Why is atropine (antimuscarinic agent) ineffective in heart transplant patients with denervated hearts?

From the Guidelines

Atropine is ineffective for heart transplant patients due to the denervation of the heart, which results in a lack of vagal innervation, making it an inappropriate choice for treating bradycardia in this population. The mechanism of action of atropine involves blocking the parasympathetic effects of acetylcholine on the heart by inhibiting the vagus nerve's action at muscarinic receptors 1. However, in a transplanted heart, the vagal nerve connections are severed during the transplantation procedure, resulting in a heart that operates without direct parasympathetic control.

Some key points to consider when treating bradycardia in heart transplant patients include:

• The lack of vagal tone, which leads to a resting heart rate of 90-110 beats per minute due to the reliance on circulating catecholamines for heart rate regulation 1
• The potential for atropine to cause paradoxical heart block or sinus arrest in heart transplant patients, as seen in a study of 25 patients who underwent heart transplant 1
• The limited evidence for parasympathetic reinnervation after orthotopic heart transplant, with sympathetic reinnervation being more common 1

When treating bradycardia in heart transplant patients, direct-acting beta-agonists like isoproterenol or epinephrine would be more appropriate choices than atropine, as they can increase heart rate and improve symptoms without relying on vagal tone 1. Additionally, other medications like aminophylline or theophylline may be considered, as they have shown beneficial effects on heart rate and sinus node function in heart transplant recipients 1.

From the FDA Drug Label

Atropine-induced parasympathetic inhibition may be preceded by a transient phase of stimulation, especially on the heart where small doses first slow the rate before characteristic tachycardia develops due to paralysis of vagal control Atropine exerts a more potent and prolonged effect on heart, intestine and bronchial muscle than scopolamine, but its action on the iris, ciliary body and certain secretory glands is weaker than that of scopolamine. Adequate doses of atropine abolish various types of reflex vagal cardiac slowing or asystole The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus.

Atropine may be ineffective for heart transplant patient populations because denervated hearts (such as those in heart transplant patients) do not respond to atropine in the same way as innervated hearts. The drug label does not directly address the use of atropine in heart transplant patients, but it can be inferred that atropine's effectiveness may be reduced in this population due to the lack of vagal control in denervated hearts 2.

• Key points:
  • Atropine's action on the heart is primarily through paralysis of vagal control
  • Denervated hearts may not respond to atropine in the same way as innervated hearts
  • The drug label does not provide direct information on the use of atropine in heart transplant patients

From the Research

Ineffectiveness of Atropine in Heart Transplant Patients

• Atropine may be ineffective in heart transplant patients due to the denervated state of the heart, which can lead to unpredictable responses to the medication 3, 4.
• The denervated heart may not respond normally to atropine, resulting in paradoxical effects such as atrioventricular block or sinus arrest 3, 4.
• Studies have shown that atropine can cause high-degree atrioventricular block in patients after heart transplantation, highlighting the need for caution when using this medication in these patients 3, 4.

Factors Contributing to Ineffectiveness

• The lack of parasympathetic reinnervation in the transplanted heart may contribute to the ineffectiveness of atropine, as the medication relies on cholinergic cardiac stimulation to exert its effect 5.
• The dose of atropine may not be a predicting factor for its effectiveness or safety in heart transplant patients, as adverse effects have been observed at various doses 4.
• Resting heart rate may be a predictor of the need for atropine during dobutamine stress echocardiography, but it is not a reliable indicator of the medication's effectiveness 5.

Safety Concerns

• The administration of atropine during dobutamine stress echocardiography in heart transplant patients has been associated with adverse events, including complete heart block and sinus arrest 6.
• Patients should be closely monitored for these adverse events during and after the procedure, highlighting the need for caution when using atropine in this population 6.