Catecholamines like adrenaline and noradrenaline are hormones released by the adrenal glands in response to stress. They prepare the body for the “fight or flight” response by increasing heart rate, blood pressure, and blood flow to muscles. However, chronic elevation of catecholamines can potentially lead to heart failure. In this article, we will examine the mechanism by which catecholamines affect the heart and discuss the evidence on whether they can cause heart failure.
What are catecholamines?
Catecholamines are hormones produced in the adrenal glands that include:
- Adrenaline (epinephrine)
- Noradrenaline (norepinephrine)
- Dopamine
They are released into the bloodstream in response to any type of stress – physical, emotional, or psychological. The main actions of catecholamines include:
- Increasing heart rate and contraction force
- Dilating blood vessels in skeletal muscles
- Constricting blood vessels in the skin and visceral organs
- Dilating the airways of the lungs
- Increasing blood glucose levels
This helps divert blood flow to the muscles and vital organs to prepare the body for “fight or flight.” However, chronic elevation of catecholamines can be detrimental.
How do catecholamines affect the heart?
Catecholamines like adrenaline act on adrenergic receptors in the heart. The main effects are:
- Increasing heart rate (chronotropy)
- Increasing the force of heart contraction (inotropy)
- Increasing conduction velocity through the heart (dromotropy)
This increases cardiac output and blood delivery to muscles and vital organs. However, long-term exposure can lead to:
- Myocardial hypertrophy – thickening of heart muscle
- Fibrosis – scarring of heart tissue
- Cell death
These effects on the myocardium can reduce cardiac function over time and potentially lead to heart failure.
Key mechanisms
Several mechanisms have been proposed for catecholamine-induced heart damage:
- Calcium overload – Catecholamines increase calcium entry into cardiac cells. Excess calcium can damage cell structures.
- Oxidative stress – Catecholamines increase reactive oxygen species which damage proteins, lipids, DNA.
- Inflammation – Stimulate local inflammation and inflammatory cytokines.
- Apoptosis – Programmed cell death pathways are activated.
- Hypertrophy – Pathological growth of heart muscle cells.
- Ischemia – Catecholamines constrict small blood vessels in the heart which can cause inadequate oxygen supply.
Through these mechanisms, chronic catecholamine elevation alters the structure and function of the heart. This can ultimately lead to reduced contraction and pumping ability, characteristic of heart failure.
Animal studies
Numerous animal studies have demonstrated that sustained exposure to high levels of catecholamines can induce myocardial damage.
For example, chronic infusion of norepinephrine in rats results in myocardial lesions, inflammatory infiltrates, hypertrophy, and fibrosis. Rats exposed to stress by restraint or electric shocks also show adrenaline-dependent myocardial damage.
Interestingly, rats pre-treated with beta-blockers like propranolol show significantly less catecholamine-mediated heart injury from stress. This indicates that blockade of adrenaline’s beta-adrenergic effects can be protective.
Multiple studies confirm adrenaline’s role by showing reduced cardiomyopathy when rats are pre-treated with adrenal medullectomy to prevent adrenaline release.
Overall, animal models provide convincing evidence that chronically elevated catecholamines, especially adrenaline, can cause structural changes in the heart leading to heart failure.
Human studies
In humans, direct evidence linking long-term catecholamine exposure to heart disease is limited due to ethical constraints on such studies.
However, certain human conditions are associated with high catecholamine states and provide insight:
Pheochromocytoma
These are tumors of the adrenal gland that over-secrete catecholamines. The sustained catecholamine excess causes:
- Hypertension
- Myocardial injury – heart failure in up to 23% of cases
- Reversal of cardiomyopathy after tumor resection in many patients
This strongly supports the role of chronic high catecholamines in causing heart problems.
Stress cardiomyopathy
Also called Broken Heart Syndrome or Takotsubo cardiomyopathy. This typically occurs after severe physical or emotional stress and involves temporary heart muscle weakness.
Catecholamines released during the stress are believed to be the primary cause. Supporting evidence:
- High catecholamine blood levels during episodes
- Stress triggers like death of a loved one
- Similar appearance to catecholamine cardiotoxicity in animal models
- Reversible after normalization of catecholamine levels
Cardiotoxicity of sympathomimetic drugs
Drugs like amphetamines and cocaine that stimulate catecholamine release and adrenergic signaling can also damage the heart:
- Chronic use linked to myocardial fibrosis and dilated cardiomyopathy
- Catecholamine excess from the drugs mediates cardiotoxicity
Chronic stress
In patients with chronic mental stress and anxiety, studies show elevated levels of plasma catecholamines. Stress-induced cardiomyopathy is also well documented.
Although a direct causal link is difficult to establish, chronic stress likely increases heart failure risk via catecholamine-induced myocardial damage.
Treatment
If catecholamine excess is contributing to heart problems, the most direct treatment is to lower catecholamine levels. This can be achieved with:
- Beta blockers – block the cardiac effects of catecholamines
- Central sympatholytics – reduce catecholamine synthesis and release
- Alpha-2 agonists like clonidine suppress norepinephrine release
- Tumor resection in pheochromocytoma
Lifestyle changes like stress reduction techniques, exercise, and mindfulness may also be beneficial. Preventing surges in catecholamine levels from stress can mitigate their cardiotoxic effects.
Conclusion
Evidence from animal studies clearly demonstrates that chronically elevated catecholamines like adrenaline can damage the heart and lead to heart failure.
In humans, catecholamine excess in conditions like pheochromocytoma and chronic stress is associated with myocardial injury and cardiomyopathy.
Exact mechanisms are complex and multifactorial but involve calcium overload, oxidative damage, inflammation, and cell death pathways.
Lowering catecholamine levels provides the most direct treatment approach. Lifestyle changes to prevent surges during stress are also prudent.
In summary, prolonged elevation of circulating catecholamines appears sufficient to cause detrimental structural changes in the heart and should be considered a potential cause of heart failure.
