How does epinephrine (EPi) cause ischemia in patients with ischemic heart disease?

How Epinephrine Causes Ischemia in Patients with Ischemic Heart Disease

Epinephrine causes myocardial ischemia in patients with ischemic heart disease through multiple mechanisms: β-adrenergic effects that dramatically increase myocardial oxygen demand while simultaneously reducing subendocardial perfusion, α-adrenergic effects that cause coronary vasoconstriction (particularly at the microvascular level), and proarrhythmic effects that further compromise cardiac function. 1

Primary Mechanisms of Epinephrine-Induced Ischemia

Increased Myocardial Oxygen Demand (β-Adrenergic Effects)

The β-adrenergic effects of epinephrine are the primary driver of ischemia through a dramatic increase in cardiac work and oxygen consumption. 1

• Epinephrine accelerates heart rate, improves cardiac conduction, stimulates the rate of relaxation, and reinforces systolic efficiency, resulting in increased cardiac output at the cost of dramatically increased cardiac work and oxygen consumption 1
• β-adrenergic stimulation increases myocardial oxygen demand (MVO2) through its effects on both heart rate and contractility 2
• In patients with coronary artery disease, epinephrine infusions maintained hemodynamics and ventricular pump function but induced myocardial ischemia, with ischemic thresholds ranging from 652 to 3362 pg/ml 3

Reduced Myocardial Oxygen Supply (α-Adrenergic Effects)

The α-adrenergic effects of epinephrine reduce oxygen delivery to the myocardium through vasoconstriction at multiple levels. 1

• α-adrenergic effects cause vasoconstriction at the microvascular level, resulting in greater tissue ischemia 1
• β-adrenergic effects may reduce subendocardial perfusion, creating a supply-demand mismatch 1
• Epinephrine can induce coronary vasospasm, which is particularly dangerous in patients with underlying coronary artery disease who have flow-limiting luminal irregularities 4

Proarrhythmic Effects

Epinephrine increases the risk of potentially lethal cardiac arrhythmias, which further compromise myocardial perfusion and increase oxygen demand. 5, 6

• Epinephrine may induce cardiac arrhythmias and myocardial ischemia in patients, especially those with coronary artery disease or cardiomyopathy 5
• Arrhythmias, including fatal ventricular fibrillation, have occurred particularly in patients with underlying organic heart disease 6
• Epinephrine may be associated with a higher risk of tachycardia and arrhythmias compared to norepinephrine 1

Clinical Manifestations and Evidence

Documented Cases of Epinephrine-Induced Ischemia

• Accidental intravenous administration of high-concentration epinephrine resulted in significant ischemic ECG changes, transiently raised cardiac enzymes, reduced left ventricular systolic function, pulmonary edema, and pulmonary hemorrhage 7
• A case report documented epinephrine-induced coronary artery vasospasm following anaphylaxis treatment that exacerbated a type 1 ST-segment elevation myocardial infarction in a patient with undiagnosed coronary artery disease 4
• Following epinephrine administration for anaphylaxis, a patient developed ST-segment depression on ECG within 30 minutes, with symptoms resolving after nitroglycerin administration, suggesting coronary artery spasm 8

Comparative Effects in Coronary Disease vs. Normal Patients

• In patients with coronary artery disease compared to those with normal coronary anatomy, epinephrine infusions resulted in more frequent ventricular arrhythmias (55% vs. 25%), chest pain (50% vs. 13%), and ischemic ECG changes (73% vs. 13%) 3
• Contractility increased significantly less and end-systolic volume decreased significantly less in patients with coronary artery disease compared to normal subjects 3

Critical Clinical Considerations

Risk Factors and Contraindications

Patients with coronary artery disease face substantially higher risk of epinephrine-induced ischemia and require vigilant cardiac monitoring. 4, 8

• The FDA label warns that epinephrine may induce cardiac arrhythmias and myocardial ischemia in patients, especially those with coronary artery disease or cardiomyopathy 5
• Angina may occur in patients with coronary artery disease following epinephrine administration 6
• Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease 6

Sympathomimetic Toxicity Context

Epinephrine and other sympathomimetic agents are recognized causes of myocardial ischemia through both increased oxygen demand and decreased oxygen supply mechanisms. 1

• The 2012 ACC/AHA guidelines list sympathomimetic toxicity (including cocaine use and pheochromocytoma) under both "Increased Oxygen Demand" and "Decreased Oxygen Supply" categories for conditions provoking or exacerbating ischemia 1
• Cocaine abuse and sympathomimetic toxicity are recognized as causes of increased myocardial oxygen demand 1

Monitoring and Management Implications

• Physicians should observe patients closely following epinephrine administration, as the treatments for anaphylaxis and myocardial ischemia differ 8
• Vigilant cardiac monitoring and management of potentially life-threatening cardiac complications is essential when administering epinephrine, especially in patients with risk factors for coronary artery disease 4
• High plasma levels of epinephrine result from sympathoadrenal activation and may contribute to electrical instability of the myocardium and generation of dysrhythmias 9