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Lu X, Wu T, Huang P, Lin S, Qiu F, Meng XB, Gao J, Li JA: Effect and mechanism of intermittent myocardial ischemia induced by exercise on coronary collateral formation. Am J Phys Med Rehabil 2008;87:803–814.To hypothesize that appropriate intermittent myocardial ischemia induced by exercise could safely promote coronary collateral formation in the ischemic area through the increased expression of vascular endothelial growth factor (VEGF) and its receptor fetal liver kinase-1 (Flk-1).A balloon constrictor was surgically implanted in the first obtuse marginal coronary artery (OM1) of Guangxi BA-MA miniature pigs. The subjects were divided into three groups: sham-operated (SO), pure ischemia (PI), and exercise training (ET). Subjects in the ET group performed individualized treadmill programs with two episodes of exercise-induced ischemia for 8 wks; two preexercise episodes of pure ischemia induced by brief OM1 occlusion were also conducted. Only pure ischemia was induced in the PI group, and the SO group remained sedentary for the experimental period. VEGF and Flk-1 expression levels were measured by Western blot and real-time reverse transcription polymerase chain reaction analyses; capillary density by immunohistochemistry; relative myocardial blood flow by microspheres; and cardiac troponin I by enzyme-linked immunosorbent assay.The relative myocardial blood flow, VEGF, Flk-1, and capillary density in the ET group were statistically higher than those in the PI and SO groups. All parameters in the PI group were statistically higher than those in the SO group. There was no myocardial damage in the ET or PI groups by cardiac troponin I.Intermittent myocardial ischemia induced by exercise with optimal stimulation safely promotes coronary collateral formation through increased VEGF and Flk-1 expression in a porcine model.