Clinical Perspectives Coronary stenosis vasoconstriction: impact on myocardial ischaemia

Coronary vasomotor tone has been recognized to play a crucial role in determinating the ischaemic threshold and the occurrence of spontaneous as well as exercise-induced myocardial ischaemia. The traditional concept of the 'rigid tube' has been changed during the past 15 years and the coronary arteries are considered today to represent a 'dynamic tube'. Changes in coronary artery dimensions are caused through the contraction and relaxation of the smooth musculature within the vessel wall. Vasoactive substances released from the endothelium play a crucial role in the regulation of vessel size and coronary vasomotor tone. The endothelium is the largest and most active paracrine organ in the body, producing potent vasoactive, procoagulant, fibrinolytic, and anticoagulant substances. Thus, a diseased coronary endothelium may have a dramatic effect on the function of the vessels and may cause or contribute to the occurrence of myocardial ischaemia under high demand situations, such as physical exercise or mental stress. An important variable in this regulation is coronary blood flow. whereas a-adrenergic blockade has been shown to reduce attacks of variant angina and to abolish coronary vasoconstriction. However, an increase in /?-adrenergic tone has been associated with coronary artery vasodilation'. Coronary vasomotion is an important determinant of myocardial perfusion, not only in normals but also in patients with angina pectoris''. Disturbances in vasomotion are closely linked to the development of atherosclerosis and play an integral part in the pathophysiology of myocardial ischaemia'. In patients with angina pectoris, there is a circadian variation in ischaemic events, being most frequent in the morning hours'. This is due to the enhanced release of epinephrine and norepinephrine', which results in an increase in heart rate and blood pressure as well as enhanced platelet aggregability. Accordingly, vascular resistance has been shown to be increased and ischaemic threshold to be reduced in the morning hours'. This enhanced release of catecholamines leads to coronary vasoconstriction and transient reductions in coronary blood flow with a spontaneous decrease in anginal threshold, a condition referred to as 'mixed angina'.