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Am J Physiol Heart Circ Physiol (April 3, 2003). doi:10.1152/ajpheart.01064.2002
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Submitted on December 9, 2002
Accepted on March 27, 2003

Inhibition of myocardial injury by ischemic post-conditioning during reperfusion: comparison with ischemic preconditioning

Zhi-Qing Zhao1*, Joel S Corvera1, Michael E Halkos1, Faraz Kerendi1, Ning-Ping Wang1, Robert A Guyton1, and Jakob Vinten-Johansen

1 Department of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, GA, USA

* To whom correspondence should be addressed. E-mail: zzhao{at}emory.edu.

Ischemic preconditioning (Pre-con) is an adaptive response triggered by a brief ischemia applied before a prolonged coronary occlusion. We tested the hypothesis that repetitive ischemia applied during early reperfusion (R), i.e. post-conditioning (Post-con), is cardioprotective by attenuating R injury. In anesthetized open-chest dogs, the LAD was occluded for 60 min and reperfused for 3 h. In Controls (Con, n=10), there was no intervention. In Pre-con (n=9), the LAD was occluded for 5 min and reperfused for 10 min before the prolonged occlusion. In Post-con (n=10), at the start of R, 3 cycles of 30 s R and 30 s LAD re-occlusion preceded the 3 h of R. Infarct size was significantly less in the Pre-con (15±2%*) and Post-con (14±2%*) groups compared to Con (25±2%). Tissue edema (% water content) in the area at risk was comparably reduced in Pre-con (78.3±1.2*) and Post-con (79.7±0.6*) vs. Con (81.5±0.4). Neutrophil (PMN) accumulation (myeloperoxidase activity, {Delta}abs/min/g tissue) in the area at risk myocardium was comparably reduced in Post-con (10.8±5.5*) and Pre-con (13.4±3.4*) vs. Con (47.4±15.3). Basal endothelial function measured by PMN adherence to post-ischemic LAD endothelium (PMNs/mm2) was comparably attenuated by Post-con and Pre-con (15±0.6* and 12±0.6*) vs. Con (37±1.5), consistent with reduced expression of P-selectin on coronary vascular endothelium in Post-con and Pre-con. Endothelial function assessed by the maximal vasodilator response of post-ischemic LAD to acetylcholine, was significantly greater in Post-con (104±6%*) and Pre-con (109±5%*) vs. Con (71±8%). Plasma malonaldehyde (µM/ml), a product of lipid peroxidation, was significantly less at 1 h of R in Post-con (2.2±0.2*) vs. Con (3.2±0.3), associated with a decrease in superoxide levels revealed by dihydroethidium staining in the myocardial area at risk. These data suggest that Post-con is as effective as Pre-con in reducing infarct size and preserving endothelial function. Post-con may be clinically applicable in coronary interventions, coronary artery bypass surgery, organ transplantation and peripheral revascularization where reperfusion injury is expressed. * P<0.05 Post-con and Pre-con vs. Con.




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J. Taki, T. Higuchi, A. Kawashima, M. Fukuoka, D. Kayano, J. F. Tait, I. Matsunari, K. Nakajima, S. Kinuya, and H. W. Strauss
Effect of Postconditioning on Myocardial 99mTc-Annexin-V Uptake: Comparison with Ischemic Preconditioning and Caspase Inhibitor Treatment
J. Nucl. Med., August 1, 2007; 48(8): 1301 - 1307.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
S. Y. Lim, S. M. Davidson, D. J. Hausenloy, and D. M. Yellon
Preconditioning and postconditioning: The essential role of the mitochondrial permeability transition pore
Cardiovasc Res, August 1, 2007; 75(3): 530 - 535.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
C. Penna, D. Mancardi, R. Rastaldo, G. Losano, and P. Pagliaro
Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling
Cardiovasc Res, July 1, 2007; 75(1): 168 - 177.
[Abstract] [Full Text] [PDF]

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 J CARDIOVASC PHARMACOL THERHome page
J. Dow and R. A. Kloner
Postconditioning Does Not Reduce Myocardial Infarct Size in an In Vivo Regional Ischemia Rodent Model
Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2007; 12(2): 153 - 163.
[Abstract] [PDF]

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 HeartHome page
D. J Hausenloy and D. M Yellon
The evolving story of "conditioning" to protect against acute myocardial ischaemia-reperfusion injury
Heart, June 1, 2007; 93(6): 649 - 651.
[Abstract] [Full Text] [PDF]

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 J. Thorac. Cardiovasc. Surg.Home page
W. Luo, B. Li, G. Lin, and R. Huang
Postconditioning in cardiac surgery for tetralogy of Fallot
J. Thorac. Cardiovasc. Surg., May 1, 2007; 133(5): 1373 - 1374.
[Full Text] [PDF]

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 J Am Coll CardiolHome page
W. Y. Vanagt, R. N. Cornelussen, T. C. Baynham, A. Van Hunnik, Q. P. Poulina, F. Babiker, J. Spinelli, T. Delhaas, and F. W. Prinzen
Pacing-Induced Dyssynchrony During Early Reperfusion Reduces Infarct Size
J. Am. Coll. Cardiol., May 1, 2007; 49(17): 1813 - 1819.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
S. M. Davidson and M. R. Duchen
Endothelial Mitochondria: Contributing to Vascular Function and Disease
Circ. Res., April 27, 2007; 100(8): 1128 - 1141.
[Abstract] [Full Text] [PDF]

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 J. Thorac. Cardiovasc. Surg.Home page
E. Shi, X. Jiang, T. Kazui, N. Washiyama, K. Yamashita, H. Terada, and A. H. M. Bashar
Controlled low-pressure perfusion at the beginning of reperfusion attenuates neurologic injury after spinal cord ischemia
J. Thorac. Cardiovasc. Surg., April 1, 2007; 133(4): 942 - 948.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
A. Lerman, D. R. Holmes, J. Herrmann, and B. J. Gersh
Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both?
Eur. Heart J., April 1, 2007; 28(7): 788 - 797.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
M. R. Schmidt, M. Smerup, I. E. Konstantinov, M. Shimizu, J. Li, M. Cheung, P. A. White, S. B. Kristiansen, K. Sorensen, V. Dzavik, et al.
Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning
Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1883 - H1890.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Fujita, H. Asanuma, A. Hirata, M. Wakeno, H. Takahama, H. Sasaki, J. Kim, S. Takashima, O. Tsukamoto, T. Minamino, et al.
Prolonged transient acidosis during early reperfusion contributes to the cardioprotective effects of postconditioning
Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H2004 - H2008.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
L. Tao, E. Gao, X. Jiao, Y. Yuan, S. Li, T. A. Christopher, B. L. Lopez, W. Koch, L. Chan, B. J. Goldstein, et al.
Adiponectin Cardioprotection After Myocardial Ischemia/Reperfusion Involves the Reduction of Oxidative/Nitrative Stress
Circulation, March 20, 2007; 115(11): 1408 - 1416.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
O. C. Manintveld, M. te Lintel Hekkert, E. J. van den Bos, G. M. Suurenbroek, D. H. Dekkers, P. D. Verdouw, J. M. Lamers, and D. J. Duncker
Cardiac effects of postconditioning depend critically on the duration of index ischemia
Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1551 - H1560.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
P. Pacher, J. S. Beckman, and L. Liaudet
Nitric Oxide and Peroxynitrite in Health and Disease
Physiol Rev, January 1, 2007; 87(1): 315 - 424.
[Abstract] [Full Text] [PDF]


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