Dietary fish oil reduces the occurrence of early afterdepolarizations in pig ventricular myocytes

Ruijter, Hester M. den; Verkerk, Arie O.; Berecki, Géza; Bakker, Diane; Ginneken, A. C. G. Van; Coronel, Ruben

doi:10.1016/j.yjmcc.2006.08.001

Cited by 26 publications

(17 citation statements)

References 16 publications

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“…Therefore, the elevation of n-3 PUFAs helps to stabilize the enhanced excitability of partially depolarized cells in ischemic myocardium (34) and thus prevent arrhythmias. This hypothesis is supported by the recent finding that dietary fish oil reduces the occurrence of early afterdepolarizations in porcine ventricular myocytes (11). Although there is no clinical report on pericardial delivery of n-3 PUFAs, we believe that such an approach could be potentially beneficial to an ischemic heart and may prevent sudden cardiac death in the event of an infarction.…”

Section: Discussionsupporting

confidence: 63%

Pericardial delivery of omega-3 fatty acid: a novel approach to reducing myocardial infarct sizes and arrhythmias

Xiao¹,

Sigg²,

Ujhelyi³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Basic and clinical evidence suggests that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) decrease fatal arrhythmias and infarct sizes. This study investigated if pericardial delivery of n-3 PUFAs would protect the myocardium from ischemic damages and arrhythmias. Acute myocardial infarctions were induced in 23 pigs with either 45 min balloon inflations or clamp occlusions of the left anterior descending coronary arteries and 180 min reperfusion. Docosahexaenoic acid (C22:6n-3, DHA, 45 mg), one of the main n-3 PUFAs in fish oil, was infused within the pericardial space only during the 40-min stabilizing phase, 45 min ischemia and initial 5 min reperfusion. Hemodynamics and cardiac functions were very similar between the DHA-treated and control groups. However, DHA therapy significantly reduced infarct sizes from 56.8 +/- 4.9% for controls (n = 12) to 28.8 +/- 7.9% (P < 0.01) for DHA-treated animals (n = 11). Compared with controls, DHA-treated animals significantly decreased heart rates and reduced ventricular arrhythmia scores during ischemia. Furthermore, three (25%) control animals experienced eight episodes of ventricular fibrillation (VF), and two died subsequent to unsuccessful defibrillation. In contrast, only 1 (9%) of 11 DHA-treated pigs elicited one episode of VF that was successfully converted via defibrillation to normal rhythm; thus, mortality was reduced from 17% in the controls to 0% in the DHA-treated animals. These data demonstrate that pericardial infusion of n-3 PUFA DHA can significantly reduce both malignant arrhythmias and infarct sizes in a porcine infarct model. Pericardial administration of n-3 PUFAs could represent a novel approach to treating or preventing myocardial infarctions.

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Section: Discussionsupporting

confidence: 63%

Pericardial delivery of omega-3 fatty acid: a novel approach to reducing myocardial infarct sizes and arrhythmias

Xiao¹,

Sigg²,

Ujhelyi³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…The current necessary to induce extrasystoles was also increased by the perfusion of isolated rabbit hearts with n−3 PUFAs (concentration-dependent, EPA or DHA but not alpha-linolenic acid, ALA) (Dhein et al, 2005). Similar results were obtained in myocyte preparations (Kang & Leaf, 1994Kang & Leaf, 1996;Macleod et al, 1998;Den Ruijter et al, 2006;Verkerk et al, 2006;Berecki et al, 2007;Den Ruijter et al, 2008;Verkerk et al, 2009b;Den Ruijter et al, 2010;Milberg et al, 2011). For example, Leaf and co-workers extensively evaluated the acute application of n−3 PUFAs to cultures of neonatal rat ventricular myocytes (Kang & Leaf, 1994Kang & Leaf, 1996).…”

Section: Experimental Studies-animal Modelsmentioning

confidence: 69%

“…These investigators also used whole cell voltage clamp techniques to evaluate the effects of n−3 PUFAs on specific ion channels in either cardiac myocytes or on ion channels expressed in different cell lines (Xiao et al, , 1997(Xiao et al, , 1998(Xiao et al, , 2001(Xiao et al, , 2002(Xiao et al, , 2004b(Xiao et al, , 2006. These studies demonstrated that the acute administration of n−3 PUFAs has potent effects on many ion channels (Table 8) (Honoré et al, 1994;Xiao et al, 1995;Bogdanov et al, 1998;Hazama et al, 1998;Xiao et al, 1998;Leifert et al, 1999;Rodrigo et al, 1999;Singleton et al, 1999;Leifert et al, 2000Leifert et al, , 2001Doolan et al, 2002;Ferrier et al, 2002;Xiao et al, 2002;Judé et al, 2003;Dhein et al, 2005;Guizy et al, 2005;Den Ruijter et al, 2006;Verkerk et al, 2006;Xiao et al, 2006;Berecki et al, 2007;Den Ruijter et al, 2007;Szentandrássy et al, 2007;Den Ruijter et al, 2008;Dujardin et al, 2008;Verkerk et al, 2009b;Den Ruijter et al, 2010;Milberg et al, 2011;Moreno et al, 2012;van Borren et al, 2012;Zhao et al, 2012). These substances shift the inactivation threshold for sodium channels to a more negative potential (thereby decreasing cell excitability) …”

Section: Experimental Studies-animal Modelsmentioning

confidence: 99%

The effects of omega-3 polyunsaturated fatty acids on cardiac rhythm: A critical reassessment

Billman

2013

Pharmacology & Therapeutics

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“…For example, intracellular recordings in rat neonatal cardiomyocytes treated with EPA elicit: (1) more positive AP thresholds; (2) lower resting membrane potentials; (3) larger amounts of current needed to initiate APs; (4) slower phase 4 depolarizations; and (5) lower intrinsic beating frequencies [35,36]. Dietary fish oil has been shown to shorten AP durations and lower the plateau phase of APs in swine [32,37]. Recently, the first study in human cardiomyocytes showed that w3PUFAs likewise shortened the AP duration [38]; the study showed similar findings in rabbit cardiomyocytes.…”

Section: Action Potential Morphologymentioning

confidence: 99%

Electrophysiological Mechanisms of the Anti-arrhythmic Effects of Omega-3 Fatty Acids

Richardson

Iaizzo

Xiao

2010

J. of Cardiovasc. Trans. Res.

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Heart rhythm disorders, or arrhythmias, are a leading cause of morbidity and mortality worldwide. Omega-3 polyunsaturated fatty acids (ω3PUFAs), commonly found in fish oils and plant seeds, have recently emerged as potential anti-arrhythmic agents. The purpose of this review is to summarize the electrophysiological basis of the anti-arrhythmic properties of ω3PUFAs from clinical, animal, and cellular research. Evidence of the anti-arrhythmic effects of ω3PUFAs originated from epidemiological studies that correlated a low incidence of sudden cardiac death with high dietary ω3PUFA intake. Subsequently, multiple clinical trials have confirmed the therapeutic effects of ω3PUFAs in preventing sudden cardiac death and multiple other arrhythmia-related disorders. This has led basic scientists to investigate the effects of ω3PUFAs on several ion channels including sodium, potassium, and calcium channels, as well as Na/Ca exchangers. Therefore, ω3PUFAs may hold promise as safe and effective anti-arrhythmic agents. Nevertheless, further research is needed in areas such as: (1) identifying which form(s) of ω3PUFAs (i.e., phospholipid, triglyceride, or free) is (are) responsible for anti-arrhythmic actions; and (2) developing reproducible methods for delivery so that the appropriate form and concentration may be present at the target site to prevent and treat arrhythmias.

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Dietary fish oil reduces the occurrence of early afterdepolarizations in pig ventricular myocytes

Cited by 26 publications

References 16 publications

Pericardial delivery of omega-3 fatty acid: a novel approach to reducing myocardial infarct sizes and arrhythmias

Pericardial delivery of omega-3 fatty acid: a novel approach to reducing myocardial infarct sizes and arrhythmias

The effects of omega-3 polyunsaturated fatty acids on cardiac rhythm: A critical reassessment

Electrophysiological Mechanisms of the Anti-arrhythmic Effects of Omega-3 Fatty Acids

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