Acute administration of fish oil inhibits triggered activity in isolated myocytes from rabbits and patients with heart failure.
BACKGROUND
Fish oil reduces sudden death in patients with prior myocardial infarction. Sudden death in heart failure may be due to triggered activity based on disturbed calcium handling. We hypothesized that superfusion with omega3-polyunsaturated fatty acids (omega3-PUFAs) from fish inhibits triggered activity in heart failure.


RESULTS
Ventricular myocytes were isolated from explanted hearts of rabbits with volume- and pressure-overload-induced heart failure and of patients with end-stage heart failure. Membrane potentials (patch-clamp technique) and intracellular calcium (indo-1 fluorescence) were recorded after 5 minutes of superfusion with Tyrode's solution (control), omega-9 monounsaturated fatty acid oleic acid (20 micromol/L), or omega3-PUFAs (docosahexaenoic acid or eicosapentaenoic acid 20 micromol/L). omega3-PUFAs shortened the action potential at low stimulation frequencies and caused an approximately 25% decrease in diastolic and systolic calcium (all P<0.05). Subsequently, noradrenalin and rapid pacing were used to evoke triggered activity, delayed afterdepolarizations, and calcium aftertransients. omega3-PUFAs abolished triggered activity and reduced the number of delayed afterdepolarizations and calcium aftertransients compared with control and oleic acid. Omega3-PUFAs reduced action potential shortening and intracellular calcium elevation in response to noradrenalin. Results from human myocytes were in accordance with the findings obtained in rabbit myocytes.


CONCLUSIONS
Superfusion with omega3-PUFAs from fish inhibits triggered arrhythmias in myocytes from rabbits and patients with heart failure by lowering intracellular calcium and reducing the response to noradrenalin.
Den Ruijter
Hester M
HM
Department of Experimental Cardiology, Center for Heart Failure Research, Academic Medical Center, Room K2-113, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. h.m.denruijter@amc.uva.nl
Berecki
Géza
G
Verkerk
Arie O
AO
Bakker
Diane
D
Baartscheer
Antonius
A
Schumacher
Cees A
CA
Belterman
Charly N W
CN
de Jonge
Nicolaas
N
Fiolet
Jan W T
JW
Brouwer
Ingeborg A
IA
Coronel
Ruben
R
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology*; D006333:Heart Failure / Q000473:pathology*; D006801:Humans; D008564:Membrane Potentials; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D002118:Calcium; D009638:Norepinephrine