Published Online
on January 14, 2008

A more recent version of this article appeared on January 29, 2008

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Submitted on August 9, 2007
Accepted on November 17, 2007

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

Hester M. Den Ruijter PhD^*, Géza Berecki PhD, Arie O. Verkerk PhD, Diane Bakker RA, Antonius Baartscheer PhD, Cees A. Schumacher RA, Charly N.W. Belterman RA, Nicolaas de Jonge MD, PhD, Jan W.T. Fiolet PhD, Ingeborg A. Brouwer PhD, and Ruben Coronel MD, PhD

From the Departments of Experimental Cardiology (H.M.D.R., G.B., A.O.V., D.B., A.B., C.A.S., C.N.W.B., J.W.T.F., R.C.), and Physiology (A.O.V.), Center for Heart Failure Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Cardiology (N.d.J.), Heart Lung Center, University Medical Center Utrecht, Utrecht, the Netherlands; and Top Institute Food and Nutrition (I.A.B.), Wageningen, the Netherlands.

^* To whom correspondence should be addressed. E-mail: h.m.denruijter{at}amc.uva.nl.

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 3-polyunsaturated fatty acids (3-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), -9 monounsaturated fatty acid oleic acid (20 µmol/L), or 3-PUFAs (docosahexaenoic acid or eicosapentaenoic acid 20 µmol/L). 3-PUFAs shortened the action potential at low stimulation frequencies and caused an 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. 3-PUFAs abolished triggered activity and reduced the number of delayed afterdepolarizations and calcium aftertransients compared with control and oleic acid. 3-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.

Conclusion—Superfusion with 3-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.

Key words: arrhythmia • calcium • electrophysiology • fatty acids • heart failure

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Clinical Summaries
Circulation 2008 117: 453-455. [Full Text]

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				C. Pignier and B. Le Grand Letter by Pignier and Le Grand Regarding Article "Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure" Circulation, July 15, 2008; 118(3): e69 - e69. [Full Text] [PDF]

				H. M. den Ruijter, G. Berecki, A. O. Verkerk, D. Bakker, A. Baartscheer, C. A. Schumacher, C. N.W. Belterman, J. W.T. Fiolet, R. Coronel, N. de Jonge, et al. Response to Letter Regarding Article "Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure" Circulation, July 15, 2008; 118(3): e70 - e70. [Full Text] [PDF]