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PDE4 in the human heart - major player or little helper?

Thomas Eschenhagen1

  • 1Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg Eppendorf, Germany. t.eschenhagen@uke.uni-hamburg.de

British Journal of Pharmacology
|March 16, 2013
PubMed

Insights

Phosphodiesterase (PDE) inhibitors can increase heart contractility but may cause arrhythmias. PDE4 inhibitors did not affect human ventricular contractility, suggesting a lower arrhythmogenic risk in the ventricle compared to the atria.

Area of Science:

  • Cardiovascular Pharmacology
  • Molecular Cardiology

Background:

  • Phosphodiesterases (PDEs) regulate cardiac function by degrading cyclic AMP (cAMP).
  • PDE inhibitors are used as positive inotropes, but can cause adverse effects like arrhythmias.
  • PDE3 was historically considered the primary cardiac PDE isoform, but PDE4's role is increasingly recognized.

Purpose of the Study:

  • To investigate the role of PDE4 in human ventricular contractility.
  • To assess the arrhythmogenic potential of PDE4 inhibition in the human ventricle.

Main Methods:

  • Experiments utilized ventricular trabeculae from explanted human hearts.
  • The effects of PDE3 and PDE4 inhibitors on beta-adrenoceptor stimulation were measured.

Main Results:

  • The PDE4 inhibitor rolipram did not alter the positive inotropic effects of beta1- or beta2-adrenoceptor stimulation in human ventricular trabeculae.
  • This suggests PDE4 does not significantly modulate contractility in the human ventricle.

Conclusions:

  • PDE4 inhibition does not appear to enhance catecholamine-induced contractility in the human ventricle.
  • This finding is reassuring regarding the arrhythmogenic risk of PDE4 inhibitors in the ventricle, a critical region for cardiac events.
Abstract

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