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Department of Cardiothoracic Surgery, The Carlyle Fraser Heart Center/Crawford Long Hospital, Emory University School of Medicine, Atlanta, Georgia 30308-2225
Submitted 9 December 2002 ; accepted in final form 27 March 2003
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, i.e.,
postconditioning (Post-con), is cardio-protective by attenuating reperfusion
injury. In anesthetized open-chest dogs, the left anterior descending artery
(LAD) was occluded for 60 min and reperfused for 3 h. In controls (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 reperfusion, three cycles of
30-s reperfusion and 30-s LAD reocclusion preceded the 3 h of reperfusion.
Infarct size was significantly less in the Pre-con (15 ± 2%, P
< 0.05) and Post-con (14 ± 2%, P < 0.05) groups compared
with controls (25 ± 3%). Tissue edema (% water content) in the area at
risk was comparably reduced in Pre-con (78.3 ± 1.2, P <
0.05) and Post-con (79.7 ± 0.6, P < 0.05) versus controls
(81.5 ± 0.4). Polymorphonuclear neutrophil (PMN) accumulation
(myeloperoxidase activity,
absorbance·min–1·g
tissue–1) in the area at risk myocardium was
comparably reduced in Post-con (10.8 ± 5.5, P < 0.05) and
Pre-con (13.4 ± 3.4, P < 0.05) versus controls (47.4
± 15.3). Basal endothelial function measured by PMN adherence to
postischemic LAD endothelium (PMNs/mm2) was comparably attenuated
by Post-con and Pre-con (15 ± 0.6 and 12 ± 0.6, P <
0.05) versus controls (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
postischemic LAD to acetylcholine was significantly greater in Post-con (104
± 6%, P < 0.05) and Pre-con (109 ± 5%, P
< 0.05) versus controls (71 ± 8%). Plasma malondialdehyde
(µM/ml), a product of lipid peroxidation, was significantly less at 1 h of
reperfusion in Post-con (2.2 ± 0.2, P < 0.05) versus
controls (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.
infarct size; neutrophils
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 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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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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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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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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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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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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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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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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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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