The Pharmacologic Treatment of Myocardial Infarction
- THIS PAGE: The Pathophysiology of Myocardial Infarction - Causes and Effects
- Page 2: Rationale for Drug Therapy in Myocardial Infarction
- Page 3: Classes of Drugs Used to Treat Myocardial Infarction
The Pathophysiology of Myocardial Infarction
Myocardial infarction ("heart attack") is the irreversible damage of myocardial tissue caused by prolonged ischemia and hypoxia. This most commonly occurs when a coronary artery becomes occluded following the rupture of an atherosclerotic plaque, which then leads to the formation of a blood clot (coronary thrombosis). This event can also trigger coronary vasospasm. If a vessel becomes completely occluded, the myocardium normally supplied by that vessel will become ischemic and hypoxic. Without sufficient oxygen, the tissue dies. The damaged tissue is initially comprised of a necrotic core surrounded by a marginal (or border) zone that can either recover normal function or become irreversibly damaged. The hypoxic tissue within the border zone may become a site for generating arrhythmias. Collateral blood flow is an important determinant of infarct size and whether or not the border zone becomes irreversibly damaged. Infarcted tissue does not contribute to tension generation during systole, and therefore can alter ventricular systolic and diastolic function and disrupt electrical activity within the heart. After several weeks, the infarcted tissue forms a fibrotic scar. Long-term consequences include ventricular remodeling of the remaining myocardium (e.g., development of compensatory hypertrophy or dilation), ventricular failure, arrhythmias and sudden death.
Myocardial infarctions produce clinical symptoms that include intense chest pain that may radiate into the neck, jaw or arms (i.e., referred pain), a sense of substernal heaviness, squeezing or pressure, shortness of breath (dyspnea), fatigue, fainting (syncope), nausea, sweating (diaphoresis), anxiety, sleeplessness, hypertension or hypotension (depending in part on the extent of cardiac damage), tachycardia and arrhythmias. Recent clinical research indicates that the symptoms may be very different between men and women. Chest pain is less common in women. Instead, their most common symptoms are weakness, fatigue and dyspnea.
Effects of Acute Myocardial Infarction
- sytolic/diastolic dysfunction
- decreased cardiac output
(↓ stroke volume)
- pulmonary congestion/edema
- ↑ sytemic vascular resistance
- ↑ blood volume
- ↑ systemic edema
- sympathetic activation
- ↑ circulating catecholamines
- ↑ angiotensin II and ↑ aldosterone
- ↑ natriuretic peptides
- ↑ arginine vasopressin (ADH)
The pathophysiology of acute myocardial infarction is complex. Loss of viable myocardium impairs global cardiac function, which can lead to reduced cardiac output, and if damage is severe, to cardiogenic shock. Systolic and diastolic dysfunction are associated with ischemic myocardium. If left ventricular function is significantly impaired, pulmonary congestion and edema can occur. Ischemia can also precipitate abnormal cardiac rhythms and conduction blocks that can further impair function and become life-threatening in some cases. Reduced cardiac output and arterial pressure can elicit baroreceptor reflexes that lead to activation of neurohumoral compensatory mechanisms (e.g., activation of sympathetic nerves and the renin-angiotensin-aldosterone system) similar to what occurs during heart failure. The pain and anxiety associated with myocardial infarction further activates the sympathetic nervous system, which causes systemic vasoconstriction and cardiac stimulation (this explains why some patients become hypertensive and have tachycardia). While sympathetic activation helps to maintain arterial pressure, it also leads to a large increase in myocardial oxygen demand that can lead to greater myocardial hypoxia, enlarge the infarcted region, precipitate arrhythmias, and further impair cardiac function. Sympathetic activation is responsible for the diaphoresis (sweating) experienced by the patient. Renal hypoperfusion and sympathetic activation stimulate renin release, which leads to increased plasma levels of angiotensin II and aldosterone that enhance renal retention of sodium and water.