Louis F. Bishop lecture. Role of coronary artery spasm in symptomatic and silent myocardial ischemia

The revival of the concept of coronary spasm has stimulated research into coronary artery disease. Observations in patients with variant angina have substantially contributed to the appreciation of painless myocardial ischemia. However, the presence or absence of pain during ischemic episodes is not related to the cause of ischemia, because painless ischemia can be observed in variant angina (caused by spasm), in effort-induced angina (caused by increased myocardial demand) and in myocardial infarction (caused by thrombosis). Continuous monitoring initially of patients with variant angina and subsequently of patients with unstable and stable angina proved that often painful and painless ischemic episodes are caused by a transient impairment of regional coronary blood flow rather than by an excessive increase of myocardial demand. The transient impairment of coronary flow appears to be caused by dynamic stenosis of epicardial coronary arteries. This most often occurs at the site of atherosclerotic plaques encroaching on the lumen to a variable extent. Dynamic stenosis can be caused by 1) "physiologic" increase of coronary tone, as in stable angina, 2) spasm, as in variant angina, and 3) thrombosis, usually in combination with "physiologic" changes in tone or with spasm, or both, as in unstable angina. The mechanisms of spasm, as typically observed in variant angina, are different from those of "physiologic" increase of tone; they appear to be related to a local alteration that makes a segment of coronary artery hyperreactive to a variety of constrictor stimuli causing only minor degrees of constriction in other coronary arteries. The nature of this abnormality, which may remain stable for months and years, is yet unknown.     

Mechanisms of myocardial ischemia.

Traditionally, myocardial ischemia has been viewed as an imbalance in the supply and demand of myocardial oxygen. Stable angina is usually considered to involve a fixed lesion, whereas unstable angina involves a fixed lesion as well as such components as platelet aggregation, thrombotic processes, and vasospasm. Variant angina involves primarily vasospasm. A newer concept holds that most angina results from mixed mechanisms in which both fixed lesions and vasomotor alterations play a role. These mechanisms are responsible for mixed ischemic events, characterized by episodes at varying levels of exertion, with or without anginal pain. This concept would seem to be supported by the occurrence of silent ischemia in the setting of stable, unstable, or variant angina, despite differing pathophysiologic conditions. Ischemic events have important prognostic significance; unfortunately, many are unrecognized by patients. The question whether the treatment of ischemic events will improve prognosis remains a matter of debate.     

Silent myocardial ischemia after acute myocardial infarction.

Silent ischemia after myocardial infarction has definite prognostic significance but should be interpreted within the context of other prognostic indicators. The rationale for therapeutic intervention is based on the prognostic implications of silent ischemia and the potentially deleterious effect of repeated episodes of ischemia on the integrity of the left ventricle. We measured parameters of ischemia in 20 patients who showed asymptomatic ischemic ST-T changes on exercise testing in the early phase after myocardial infarction. After diltiazem administration, a reduction of exercise-induced ST-T depression from 2.3 +/- 0.8 to 0.7 +/- 0.6 mm (p less than 0.01) occurred, and regional wall-motion score at exercise, determined by radionuclide angiography, improved significantly (p less than 0.02). These and other observations warrant further studies in which the duration, severity and frequency of the ischemic episodes should be quantified and correlated with prognosis after myocardial infarction.     

Experimental myocardial ischemia. III. Protective effect of glucose on myocardial function

Glucose has been long known as an important substrate for muscle cells and a number of laboratories have demonstrated that carbohydrate metabolism can contribute significantly to energy production both in aerobic and anerobic heart muscle. It has been suggested that these findings may have additional application in localized myocardial ischemic and infarction. Accordingly, experiments were performed to determine the effect of glucose on the mechanical and electrical activity of the heart.Left ventricular pressure (LVP), left ventricular $\text{d}\text{p}\text{d}\text{t}$ ($\text{LVd}\text{p}\text{d}\text{t}$, left ventricular end diastolic pressure (LVEDP), and the incidence of ventricular premature beats (VPB) and ventricular fibrillation (VF) were determined before and after ligation of the anterior descending coronary artery in three different canine heart experimental models.Thirty minutes after ligation of the left anterior descending coronary artery, the mean left ventricular pressure and mean left ventricular $\text{d}\text{p}\text{d}\text{t}$ in the control group had decreased by 85 ± 6% and 74 ± 5% respectively. Under similar conditions glucose treatment produces an increase in left ventricular pressure and left ventricular $\text{d}\text{p}\text{d}\text{t}$ of 111 ± 5% and 123 ± 8% respectively. The simultaneously measured mean left ventricular end diastolic pressure was 7.2 ± 0.9 ml for the control group and 3.7 ± 1 for the glucose treated group. Eighty-three percent of the control dogs developed ventricular ectopic activity. Fifty-eight percent of the control hearts developed ventricular fibrillation. In contrast, only 10% of the glucose treated hearts demonstrated ventricular ectopic activity and only 10% developed ventricular fibrillation.Glucose, as a bolus, consistently improved myocardial contractility and prevented ventricular fibrillation even after serum osmolality and serum glucose levels had returned to normal. These results demonstrate that glucose has a protective effect on the electrical and mechanical function of the canine heart during acute segmental myocardial ischemia. These findings may have application in the treatment of acute myocardial infarction in man.     

Wire-induced myocardial ischemia: a novel approach to create myocardial ischemia in rats.

BACKGROUND: Animal models are indispensable in order to investigate the mechanism of various diseases and to explore the counter measures for those disease states. Although there are several animal models of ischemic heart diseases, surgical interventions required to create myocardial ischemia sometimes give rise to a problem in the yield of model. This study describes a new technique for inducing myocardial ischemia in rats. METHODS AND RESULTS: A 0.014-inch guidewire was introduced via the carotid artery and selectively advanced into the coronary arteries under fluoroscopy. Transmural myocardial ischemia was confirmed by ST-segment elevation and by the appearance of left ventricular wall motion abnormalities on the echocardiogram. Reversibility of the wire-induced myocardial ischemia was demonstrated by complete resolution of both ST-segment elevation and wall motion abnormalities after removing the wire. CONCLUSION: Wire-induced myocardial ischemia was reproducible and is less invasive than conventional ischemic models in rats. This method is a powerful and useful tool for the investigation of ischemic heart disease in small animals.     

Observations on blood viscosity changes after acute myocardial infarction.

Serial blood rheologic measurements were made in 25 patients with acute myocardial infarction; measurements included blood and plasma viscosities, hematological data and plasma protein concentrations. The blood viscosity was elevated on admission and for more than 21 days after acute myocardial infarction. However, the cause of the elevated viscosity was changed as a function of time after acute myocardial infarction. During the first three days after admission, the high blood viscosity was mainly attributable to high hematocrit values. Thereafter, the hematocrit fell, but blood viscosity remained high. High blood viscosity after the first three days of acute myocardial infarction can be correlated with increases in plasma viscosity and red cell aggregation, which in turn are explained by elevations of alpha 2 globulin and fibrinogen concentrations. Patients with higher blood viscosity on admission had a significantly higher incidence of complications, i.e., shock, thromboembolism and left ventricular failure.     

Silent myocardial ischemia. A clinical perspective.

Silent myocardial ischemia has been shown to occur far more frequently than anginal episodes in patients with coronary artery disease. Both an increase in myocardial oxygen demand and abnormalities of coronary vasomotor tone appear to play a significant role in the genesis of silent ischemia. Recent data show that in excess of 40% of patients with stable angina have frequent episodes of silent ischemia. The presence of silent ischemia predicts an increased risk of coronary events and cardiac death. Based on these data, it has been proposed that anti-ischemic therapy should be directed toward control of total ischemic burden. Although several recent studies have demonstrated efficacy of various antianginal drugs in reducing the number and duration of silent ischemic episodes, none has demonstrated beneficial effect on the associated adverse prognosis.     

Sinoventricular conduction during acute myocardial ischemia.

A case with sinoventricular conduction and sinus bradycardia during unstable angina pectoris is presented. Although His bundle electrogram showed atrial and His bundle deflection no P waves could be observed in any surface leads even when effective high right atrial pacing was performed. It may be assumed that the electric or sinus impulses are conducted over the specialized atrial tracts while atrial muscle is in a refractory state due to myocardial ischemia.     

Silent myocardial ischemia. Contribution of coronarography

Coronary angiography enables to determine the true frequency of silent myocardial ischemia (SMI) and specify its prognostic value. Three types of populations are studied. First, patients who are completely asymptomatic and without any past history. The prevalence of coronary disease in this group depends on the age and varies between 2 and 12 p. cent. Then patients with a known coronary insufficiency (past history of myocardial necrosis, for instance). After infarction, in 100 patients evaluated, 50 are asymptomatic and, however, half of them present a SMI. Among those, coronary angiography discloses pluritruncular lesions in half of the cases. And finally, patients with diffuse myocardial disease. 14 p. cent of primary myocardiopathies are of ischemic origin, with diffuse coronary lesions and a severe prognosis.     

Asymptomatic myocardial ischemia

The concept, physiopathology, epidemiology, diagnostic procedures, prognosis and treatment of asymptomatic myocardial ischemia are reviewed. Hypotheses given to explain the absence of pain in the presence of myocardial ischemia are analyzed; Cohn's classification of asymptomatic myocardial ischemia is described and complemented with other clinical entities of painless myocardial ischemia. Prevalence of asymptomatic myocardial ischemia in different groups of patients is also discussed as well as the most important characteristics of diagnostic procedures. Finally the prognosis of asymptomatic myocardial ischemia is analyzed and the present therapeutic possibilities are discussed.