Premature Ventricular Contraction - Molecular Basis

Molecular Basis

There are a number of different molecular explanations for PVCs. One explanation is most basically due to an increased amount of cyclic AMP(cAMP) in the ventricular cardiac myocytes leading to increased flow of calcium ions into the cell. This may happen for the following reasons:

• Activation of the sympathetic nervous system, due to anxiety and/or physiological stress, for example hypovolemia caused by dehydration or hemorrhage. This activation can cause a release of catecholamines such as epinephrine (adrenaline) which can bind to beta-1 adrenergic receptor (β₁ receptors) on cardiac myocytes, activating a type of guanosine nucleotide-binding protein called G_s protein. This type of protein stimulates the production of cAMP, ultimately increasing the flow of calcium ions from the extracellular space and from the sarcoplasmic reticulum into the cytosol.
  This has the effect of (1) increasing the strength of contraction (inotropy) and (2) depolarizing the myocyte more rapidly (chronotropy). The ventricular myocytes are therefore more irritable than usual, and may depolarize spontaneously before the SA node depolarizes. Other sympathomimetic molecules such as amphetamines and cocaine will also cause this effect.
• Phosphodiesterase inhibitors such as caffeine directly affect the G-coupled signal transduction cascade by inhibiting the enzyme that catalyzes the breakdown of cAMP, again leading to the increased concentration of calcium ions in the cytosol.

Potassium ion concentrations are a major determinant in the magnitude of the electrochemical potential of cells, and hypokalemia makes it more likely that cells will depolarize spontaneously. Hypercalcemia has a similar effect, although clinically it is of less concern. Magnesium ions affect the flow of calcium ions, and they affect the function of the Na+/K+ ATPase, and are necessary for maintaining potassium levels. Hypomagnesemia therefore also makes spontaneous depolarization more likely.

Existing damage to the myocardium can also provoke PVCs. The myocardial scarring that occurs in myocardial infarction and also in the surgical repair of congenital heart disease can disrupt the conduction system of the heart and may also irritate surrounding viable ventricular myocytes, make them more likely to depolarize spontaneously. Inflammation of the myocardium (as occurs in myocarditis) and systemic inflammation cause surges of cytokines, which can affect the electrical properties of myocytes and may be ultimately responsible for causing irritability of myocytes.