine has contributed a great deal to our understanding of the pathophysiological roles of Ca2+ channels in cardiovascular disorders.

CORONARY ARTERY SPASM

INTRODUCTIONIt is now well over 100 years since Latham1 postulated coronary artery spasm as a mechanism for angina pectoris. In 1889, Huchard2 suggested that coronary spasm, superimposed on organic lesions, might explain some aspects of ischaemic heart disease. However, in the 1930s and 40s demonstration of coronary atherosclerosis in pathological specimens led to the concept of obstructive atheroma as the basis for anginal syndromes. In the late 1950s Prinzmetal repopularised Huchard's concept of spasm superimposed on an organic lesion as a basis for angina in some clinical settings (Prinzmetal's variant angina).3 He reported that pain only came on with the subject at rest, or during routine daily activity, rather than with effort. This form of angina is associated with ST segment elevation on the electrocardiogram, rather than with the more usually noted ST depression. Three decades after Prinzmetal described this variant form of angina, there are still doubts about its causation and prevalence.

下がくに発症した連関痛により，異型狭心症が発見された症例

A 76-year-old male, patient with lower jaw pain was studied.Though the patient had no history of angina pectoris and no chest pain, ambulatory electrocardiography showed the elevation of ST segments in early morning, which followed lower jaw pain. This transient elevation of ST segments was reduced by coronary vasodilator and at that time, the lower jaw pain was completely relieved.In this way, a careful history and long-recording electrocardiography established a diagnosis of the variant form of angina pectoris and it reffered pain in the lower jaw.

The role of alpha-adrenergic receptors in the pathogenesis of coronary spasm.

The role of alpha-adrenergic receptors in the pathogenesis of coronary spasm.

Calcium antagonists. Clinical use in the treatment of angina.

Angina pectoris results from an imbalance between the oxygen supply and the oxygen needs of the myocardium. While the classic form of angina is usually caused by demands exceeding supply, a primary and transient decrease in coronary blood flow is more and more often recognised as an aetiological factor of myocardial ischaemia. Calcium antagonists, although new in cardiovascular therapeutics, are already recognised as the treatment of choice for some forms of angina and as useful therapeutic adjuncts in others. Few contraindications to their use exist. They are potent vasodilators and they can prevent the occurrence of coronary artery spasm responsible for the Prinzmetal's variant form of angina. They can also reduce coronary artery tone, which if high, can compromise flow through a narrowed coronary artery. Nifedipine, diltiazem and verapamil can also influence the various determinants of myocardial oxygen consumption to reduce myocardial oxygen needs. Their effects on heart rate, blood pressure and on the inotropic state of the left ventricle is, in vivo, the balance between their direct effects on the vascular wall and myocardial muscular cells and their indirect effects represented by the reflex physiological responses. Significant variations in these effects exist between the 3 calcium antagonists such that treatment can be individualised to a particular patient's needs. Precautions with their use as well as most of their side effects can be understood from a knowledge of their direct and indirect properties. Other pharmacological effects of these drugs include a regional redistribution of coronary blood flow, cardioprotection, delay in cell death and possibly in the progression of atherosclerosis. The clinical significance of these properties remains to be investigated.

Platelet aggregation studies in patients with angina pectoris--relationships to types of angina and coronary pathoanatomy.

Platelet aggregation was studied in patients with angina pectoris in whom coronary sclerosis was found by arteriography. The subjects consisted of 20 patients with stable angina pectoris, 12 with unstable angina pectoris and 4 with variant form of angina pectoris. Fifteen healthy subjects served as controls. ADP- and collagen-induced platelet aggregations were estimated during resting conditions before and immediately after an exercise test. In patients with unstable angina pectoris, ADP-induced as well as collagen-induced platelet aggregations during resting conditions were significantly less than those in normal subjects. After exercise, however, they significantly increased. In stable angina pectoris, they did not differ from those in the control group and their responses to exercise were also not significant. In general, platelet aggregation during resting conditions was accelerated in relation to an increase in the number of coronary arteries involved. The results demonstrate that examination of platelet aggregation during resting conditions and following exercise aids in a more accurate evaluation of the types and the stages of patients with angina pectoris.

Exercise test in variant form of angina pectoris. Comparison of the results with spontaneous attacks.

Exercise tests were performed in 14 patients with untreated variant angina with frequent spontaneous attacks and in 15 patients after treatment abolished the attacks. (1) Anginal attacks associated with ST elevation were induced by exercise in 79% of untreated patients. By contrast, ST elevation was not observed in treated patients and ST depression was induced in 53% of the cases. (2) Exercise-induced ST elevation in untreated patients was shown in the same leads as the spontaneous attacks. (3) Exercise-induced ST elevation appeared initially during the recovery phase after exercise in 36% of untreated patients. Exercise-induced ST depression appeared during or immediately after exercise. (4) The reproducibility of exercise-induced ST elevation was low with repeated tests at different stages, but exercise-induced ST depression was consistently observed. (5) The exercise-induced ST depression and lack of ST changes in treated patients were highly suggestive of the presence and absence of organic coronary artery disease, respectively. However, the exercise-induced ST elevation in untreated patients did not differentiate between the presence or absence of organic stenosis of the coronary arteries. The results of exercise tests vary with the stage of variant angina. It is suggested that a coronary arterial spasm is a trigger mechanism for exercise-induced angina in cases of variant angina with frequent spontaneous attacks.

Anomalous origin of right coronary artery from left sinus of Valsalva with variant form of angina pectoris

Anomalous origin of right coronary artery from left sinus of Valsalva with variant form of angina pectoris

Clinical significance of exercise test in variant form of angina pectoris

Clinical significance of exercise test in variant form of angina pectoris

The mechanism of ergometrine-induced coronary arterial spasm: in vitro studies on canine arteries.

The mechanism by which ergometrine provokes coronary vasospasm was investigated in vitro. Changes in tension were monitored isometrically on spiral strips of freshly obtained coronary (ventricular and circumflex branches) and basilar arteries from dogs. Cumulative concentration-response curves were established for noradrenaline, adrenaline, 5-hydroxytryptamine (5-HT), and ergometrine. The catecholamines either contracted or relaxed the coronary vascular smooth muscle by stimulating alpha- or beta-adrenoceptors, respectively, whereas both 5-HT and ergometrine consistently induced contraction of coronary arteries. In order to antagonize ergometrine-induced contraction on circumflex coronary arteries, appromimately 60-fold greater concentrations of phentolamine were required compared to those necessary for antagonism of noradrenaline. The concentration-response curve for noradrenaline was unchanged by ergometrine, indicating that the two compounds combine with different receptors. The use of the antagonists phentolamine, indoramine, pimozide, pizotifen, and methysergide provided evidence that ergometrine and 5-HT induce contraction of coronary arteries by stimulating the same type of 5-HT receptor, which, however, seems to be different from the 5-HT receptor present in basilar arteries. It is suggested that in Prinzmetal's variant form of angina, ergometrine can provoke coronary vasospasm by increasing the tone of the coronary vascular smooth muscle via stimulation of 5-HT receptors, thus reinforcing sympathetic coronary vascular tone.

Variant Form of Angina Pectoris: Its Clinical Features and Treatment

The variant form of angina pectoris (VA) is a rather common disease in Japan, and the author himself is suffering from it. Among 100 successive cases of various types of angina seen in our Department, excluding myocardial infarction and post-infarctional angina, 23 cases were VA. The brief duration, cyclic occurrence and frequent incidence of the attacks at night are considered to be the clinical characteristics. The pathogenesis of VA is ascribed to coronary spasm on the basis of findings made in cinecoronary arteriography. ST elevation was observed more frequently on exercise test in VA than in ordinary exertional angina pectoris, indicating that patients with VA are in a markedly spasmophilic state. Although the prognosis is not generally so serious, 33 out of 50 cases of VA had arrhythmias during attacks, including such serious ones as advanced AV block and ventricular fibrillation. Nifedipine was dramatically effective in suppressing repeatedly occurring ventricular fibrillation. A survey of the effects of calcium antagonists in 243 cases of VA in 11 cardiology institutes throughout Japan revealed that these drugs were effective in more than 90% of the cases. Of particular note is the fact that the attacks were completely eliminated in more than 80% of the cases.

Thromboxane A 2 as a possible inducer of coronary angiospasm in variant form of angina pectoris

Thromboxane A 2 as a possible inducer of coronary angiospasm in variant form of angina pectoris

Inhibition of Constrictor Responses of Dog Coronary Artery by Atropine

A possible effectiveness of atropine on variant form of angina pectoris was investigated using the left circumflex coronary arterial strips of dogs. Acetylcholine 10(-5)--10(-3) Gm/ml dose-dependently constricted the isolated arterial strips during potassium-contracture in 6 cases, and repetitive applications of acetylcholine could produce the similar contractions to the control. In 18 strips atropine 10(-6) Gm/ml significantly depressed the contractions of coronary arteries induced by acetylcholine 10(-5)--10(-3) Gm/ml. In 5 arterial strips atropine 10(-6) Gm/ml significantly inhibited norepinephrine-induced responses of these arteries, and by 10(-5) Gm/ml further suppression of the responses was obtained. The results suggest that atropine may suppress the contractile responses of the coronary artery induce by acetylcholine and nonrepinephrine through a muscarinic-receptor blocking action and simultaneously partly through an adrenergic alpha-receptor blocking action.

Effect of Diltiazem on Coronary Hemodynamics and Its Clinical Significance

A small electromagnetic flowprobe was chronically implanted in circumflex branch of left coronary artery of mongrel dogs. Diltiazem, 100μg/Kg, was injected in a basilic vein of the unanesthetized dogs. The changes in phasic coronary flow as well as hemodynamics including aortic pressure (AP), heart rate (HR), and myocardial oxygen extraction ratio (OER) were in estigated. The increasing rates of total coronary flow (TCF) 5, 10, and 20min after the injection of the drug were 90%, 65%, and 40% respectively, Total coronary vascular resistence (TCVR) was inversly proportional to TCF, resulting in a significant decrease after injection. Five min after the drug administration, OER markedly decreased to the level of -45% of control value. The changes in aortic pressure (AP) and heart rate (HR) were unremarkable.In clinical investigation, coronary atrery narrowings (spasms) observed by cine coronary arteriography in a patient with a variant form of angina pectoris were completely dilated after intravenous injection of Diltiazem.In conclusion, Diltiazem exerted a powerful and long-acting vasodilator action on coronary vasculature. Although AP and HR showed unremarkable changes after the injection of the drug, OER decreased significantly. Results obtained suggest that Diltiazem can reduce myocardial oxyge consumption and OER and that the decrease in OER is attributed to not only the peripheral hemodynamic effect of the drug but also probable consequence of the direct action on the myocardium.

Prinzmetal's Angina

ALMOST 18 years have passed since Prinzmetal and his colleagues 1 originally described a variant form of angina pectoris characterized by cyclic attacks of chest pain occurring at rest and associated with transient ST-segment elevation. Prinzmetal postulated that these attacks were due to spasm of a major coronary artery. Recently, a number of investigators have reported coronary artery spasm occurring during spontaneous episodes of variant angina confirming Prinzmetal's hypothesis. Since spontaneous attacks of variant angina may be infrequent, specific tests for provoking coronary artery spasm in variant angina would be helpful in the diagnosis and evaluation of therapy in patients with this disorder. This case of a patient with classic Prinzmetal's angina illustrates the clinical presentation, current pharmacologic therapy, angiographic changes associated with pain episodes, an old but revived provocative test, and a new therapeutic agent for treatment of this condition. Report of a Case A 40-year-old woman was awakened at

Clinical profiles of variant form of angina pectoris, with special reference to the observations obtained by pocket-size electrocardiograph

Clinical profiles of variant form of angina pectoris, with special reference to the observations obtained by pocket-size electrocardiograph

Current concepts of Prinzmetal's variant form of angina pectoris.

Current concepts of Prinzmetal's variant form of angina pectoris.