TY - JOUR
T1 - Eicosapentaenoic acid reduces ischemic ventricular fibrillation via altering monophasic action potential in pigs
AU - Tsuburaya, Ryuji
AU - Yasuda, Satoshi
AU - Ito, Yoshitaka
AU - Shiroto, Takashi
AU - Gao, Jun Yi
AU - Ito, Kenta
AU - Shimokawa, Hiroaki
N1 - Funding Information:
The authors' work was supported in part by the grants-in-aid [ 18890018 ] from the Scientific Research ; and the global COE project [ F02 ] from the Japanese Ministry of Education, Culture, Sports, Science, and Technology, Tokyo, Japan . The authors thank Dr. Teruyuki Yanagisawa (Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine), Dr. Masaaki Soma (Mochida Pharmaceutical Co., Ltd.) and Dr. Takatoshi Hizume (Kyushu University Graduate School of Medicine) for their valuable cooperation in the present study and Mochida Pharmaceutical Co., Ltd. for providing the EPA.
PY - 2011/9
Y1 - 2011/9
N2 - Although high intake of n-3 fatty acids is associated with reduced mortality of patients with ischemic heart disease, especially reduction in sudden cardiac death (SCD), the detailed mechanisms remain to be elucidated. Thus, the present study was designed to examine whether long-term treatment with eicosapentaenoic acid (EPA), a major component of n-3 fatty acids, reduces ischemia-induced ventricular fibrillation (VF) in pigs in vivo, and if so, what molecular mechanisms are involved. Male pigs were treated with either a control chow (control group) or a control chow plus EPA (600mg/kg/day, PO, EPA group) for 3weeks and were subjected to myocardial ischemia for 90min (n=8 each) with measurement of the monophasic action potential (MAP), as a marker of ventricular electrophysiological activities. The EPA treatment significantly attenuated the occurrence of VF (control 5.1±1.7 vs. EPA 1.5±0.8 times/animal, P<0.05) and markedly reduced the mortality (control 50% vs. EPA 0%, P<0.05), with the attenuation of MAP duration shortening during ischemia (control -28.1±3.0% vs. EPA -18.2±1.4%, P<0.05). These beneficial effects of EPA were abolished by pre-treatment with cromakalim, a K ATP channel opener (0.3μg/kg/min, IC). Furthermore, EPA significantly inhibited the mRNA and protein expression of Kir6.2, a major component of sarcolemmal K ATP channels, in both the ischemic region and non-ischemic regions. These results indicate that long-term treatment with EPA reduces ischemia-induced VF and SCD in pigs in vivo, for which attenuation of MAP duration shortening may be involved.
AB - Although high intake of n-3 fatty acids is associated with reduced mortality of patients with ischemic heart disease, especially reduction in sudden cardiac death (SCD), the detailed mechanisms remain to be elucidated. Thus, the present study was designed to examine whether long-term treatment with eicosapentaenoic acid (EPA), a major component of n-3 fatty acids, reduces ischemia-induced ventricular fibrillation (VF) in pigs in vivo, and if so, what molecular mechanisms are involved. Male pigs were treated with either a control chow (control group) or a control chow plus EPA (600mg/kg/day, PO, EPA group) for 3weeks and were subjected to myocardial ischemia for 90min (n=8 each) with measurement of the monophasic action potential (MAP), as a marker of ventricular electrophysiological activities. The EPA treatment significantly attenuated the occurrence of VF (control 5.1±1.7 vs. EPA 1.5±0.8 times/animal, P<0.05) and markedly reduced the mortality (control 50% vs. EPA 0%, P<0.05), with the attenuation of MAP duration shortening during ischemia (control -28.1±3.0% vs. EPA -18.2±1.4%, P<0.05). These beneficial effects of EPA were abolished by pre-treatment with cromakalim, a K ATP channel opener (0.3μg/kg/min, IC). Furthermore, EPA significantly inhibited the mRNA and protein expression of Kir6.2, a major component of sarcolemmal K ATP channels, in both the ischemic region and non-ischemic regions. These results indicate that long-term treatment with EPA reduces ischemia-induced VF and SCD in pigs in vivo, for which attenuation of MAP duration shortening may be involved.
KW - Fish oils
KW - Ischemia
KW - K channel
KW - Sudden death
KW - Ventricular arrhythmias
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U2 - 10.1016/j.yjmcc.2011.05.018
DO - 10.1016/j.yjmcc.2011.05.018
M3 - Article
C2 - 21651914
AN - SCOPUS:79960895693
VL - 51
SP - 329
EP - 336
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 3
ER -