title: The infarct size-limiting effect of ischemic postconditioning (IPOC) is suppressed in isolated hyperhomocysteinemic (Hhcy) rat hearts: the reasonable role of PKC-delta.
abstract: BACKGROUND
  Recently we have demonstrated that the cardioprotective potential of ischemic postconditioning (IPOC) against ischemia and reperfusion (I/R)-induced myocardial injury was markedly suppressed in hyperhomocysteinemic (Hhcy) rat hearts. The present study investigated the possible role of PKC-delta in Hhcy-induced suppression of myocardial infarct size-limiting effect of IPOC.
  
  
  METHODS
  Isolated Langendorff's perfused normal and Hhcy rat hearts were subjected to 30-min global ischemia (I), followed by 120-min reperfusion (R). The myocardial damage was assessed by measuring the infarct size, and analyzing the release of LDH and CK-MB in coronary effluent. The oxidative stress in the heart was assessed by measuring lipid peroxidation and superoxide anion generation.
  
  
  RESULTS
  The I/R produced myocardial injury in normal and Hhcy rat hearts by increasing myocardial infarct size, LDH and CK in coronary effluent and oxidative stress. Hhcy rat hearts exhibited enhanced I/R-induced myocardial injury and high oxidative stress as compared to normal rat hearts subjected to I/R. The IPOC (six brief episodes of I/R, 10s each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts; but IPOC-mediated cardioprotection was abolished in Hhcy rat hearts. Treatment with rottlerin (10 microM), a selective inhibitor of PKC-delta, did not affect the cardioprotective effect of IPOC in normal rat hearts; but its treatment significantly restored the myocardial infarct size-limiting effect of IPOC in Hhcy rat hearts.
  
  
  CONCLUSIONS
  The high oxidative stress produced in Hhcy rat hearts during reperfusion may activate PKC-delta, which may be responsible for impairing the infarct size-limiting potential of IPOC in Hhcy rat hearts.
authors.affiliation: Cardiovascular Pharmacology Division, ISF College of Pharmacy, Moga 142 001, Punjab, India.
authors.forename: Ankur
authors.initials: A
authors.lastname: Rohilla
authors.forename: Pitchai
authors.initials: P
authors.lastname: Balakumar
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D005260:Female; D020138:Hyperhomocysteinemia / Q000150:complications; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D018384:Oxidative Stress; D051745:Protein Kinase C-delta / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D013481:Superoxides; C085746:rottlerin; D007770:L-Lactate Dehydrogenase; D051745:Protein Kinase C-delta; D052279:Creatine Kinase, MB Form