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Heparin Oligosaccharides Have Antiarrhythmic Effect by Accelerating the Sodium-Calcium Exchanger

Carlos M G de Godoy1, Ênio R Vasques2,3, Afonso Caricati-Neto4

  • 1Institute of Science and Technology, Universidade Federal de São Paulo, São Paulo, Brazil.

Frontiers in Cardiovascular Medicine
|June 23, 2018
PubMed

Insights

Heparin oligosaccharides, like trisulfated heparin disaccharide (TD), show antiarrhythmic effects by accelerating the Na+/Ca2+ exchanger (NCX) activity. These compounds prevent calcium overload-induced arrhythmias and reduce mortality in heart conditions.

Area of Science:

  • Cardiovascular Pharmacology
  • Cardiac Electrophysiology
  • Drug Discovery

Background:

  • The Na+/Ca2+ exchanger (NCX) plays a crucial role in cardiac rhythm regulation.
  • Blocking NCX is a method to study its involvement in arrhythmogenesis.
  • Heparin derivatives, such as trisulfated heparin disaccharide (TD) and Low Molecular Weight Heparins (LMWHs), can modulate NCX activity.

Purpose of the Study:

  • To investigate the antiarrhythmic potential of heparin oligosaccharides.
  • To elucidate the mechanism of action of these compounds on NCX activity.
  • To evaluate their efficacy in preventing and treating cardiac arrhythmias.

Main Methods:

  • Patch-clamp electrophysiology to measure NCX current in rat cardiomyocytes.
  • Assessment of intracellular calcium transients.
  • Induction and evaluation of arrhythmias in isolated rat atria and in vivo rat models.
  • Pharmacological inhibition of NCX using KB-R7943.

Main Results:

  • Enoxaparin and ardeparin reduced intracellular Ca2+ concentration and abolished arrhythmia induction in isolated atria.
  • The antiarrhythmic effects of enoxaparin and ardeparin were reversed by the NCX antagonist KB-R7943.
  • In vivo, TD administration significantly prevented reperfusion-induced arrhythmias and reduced mortality.
  • Mechanistically, TD was shown to increase the forward mode NCX current.

Conclusions:

  • Heparin oligosaccharides exhibit significant antiarrhythmic properties.
  • Their mechanism involves accelerating the forward mode of the Na+/Ca2+ exchanger during calcium overload.
  • These findings suggest heparin oligosaccharides represent a novel class of antiarrhythmic agents.

Keywords:
arrhythmiacalcium overloadlow molecular weight heparinsodium-calcium exchangertrisulfated heparin disaccharide

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