Basic Science

Peter Alter, Prof, MD
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Tobias Glück, MD
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For years treatment with omega-3 highly unsaturated fatty acids (HUFA) for cardiological indications was discussed. A bunch of clinical data exists for coronary artery disease, heart failure of various origin, sudden cardiac death, ventricular arrhythmias and atrial fibrillation. But the clinical studies still report divergent findings and indecisive benefit. In this instance the endogenous metabolism of omega-3 fatty acids was underrated in the past.

A better pathophysiological understanding of mechanisms is needed to finally evaluate the potential benefits of omega-3 therapy. Not only oral administration of marine omega-3 HUFA e.g. in form of fish oil, but also regulation of myocardial fatty acid homeostasis is suggested.

Our current article in Vascular Pharmacology reviews the major studies on basic pathophysiological mechanisms and clinical treatment trials. It also summarizes our understanding and ideas of endogenous omega-3 HUFA metabolism.

  • Heart failure: Wall stress determines systolic and diastolic function (see LINK “Heart imaging & wall stress”). We found an increased ventricular wall stress to be involved in the local myocardial as well as in the hepatic fatty acid metabolism. Furthermore in patients with LV dilatation a “HUFA deficiency” was reported earlier.
  • Endogenous metabolism: We suggest betaoxidation as one potential target to increase endogenous myocardial omega-3 concentrations.
  • Arrhythmias: Searching for determinants of atrial fibrillation the myocardial omega-3 HUFA concentrations should be taken into account. We recently found significantly reduced levels of the antiarrytmic DHA in atrial compared with ventricular myocardium.
Marine omega-3 highly unsaturated fatty acids: From mechanisms to clinical implications in heart failure and arrhythmias. T Glück, P Alter – Vascular pharmacology, 2016

The figure demonstrates the interrelation between the vicious circle of heart failure including left ventricular dilatation and increased wall stress and the important clinical correlate of sudden cardiac death by ventricular arrythmias. Omega-3 highly unsaturated fatty acids in the microenvironment of ion channels lead to allosteric changes and increase the electrical stability of the cardiomyocyte.