Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure

• Published in: Circulation (New York, N.Y.) Vol. 117; no. 4; pp. 536 - 544
• Main Authors: DEN RUIJTER, Hester M, BERECKI, Géza, CORONEL, Ruben, VERKERK, Arie O, BAKKER, Diane, BAARTSCHEER, Antonius, SCHUMACHER, Cees A, BELTERMAN, Charly N. W, DE JONGE, Nicolaas, FIOLET, Jan W. T, BROUWER, Ingeborg A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 29.01.2008
• Subjects: Action Potentials; Animals; Arrhythmias, Cardiac - prevention & control; Biological and medical sciences; Blood and lymphatic vessels; Calcium - analysis; Cardiology. Vascular system; Cells, Cultured; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Unsaturated - pharmacology; Fish Oils - pharmacology; Fundamental and applied biological sciences. Psychology; General aspects; Heart Failure - pathology; Humans; Medical sciences; Membrane Potentials; Muscle Cells - cytology; Muscle Cells - drug effects; Norepinephrine - pharmacology; Rabbits; Vertebrates: cardiovascular system; Human; Heart failure; Calcium; Arrhythmia; fatty acids; Electrophysiology; Rabbit; Cardiovascular disease; Lagomorpha; Inorganic element; Fish oil; Myocyte; Vertebrata; Mammalia; Heart disease; Animal
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.107.733329

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. 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. 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.