In the present study, we hypothesized that postcon (postconditioning) confers cardioprotection in vivo by reducing the production of ONOO− (peroxynitrite) and nitro-oxidative stress subsequent to the inhibition of the iNOS (inducible NO synthase). Patients with AMI (acute myocardial infarct) were randomly assigned to undergo percutaneous coronary intervention without (control) or with ischaemic postcon by three episodes of 30-s inflation and 30-s deflation of the angioplasty balloon. Animal models of MI/R (myocardial ischaemia/reperfusion) injury were induced in rats by occluding the left coronary artery for 40 min followed by 4-h reperfusion. Rats were randomized to receive vehicle, postcon (three cycles of 10-s reperfusion and 10-s coronary re-occlusion preceding full reperfusion), the selective iNOS inhibitor 1400W or postcon plus 3-morpholinosydnonimine (an ONOO− donor). Postcon in patients reduced iNOS activity in white blood cells, decreased plasma nitrotyrosine, a fingerprint of ONOO− and an index of nitro-oxidative stress, and improved cardiac function (P<0.01 compared with control). In rats, postcon reduced post-ischaemic myocardial iNOS activity and nitrotyrosine formation, reduced myocardial infarct size (all P<0.05 compared with control) and improved cardiac function. Administration of 1400W resembled, whereas 3-morpholinosydnonimine abolished, the effects of postcon. In conclusion, reduction in ONOO−-induced nitro-oxidative stress subsequent to the inhibition of iNOS represents a major mechanism whereby postcon confers cardioprotection in vivo.
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Research Article|
December 03 2010
Postconditioning attenuates myocardial injury by reducing nitro-oxidative stress in vivo in rats and in humans
Qian Fan;
Qian Fan
*Heart Center, Beijing Chaoyang Hospital-Affiliate of Beijing Capital Medical University, 8 Gongtinan Road, Beijing 100020, People's Republic of China
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Xin-Chun Yang;
*Heart Center, Beijing Chaoyang Hospital-Affiliate of Beijing Capital Medical University, 8 Gongtinan Road, Beijing 100020, People's Republic of China
Correspondence: Dr Xin-Chun Yang (email yangxc@medmail.com.cn) or Dr Zhengyuan Xia (email zyxia@hku.hk).
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Yu Liu;
Yu Liu
*Heart Center, Beijing Chaoyang Hospital-Affiliate of Beijing Capital Medical University, 8 Gongtinan Road, Beijing 100020, People's Republic of China
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Le-Feng Wang;
Le-Feng Wang
*Heart Center, Beijing Chaoyang Hospital-Affiliate of Beijing Capital Medical University, 8 Gongtinan Road, Beijing 100020, People's Republic of China
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Sheng-Hui Liu;
Sheng-Hui Liu
*Heart Center, Beijing Chaoyang Hospital-Affiliate of Beijing Capital Medical University, 8 Gongtinan Road, Beijing 100020, People's Republic of China
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Yong-Gui Ge;
Yong-Gui Ge
*Heart Center, Beijing Chaoyang Hospital-Affiliate of Beijing Capital Medical University, 8 Gongtinan Road, Beijing 100020, People's Republic of China
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Mu-Lie Chen;
Mu-Lie Chen
*Heart Center, Beijing Chaoyang Hospital-Affiliate of Beijing Capital Medical University, 8 Gongtinan Road, Beijing 100020, People's Republic of China
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Wen Wang;
Wen Wang
†Department of Pathophysiology, Beijing Capital Medical University, 10 Youanwenwai Road, Beijing 100069, People's Republic of China
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Li-Ke Zhang;
Li-Ke Zhang
†Department of Pathophysiology, Beijing Capital Medical University, 10 Youanwenwai Road, Beijing 100069, People's Republic of China
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Michael G. Irwin;
Michael G. Irwin
‡Research Centre of Heart, Brain, Hormone and Healthy Aging and Department of Anesthesiology, University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, People's Republic of China
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Zhengyuan Xia
‡Research Centre of Heart, Brain, Hormone and Healthy Aging and Department of Anesthesiology, University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, People's Republic of China
Correspondence: Dr Xin-Chun Yang (email yangxc@medmail.com.cn) or Dr Zhengyuan Xia (email zyxia@hku.hk).
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Publisher: Portland Press Ltd
Received:
July 14 2010
Revision Received:
September 09 2010
Accepted:
October 05 2010
Accepted Manuscript online:
October 05 2010
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2011 Biochemical Society
2011
Clin Sci (Lond) (2011) 120 (6): 251–261.
Article history
Received:
July 14 2010
Revision Received:
September 09 2010
Accepted:
October 05 2010
Accepted Manuscript online:
October 05 2010
Citation
Qian Fan, Xin-Chun Yang, Yu Liu, Le-Feng Wang, Sheng-Hui Liu, Yong-Gui Ge, Mu-Lie Chen, Wen Wang, Li-Ke Zhang, Michael G. Irwin, Zhengyuan Xia; Postconditioning attenuates myocardial injury by reducing nitro-oxidative stress in vivo in rats and in humans. Clin Sci (Lond) 1 March 2011; 120 (6): 251–261. doi: https://doi.org/10.1042/CS20100369
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