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01-01-2010 | Original Contribution

Attenuation of infarction in cynomolgus monkeys: preconditioning and postconditioning

Authors: Xi-Ming Yang, Yanping Liu, Yongge Liu, Narendra Tandon, Junichi Kambayashi, James M. Downey, Michael V. Cohen

Published in: Basic Research in Cardiology | Issue 1/2010

Abstract

Ischemic pre- (IPC) and post- (IPOC) conditioning are very protective in laboratory animals, but it has not been possible to measure their anti-infarct potency in human hearts. Non-human primates are genetically closer to humans than other laboratory animals, but until now there have been no studies of IPC or IPOC in any primate species. Accordingly the left anterior descending coronary artery of cynomolgus monkeys was occluded for 90 min and reperfused for 4 h. In control animals, only 44% of the risk zone infarcted indicating cynomolgus myocardium is much more resistant to infarction than that of rabbits or rats. The regression line for the infarct-risk zone plot was very linear (r = 0.99), and intersected the risk zone axis at 0.82 cm³. Even small changes in infarct size could be detected as a shift in this line. Collateral flow in 12 monkeys was 6.6% of flow to normal myocardium and not a covariate of infarct size. IPC with two cycles of 10-min coronary occlusion/10-min reperfusion reduced infarction to near zero indicating that the innate resistance to infarction was not caused by constitutive preconditioning. Wortmannin, an antagonist of phosphatidylinositol 3-kinase (PI3-K), administered just before release of the 90-min coronary occlusion attenuated IPC’s infarct-sparing effect by ~50% suggesting that PI3-K was involved in preconditioning’s protection. IPOC with six cycles of 30-s reperfusion/30-s coronary reocclusion, a very protective protocol in most species, was much less protective than IPC. We conclude that ischemic preconditioning is extremely protective in cynomolgus hearts despite their sparse collateralization but, surprisingly, the protocol of IPOC used in this study offers less protection.

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Title: Attenuation of infarction in cynomolgus monkeys: preconditioning and postconditioning
Authors: Xi-Ming Yang
Yanping Liu
Yongge Liu
Narendra Tandon
Junichi Kambayashi
James M. Downey
Michael V. Cohen
Publication date: 01-01-2010
Publisher: D. Steinkopff-Verlag
Published in: Basic Research in Cardiology / Issue 1/2010
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-009-0050-2

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Attenuation of infarction in cynomolgus monkeys: preconditioning and postconditioning

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