Response to Letter Regarding Article “Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure”
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 (INa,P) constitutes a key mechanism of the antiarrhythmic properties of ω3-polyunsaturated fatty acids in heart failure in our study,1 a factor not mentioned by us. We agree that persistent INa,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; INa,P was absent.2 We cannot exclude INa,P in human myocytes, although similarity of the response to ω3-polyunsaturated fatty acids makes species differences less probable. In addition, reductions in [Ca2+]i levels after application of ω3-polyunsaturated fatty acids have been observed in isolated myocytes from both healthy and diseased hearts1,3,4 and are therefore likely independent of INa,P.
The antiarrhythmic effect of ω3-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 ω3-polyunsaturated fatty acids is related to inhibition of INa,P, at least in the rabbit model of heart failure.
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.
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.
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.
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.