Effect And Mechanism Of Intermittent Myocardial Ischemia Induced By Exercise On Coronary Collateral Formation

Objective: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).Design: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 3 groups:sham-operated(SO),pure ischemia (PI),and exercise training(ET).Subjects in the ET group performed individualized treadmill programs with 2 episodes of exercise-induced ischemia for 8 weeks;2 pre-exercise 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 RT-PCR analyses;capillary density by immunohistochemistry;relative myocardial blood flow by microspheres; and cardiac troponin I by enzyme-linked immunosorbent assay;Light microscope and electron microscope were also employed to examine whether there was some damage in ischemic area. Results:The capillary density in the ET group was statistically higher than those in the PI(P＜0.01)and SO groups(P＜0.01),the capillary density in the PI group was significantly higher than that in the SO group (P＜0.01).The relative myocardial blood flow in the ET group was higher than those in the PI(P＜0.01)and SO groups(P＜0.01),and this parameter in the PI group was also significantly higher than that in the SO group (P＜0.01).The VEGF protein expression in the ET group were statistically higher than those in the PI(P＜0.05)and SO groups(P＜0.01),The Flk-1 protein expression in the ET group were statistically higher than those in the PI(P＜0.05)and SO groups(P＜0.01);the VEGF(P＜0.05),Flk-1 (P＜0.05)protein expression increased significantly in the PI group compared to that in the SO group.The results of mRNA expression were just the same as the results of VEGF,Flk-1 protein expression.There was no myocardial damage in the ET(P＞0.05)or PI group(P＞0.05)by cardiac troponin I,light microscope and electron microscope.Conclusions: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.