Omega-3 polyunsaturated fatty acids prevent atrial fibrillation associated with heart failure but not atrial tachycardia remodeling
Omega-3 polyunsaturated fatty acids prevent atrial fibrillation associated with heart failure but not atrial tachycardia remodeling
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DOI：
10.1161/circulationaha.107.704759
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发表时间：
2007-11-06
期刊：
影响因子：
37.8
通讯作者：
Nattel, Stanley
中科院分区：
文献类型：
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作者：
Sakabe, Masao;Shiroshita-Takeshita, Akiko;Nattel, Stanley
背景-有流行病学证据表明，omega-3多不饱和脂肪酸(PUFAs)可降低心房颤动(AF)的风险，但临床数据相互矛盾。本研究在实验模型上评价了多不饱和脂肪酸对房颤的影响。方法和结果-我们研究了口服多不饱和脂肪酸对两种实验性房颤的影响：房性心动过速(400次/分，持续1周)诱发的电重构和充血性心力衰竭相关的结构重建(由室性心动过速(240次/分钟，持续2周)引起)。PUFA预处理不能直接改变心房有效不应期(128+/-6对127+/-2ms；所有有效不应期均为300ms)或阵发性起搏诱发的房颤持续时间(5+/-4对34+/-18s)。房性心动过速犬的不应期(73+/-6ms)比假手术组(119+/-5ms)短，房颤持续时间(1185+/-300s)长(20+/-11s；P<；0.01)。多不饱和脂肪酸对不应期(77+/-8ms)或房颤持续时间(1128+/-412秒)的房性心动过速无明显影响。多不饱和脂肪酸可抑制由室性心动过速引起的房颤持续时间的延长(952+/-221vs318+/-249秒；P<；0.001)，并减轻与充血性心力衰竭相关的心房纤维化(从19.2+/-1.1%至5.8+/-1.0%；P<；0.001)和传导异常。多不饱和脂肪酸还可减轻室性心动过速引起的血流动力学障碍(例如，左心室舒张末和左房内压分别从12.2±/-0.5和11.4+/-0.6 mm Hg降至6.4+/-0.5和7.0+/-0.8 mm Hg；P<；0.01)和丝裂原活化蛋白激酶的磷酸化(细胞外信号相关和P38激酶)。结论：多不饱和脂肪酸抑制充血性心力衰竭所致的心房结构重构和房颤的发生，但不影响房性心动过速所致的电重构。多不饱和脂肪酸对结构重塑的有利作用可能与阻止丝裂原活化蛋白激酶激活有关，这可能有助于其临床抗房颤的潜力。
Background - There is epidemiological evidence that omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of atrial fibrillation (AF), but clinical data are conflicting. The present study assessed the effects of PUFA on AF in experimental models.Methods and Results - We studied the effects of oral PUFA supplements in 2 experimental AF paradigms: electrical remodeling induced by atrial tachypacing ( 400 bpm for 1 week) and congestive heart failure - associated structural remodeling induced by ventricular tachypacing ( 240 bpm for 2 weeks). PUFA pretreatment did not directly change atrial effective refractory period (128 +/- 6 [mean +/- SEM] versus 127 +/- 2 ms; all effective refractory periods at 300-ms cycle lengths) or burst pacing - induced AF duration (5 +/- 4 versus 34 +/- 18 seconds). Atrial tachypacing dogs had shorter refractory periods (73 +/- 6 ms) and greater AF duration (1185 +/- 300 seconds) than shams (119 +/- 5 ms and 20 +/- 11 seconds; P < 0.01 for each). PUFAs did not significantly alter atrial tachypacing effects on refractory periods (77 +/- 8 ms) or AF duration (1128 +/- 412 seconds). PUFAs suppressed ventricular tachypacing - induced increases in AF duration (952 +/- 221 versus 318 +/- 249 seconds; P < 0.05) and attenuated congestive heart failure - related atrial fibrosis (from 19.2 +/- 1.1% to 5.8 +/- 1.0%; P < 0.001) and conduction abnormalities. PUFAs also attenuated ventricular tachypacing - induced hemodynamic dysfunction (eg, left ventricular end-diastolic and left atrial pressure from 12.2 +/- 0.5 and 11.4 +/- 0.6 mm Hg, respectively, to 6.4 +/- 0.5 and 7.0 +/- 0.8 mm Hg; P < 0.01) and phosphorylation of mitogen-activated protein kinases (extracellular-signal related and P38 kinase).Conclusions - PUFAs suppress congestive heart failure - induced atrial structural remodeling and AF promotion but do not affect atrial tachycardia - induced electrical remodeling. The beneficial effects of PUFAs on structural remodeling, possibly related to prevention of mitogen-activated protein kinase activation, may contribute to their clinical anti-AF potential.