Ischaemia and reperfusion contribute to the genesis of AF (atrial fibrillation). PVs (pulmonary veins) and the atria are important foci for AF initiation and maintenance. However, the effect of ischaemia and reperfusion on PVs and the atria has not yet been fully elucidated. In the present study, conventional microelectrodes were used to record the APs (action potentials) in isolated rabbit PV, LA (left atrium) and RA (right atrium) specimens during hypoxia and reoxygenation, and pharmacological interventions. Hypoxia reduced the PV beating rates from 1.8±0.1 to 1.3±0.2 and 0.8±0.1 Hz at 30 and 60 min respectively (n=8, P<0.005), and induced EAD (early after depolarization) in three (37.5%) of the PVs and DAD (delayed after depolarization) in one (12.5%) of the PVs. Reoxygenation increased the PV spontaneous rate to 1.4±0.2 Hz (P<0.05) and induced PV burst firings (3.5±0.1 Hz, P<0.001) in six (75%) of the PVs. Hypoxia shortened the AP duration in the LA and PVs, but not in the RA. Pretreatment with glibenclamide attenuated hypoxia-induced decreases in the PV spontaneous activity and the shortening of the LA and PV AP duration. Similar to those in hypoxia, the KATP (ATP-sensitive potassium) channel opener pinacidil (30 μM) decreased PV spontaneous activity and shortened the AP duration. Pretreatment with 5 mM N-MPG [N-(mercaptopropionyl)glycine; a hydroxyl (•OH) free-radical scavenger] or 300 μM chloramphenicol [a cytochrome P450 inhibitor that reduces ROS (reactive oxygen species)] attenuated the rate changes induced by hypoxia and reoxygenation, and also decreased the burst firing incidence. In conclusion, hypoxia and reoxygenation significantly increased PV arrhythmogenesis and induced different electrophysiological responses in the RA and LA, which may play a role in the pathophysiology of AF.
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Research Article|
October 11 2011
Hypoxia and reoxygenation modulate the arrhythmogenic activity of the pulmonary vein and atrium
Yung-Kuo Lin;
Yung-Kuo Lin
*Division of Cardiovascular Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan, Republic of China
†Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China
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Mei-Shou Lai;
Mei-Shou Lai
‡Institute of Physiology, National Defense Medical Center, Taipei, Taiwan, Republic of China
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Yao-Chang Chen;
§Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan, Republic of China
Correspondence: Professor Yi-Jen Chen (email [email protected]) or Dr Yao-Chang Chen (email [email protected]).
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Chen-Chuan Cheng;
Chen-Chuan Cheng
‖Division of Cardiology, Chi-Mei Medical Center, Tainan, Taiwan, Republic of China
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Jen-Hung Huang;
Jen-Hung Huang
*Division of Cardiovascular Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan, Republic of China
†Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China
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Shih-Ann Chen;
Shih-Ann Chen
¶School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
**Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan, Republic of China
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Yi-Jen Chen;
*Division of Cardiovascular Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan, Republic of China
†Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China
Correspondence: Professor Yi-Jen Chen (email [email protected]) or Dr Yao-Chang Chen (email [email protected]).
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Cheng-I Lin
Cheng-I Lin
‡Institute of Physiology, National Defense Medical Center, Taipei, Taiwan, Republic of China
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Publisher: Portland Press Ltd
Received:
April 07 2011
Revision Received:
June 15 2011
Accepted:
August 31 2011
Accepted Manuscript online:
August 31 2011
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2012 Biochemical Society
2012
Clin Sci (Lond) (2012) 122 (3): 121–132.
Article history
Received:
April 07 2011
Revision Received:
June 15 2011
Accepted:
August 31 2011
Accepted Manuscript online:
August 31 2011
Citation
Yung-Kuo Lin, Mei-Shou Lai, Yao-Chang Chen, Chen-Chuan Cheng, Jen-Hung Huang, Shih-Ann Chen, Yi-Jen Chen, Cheng-I Lin; Hypoxia and reoxygenation modulate the arrhythmogenic activity of the pulmonary vein and atrium. Clin Sci (Lond) 1 February 2012; 122 (3): 121–132. doi: https://doi.org/10.1042/CS20110178
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