title: Protection of human myocardium by bone marrow cells: role of long-term administration of the mitochondrial K(ATP) channel opener nicorandil.
abstract: BACKGROUND
  We have previously demonstrated that bone marrow cells (BMCs) afford myocardial protection as potent as ischemic preconditioning (IP) and also that the myocardium of patients treated with the mitoK(ATP) channel opener nicorandil cannot be protected by IP. Here, we investigated whether nicorandil influences the cardioprotection elicited by BMCs and whether any loss in protection can be rescued by naïve allogenic BMCs.
  
  
  METHODS
  BMCs and right atrial appendage were obtained from patients on long-term treatment and nontreated with nicorandil. The atrial myocardium was subjected to 90 min ischemia/120 min reoxygenation at 37°C in the presence and absence of autologous and allogenic BMCs. Some muscles were subjected to IP prior to ischemia and served as positive controls. Tissue injury was assessed by creatine kinase released during reoxygenation, and cell necrosis and apoptosis were determined by propidium iodide and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).
  
  
  RESULTS
  Creatine kinase (CK) release and cell necrosis and apoptosis induced by ischemia were not significantly reduced by IP in the myocardium from nicorandil subjects and values were also unaffected by the co-incubation with autologous or allogenic BMCs from subjects not treated with nicorandil (naïve BMCs). However, when the myocardium from subjects not treated with nicorandil was co-incubated with autologous BMCs or with allogenic BMCs from subjects treated with nicorandil, there was a similar significant reduction in CK release, cell necrosis and apoptosis.
  
  
  CONCLUSIONS
  The cardioprotective properties of BMCs from subjects treated with the mitoK(ATP) channel opener nicorandil are preserved; however, the myocardium of these patients cannot benefit from the cardioprotective effect of BMCs due to an unresponsive myocardium.
authors.affiliation: Cardiac Surgery Unit, Department of Cardiovascular Sciences, University of Leicester, United Kingdom.
authors.forename: Vien Khach
authors.initials: VK
authors.lastname: Lai
authors.forename: Manuel
authors.initials: M
authors.lastname: Galiñanes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D020517:Atrial Appendage / Q000187:drug effects* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D009336:Necrosis; D020108:Nicorandil / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D020108:Nicorandil