| Objectives:To investigate the effects of PIT and the important role of EPCs on PIT induced remote ischemic myocardium protection in the established rabbit model of controllable myocardial ischemia.Methods:Forty-two rabbits were randomized into six groups:sham-operated (SO), training only (TO), myocardial ischemia (MI), physiological ischemic training (PIT), EPC promotor (PIT+), and EPC inhibitor (PIT-) group. Ischemia was maintained for2min, after which the water was drained from the balloon. This procedure was started a week after the implantation of the balloon and for the next four weeks it was repeated twice a day and five days per week. A blood pressure cuff was placed around both hind limbs of the rabbits. The cuff was inflated to200mmHg until the femoral artery pulse disappeared for3min, followed by a5min deflation. PIT started after the first induction of myocardial ischemia in the respective experimental groups and was repeated three times a day, five days per week, over4weeks. At the endpoint, VEGF protein and EPCs were measured in plasma and myocardium. Coronary blood flow (CBF) and coronary collateral blood flow (CCBF) were also determined. Groups were compared using non-parametric statistics and associations between agents explored with fractional polynomials regression.Results:VEGF protein levels were highest in PIT+and PIT. PIT did differ significantly from SO, TO, MI, and PIT-regarding plasma VEGF protein levels as well as protein levels in myocardium. EPCs were highest in PIT+followed by PIT. PIT did differ significantly from SO, TO, MI, and PIT-regarding plasma EPCs. CCBF and CCBF/CBF were significantly increased in PIT+and PIT as compared to controls. VEGF explained up to43%of variance in EPCs. EPCs explained up to90%of variance in CCBF and CCBF/CBF.Conclusion:PIT improves revascularization via VEGF-mediated mobilization of EPCs and may be a new approach in the treatment of patients with CHD. |
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