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The Additive Effects of Ischemic Postconditioning and Cyclosporine-A on Nitric Oxide Activity and Functions of Diabetic Myocardium Injured by Ischemia/Reperfusion.
MedLine Citation:
PMID:  21828282     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: The interaction of diabetes with cardioprotection by postconditioning in ischemia/reperfusion injury remains unclear. The aim of this study was to investigate the concomitant effects of ischemic postconditioning (IPostC) and cyclosporine-A (CsA) on nitric oxide (NO) content and parameters of cardiac function of the diabetic myocardium injured by ischemia/reperfusion. METHODS: Diabetes was induced by single injection of streptozotocin (50 mg/kg; intraperitoneally [ip]) in Wistar rats (250-320 g) and the diabetic period was 8 weeks. The hearts (n = 96) were removed quickly, mounted on Langendorff apparatus, and then subjected to 30-minute regional ischemia followed by 45-minute reperfusion. Ischemic postconditioning was induced by 3 cycles of 30-second reperfusion/ischemia at the onset of reperfusion. Myocardial function was measured throughout the experiment, and infarct size (IS) was identified by triphenyltetrazolium chloride (TTC) staining. Total amounts of NO metabolites were determined using Griess method and enzyme-linked immunosorbent assay (ELISA) reader. RESULTS: Administration of either IPostC or CsA alone in nondiabetic animals significantly improved myocardial function and reduced the ISs (28% ± 1.9% or 23% ± 2.0% vs 41% ± 2.9% of the risk zone [RZ], respectively; P < .01), but they had no effect on diabetic hearts (35% ± 1.8% or 32% ± 2.1% vs 39% ± 3.1%, respectively). In addition, myocardial NO level was significantly increased by IPostC only in nondiabetic animals (P < .01). However, after administration of CsA (5 minutes before and 10 minutes after the onset of reperfusion) in postconditioned animals, the cardioprotective and NO-enhancing effects of IPostC were restored in diabetic rats (IS: 21% ± 1.1% vs 39% ± 3.1%), similar to those in nondiabetic controls (19% ± 1.3% vs 41% ± 2.9%; P < .01). CONCLUSION: The present study indicated that IPostC or CsA failed to affect NO levels and failed to protect the diabetic myocardium against ischemia/reperfusion injury. Moreover, concomitant administration of CsA and IPostC at reperfusion can increase NO content and protect the diabetic myocardium.
Authors:
Reza Badalzadeh; Mustafa Mohammadi; Moslem Najafi; Naser Ahmadiasl; Safar Farajnia; Hadi Ebrahimi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-9
Journal Detail:
Title:  Journal of cardiovascular pharmacology and therapeutics     Volume:  -     ISSN:  1940-4034     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9602617     Medline TA:  J Cardiovasc Pharmacol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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