Protection of Human Myocardium by Bone Marrow Cells: Role of Long-Term Administration of the Mitochondrial KATP Channel Opener Nicorandil

BackgroundWe 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 mitoKATP 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.Materials and MethodsBMCs 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).ResultsCreatine 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.ConclusionsThe cardioprotective properties of BMCs from subjects treated with the mitoKATP channel opener nicorandil are preserved; however, the myocardium of these patients cannot benefit from the cardioprotective effect of BMCs due to an unresponsive myocardium.