Pathophysiology of Ischemia and Pain Syndrome
In stenosing atherosclerosis, the coronary bed undergoes major hemodynamic changes. In the zone distal to the occlusion site (distal to the atherosclerotic plaque), vessels are constantly in a state of maximal dilation. This compensatory dilation occurs due to tissue hypoxia and the accumulation of local vasodilating metabolites, primarily adenosine.
However, this compensation proves insufficient. Due to the mechanical obstruction of stenosis, oxygen delivery to the heart muscle remains limited. During physical or emotional exertion, a critical imbalance arises: myocardial oxygen demand increases sharply, while the capacity to adequately increase blood flow is absent because the vessels are already maximally dilated.
The molecular mechanism of ischemic pain is directly linked to biochemical shifts. Against the background of hypoxia, protons ($H^+$) accumulate in tissues. They locally stimulate vanilloid receptors, the irritation of which is perceived by the central nervous system as characteristic pain impulses.
Clinical and Pathogenetic Forms of Angina
Clinically, coronary circulatory insufficiency manifests as the syndrome of angina pectoris (angina pectoris). These are episodes of squeezing, pressing pain behind the sternum. Depending on the mechanism disrupting the balance between oxygen demand and delivery, three main forms of the disease are distinguished:
- Effort Angina (Stable, Classic). Develops against the background of stenosing atherosclerosis. The attack is provoked by physical or emotional exertion, when the heart's oxygen demand increases, while the affected vessels are mechanically incapable of dilating. The primary pharmacological goal is to use agents that reduce myocardial oxygen demand.
- Vasospastic Angina (Variant, Prinzmetal Angina). A rare form (occurring in no more than 1% of cases) caused by coronary spasm. Attacks occur spontaneously, often at rest or during sleep, without visible triggering factors. The likely cause is a deficiency of the endothelial-derived relaxing factor. The goal of treatment is to eliminate the spasm by using agents that dilate the coronary vessels.
- Unstable Angina. Caused by massive thrombus formation in the coronary arteries, leading to severe impairment of trophics. Attacks appear at rest and are poorly relieved by standard antianginal drugs. It is considered a dangerous pre-infarction condition requiring the administration of agents that prevent thrombus formation.
Classification of Antianginal Agents
Drugs for the treatment of angina are classified according to how they affect two key factors: myocardial oxygen demand and actual oxygen delivery.
- Group I. Agents that simultaneously decrease oxygen demand and increase its delivery. These include organic nitrates, calcium channel blockers, potassium channel openers, and certain other drugs.
- Group II. Agents that decrease myocardial oxygen demand. This category includes $\beta$-blockers and bradicardic agents.
- Agents that increase oxygen delivery. These are drugs that increase coronary blood flow. They can act myotropically (directly affecting the smooth muscle of the vascular wall) or reflexively (causing vasodilation via reflex mechanisms).
Principles of Complex Pharmacotherapy
Pharmacotherapy for angina pursues two global goals: rapid relief of an already developed pain attack and systematic prophylaxis (course treatment in the inter-ictal period to prevent episodes of ischemia).
Therapy is always comprehensive. In addition to specific antianginal drugs, patients are prescribed:
- Antiplatelet agents (to prevent thrombus formation).
- Hypolipidemic agents (to control lipid levels and inhibit atherosclerosis).
- Angioprotectors (to protect the vascular wall).
A special new direction in treatment is cytoprotection. It implies the use of cardioprotectors that provide metabolic protection for cardiomyocytes and increase their resistance to ischemic conditions.