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(Circulation. 2008;118:e70.)
© 2008 American Heart Association, Inc.

Correspondence

Response to Letter Regarding Article "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; Jan W.T. Fiolet, PhD; Ruben Coronel, MD, PhD

Department of Experimental Cardiology, Center for Heart Failure Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

Nicolaas de Jonge, MD, PhD

Department of Cardiology Heart Lung Center University Medical Center Utrecht Utrecht, the Netherlands

Ingeborg A. Brouwer, PhD

Top Institute Food and Nutrition, Wageningen, the Netherlands

We thank Drs Pignier and LeGrand for their interest in our work.¹ In their letter, Drs Pignier and LeGrand express their belief that inhibition of the persistent component of the sodium current (I_Na,P) constitutes a key mechanism of the antiarrhythmic properties of 3-polyunsaturated fatty acids in heart failure in our study,¹ a factor not mentioned by us. We agree that persistent I_Na,P, if present, may contribute to Ca²⁺ overload-induced arrhythmogenesis in heart failure. In our model of heart failure, however, elevated [Na⁺]_i originated from increased activity of the Na⁺/H⁺ exchanger, leading to [Ca²⁺]_i overload through the Na⁺/Ca²⁺ exchanger; I_Na,P was absent.² We cannot exclude I_Na,P in human myocytes, although similarity of the response to 3-polyunsaturated fatty acids makes species differences less probable. In addition, reductions in [Ca²⁺]_i levels after application of 3-polyunsaturated fatty acids have been observed in isolated myocytes from both healthy and diseased hearts^1,3,4 and are therefore likely independent of I_Na,P.

The antiarrhythmic effect of 3-polyunsaturated fatty acids in our study can be explained by reduced action potential shortening and [Ca²⁺]_i elevation in response to noradrenalin,¹ as well as by a reduction of L-type Ca²⁺ current and Na⁺/Ca²⁺ exchange current in combination with inhibition of Ca²⁺ release channels of the sarcoplasmic reticulum.^3–5 Therefore, we excluded the possibility that the antiarrhythmic mechanism of 3-polyunsaturated fatty acids is related to inhibition of I_Na,P, at least in the rabbit model of heart failure.

	Acknowledgments

 
Disclosures

None.

	References

Top References

 

1. den Ruijter HM, Berecki G, Verkerk AO, Bakker D, Baartscheer A, Schumacher CA, Belterman CNW, de Jonge N, Fiolet JWT, Brower IA, Coronel R. Acute administration of fish oil inhibits triggered activity in isolated myocytes from rabbits and patients with heart failure. Circulation. 2008; 117: 536–544.[Abstract/Free Full Text]
   
2. Baartscheer A, Hardziyenka M, Schumacher C, Belterman CN, van Borren MMGJ, Verkerk AO, Coronel R, Fiolet JWT. Chronic inhibition of the Na^+/H⁺-exchanger causes regression of hypertrophy, heart failure, and ionic and electrophysiological remodelling. Br J Pharmacol. In press.
   
3. Den Ruijter HM, Berecki G, Opthof T, Verkerk AO, Zock PL, Coronel R. Pro- and antiarrhythmic properties of a diet rich in fish oil. Cardiovasc Res. 2007; 73: 316–325.[Abstract/Free Full Text]
   
4. Negretti N, Perez MR, Walker D, O'Neill SC. Inhibition of sarcoplasmic reticulum function by polyunsaturated fatty acids in intact, isolated myocytes from rat ventricular muscle. J Physiol. 2000; 523: 367–375.[Abstract/Free Full Text]
   
5. Xiao YF, Gomez AM, Morgan JP, Lederer WJ, Leaf A. Suppression of voltage-gated L-type Ca²⁺ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes. Proc Natl Acad Sci U S A. 1997; 94: 4182–4187.[Abstract/Free Full Text]
   

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