Abstract
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. METHODS AND
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.
- /&/
- acids,
- action
- analysis;
- animals;
- arrhythmias,
- calcium,
- cardiac,
- cells,
- control;
- cultured;
- cytology/drug
- effects;
- failure,
- fatty
- fish
- heart
- humans;
- membrane
- muscle
- norepinephrine,
- oils,
- omega-3,
- pathology;
- pharmacology;
- potentials;
- prevention
- rabbits
- unsaturated,
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