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Diannexin reduces no-reflow after reperfusion in rabbits with large ischemic myocardial risk zones.
MedLine Citation:
PMID:  20946319     Owner:  NLM     Status:  In-Data-Review    
Introduction and Aims: In patients with ST-segment elevation myocardial infarction who receive percutaneous coronary intervention and stenting, a large zone with no-reflow is associated with adverse outcomes. During myocardial ischemia/reperfusion, phosphatidylserine (PS) translocates to the surface of endothelial cells triggering attachment of platelets and leukocytes, thus impairing microvascular blood flow. Diannexin, a recombinant dimer of the endogenous human annexin V protein, binds PS and thus inhibits the adverse effects of PS. It has been shown to attenuate postischemic reperfusion injury in several experimental models. We speculated that Diannexin would reduce no-reflow in the heart after coronary artery occlusion (CAO) and reperfusion. Rabbits received: (1) Diannexin 5 min pre-CAO (diannexin pre ischemia [DPI], 400 μg/kg, n = 17), or (2) Diannexin 5 min pre-coronary reperfusion (diannexin pre reperfusion [DPR], 400 μg/kg, n = 20), or (3) saline (Cont, n = 18), with 30 min CAO and 3 h reperfusion. In a secondary analysis, rabbits were divided into two groups based on the overall average risk zone size of 29% of the left ventricle (LV): small (<29% of LV) and large (>29% of LV). Results: Overall, risk zones and infarct size, and the no-reflow zone were similar in all groups. In hearts with large risk zones the no-reflow area was significantly smaller in both drug-treated groups (DPI, 22 ± 5% and DPR, 22 ± 3% vs. control 40 ± 3%, P < 0.006), the hemorrhagic areas were significantly smaller, and infarct size was reduced at the P < 0.06 level compared with control. In animals with small risk zones there were no significant differences. Diannexin treatment did not affect hemodynamics or LV function. Conclusion: Diannexin was cardioprotective in rabbits with a severe ischemic insult. This is important, because large infarcts accompanied by no-reflow in humans are associated with increased complications. In animals with small risk zones, no significant drug effect was observed.
Sharon L Hale; Anthony C Allison; Robert A Kloner
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Publication Detail:
Type:  Journal Article     Date:  2010-10-14
Journal Detail:
Title:  Cardiovascular therapeutics     Volume:  29     ISSN:  1755-5922     ISO Abbreviation:  Cardiovasc Ther     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101319630     Medline TA:  Cardiovasc Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  e42-52     Citation Subset:  IM    
Copyright Information:
© 2010 Blackwell Publishing Ltd.
The Heart Institute of Good Samaritan Hospital, Los Angeles, CA, USA Alavita Pharmaceuticals, Mountain View, CA, USA The Keck School of Medicine, Division of Cardiovascular Medicine, University of Southern California, Los Angeles, CA, USA.
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