title: The additive effects of ischemic postconditioning and cyclosporine-A on nitric oxide activity and functions of diabetic myocardium injured by ischemia/reperfusion.
abstract: 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).
  
  
  CONCLUSIONS
  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.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Badalzadeh
authors.forename: Mustafa
authors.initials: M
authors.lastname: Mohammadi
authors.forename: Moslem
authors.initials: M
authors.lastname: Najafi
authors.forename: Naser
authors.initials: N
authors.lastname: Ahmadiasl
authors.forename: Safar
authors.initials: S
authors.lastname: Farajnia
authors.forename: Hadi
authors.initials: H
authors.lastname: Ebrahimi
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology* / Q000628:therapy; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D009569:Nitric Oxide; D013311:Streptozocin; D016572:Cyclosporine