Dynamics of endogenous endothelial progenitor cells homing modulated by physiological ischaemia training

OBJECTIVE: To locate and trace endogenous endothelial progenitor cells (EPCs) in rabbits subjected to myocardial ischaemia and/or physiological ischaemia training. METHODS: Rabbits were randomly divided into 4 groups: a myocardial ischaemia group (subjected to myocardial ischaemia only); a physiological ischaemia training group (subjected to physiological ischaemia training only); a physiological ischaemia training-myocardial ischaemia group (subjected to both myocardial ischaemia and physiological ischaemia training); and a sham-operated group. Myocardial ischaemia was induced experimentally by a 2-min ischaemia, followed by a 1-h reperfusion. Physiological ischaemia training involved a 4-min isometric contraction elicited by electrical stimulation (biphase square wave, 40 Hz, 1 ms), which generated a contraction force at 40% of the maximal isometric contraction force. Myocardial ischaemia I and/or physiological ischaemia training were performed twice a day, 5 days a week for 4 weeks. Capillary densities and EPC levels in both blood and the ischaemic heart region were then measured. EPCs were traced by double-labelling with super paramagnetic iron oxide and chloromethyl-benzamidodialkylcarbocyanine. RESULTS: EPC levels in the blood and the ischaemic heart region both improved significantly in the physiological ischaemia training-myocardial ischaemia group (mean 0.046% (standard deviation (SD) 0.007), 0.013% (SD 0.005)) and group myocardial ischaemia (mean 0.038% (SD 0.016), 0.008% (SD 0.004)). For the physiological ischaemia training group, moderately raised EPCs were found in the blood (0.026 ± 0.010%), but not in the heart. Capillary density increased in the physiological ischaemia training-myocardial ischaemia and myocardial ischaemia groups. The dual-labelled EPCs were confirmed in the ischaemic heart region. Pearson's analysis demonstrated that there is a positive correlation between EPC levels in the blood and the heart region (p < 0.05), and between circulating EPCs and the capillary (p < 0.05) for the physiological ischaemia training-myocardial ischaemia group. CONCLUSION: Physiological ischaemia training can effectively improve endogenous EPCs. Their homing process from the circulating blood to the ischaemic myocardium was clearly traced in this study on rabbits. This homing process is of great importance for remote neovascularization.