The Effect Of Vascular Endothelial Growth Factor-Nitric Oxide On Coronary Collateral Blood Flow In Physical Ischemic Training Of Rabbit

Objective：Physiological ischemic training (PIT) of normal skeletal musclecontribute to myocardial angiogenesis. The aim of the study was to explore the effectof vascular endothelial growth factor（VEGF） and nitric oxide（NO） on coronarycollateral blood flow (CCBF) in rabbit PIT model, and provide foundation for thestudy of the mechanism of collateral circulation formation in PIT.Methods： Intermittent myocardial ischemic models were established byinstalling a water balloon constrictor on the left ventricular coronary artery with55rabbits, which were divided into6groups, namely the sham-operation group, the pureischemia group, the PIT group, the PIT group with pretreatment of NO inhibition, thePIT group with pretreatment of VEGF inhibition, the PIT group with pretreatment ofNO and VEGF inhibition. Colored microsphere was used to record the CCBF. Yellowmicrosphere was injected after install the water balloon constrictor at modeling torecord the blood flow of myocardium without ischemic, and eosin microsphere wasinjected after2min’s ischemic stimulation to record the CCBF after the opening ofthe collateral circulation. Likewise, before the sacrifice white microsphere wasinjected before ischemic stimulation to record the blood flow after training, and afterischemic stimulation violet microsphere was injected to record the CCBF after theopening of the collateral circulation. At the termination of the experiment, theischemic myocardial tissue of left ventricular anterior wall was taken, and then relative CCBF was measured by microsphere.Results：1. No significant differences were found before training among the sixgroups, and after training prominent differences were found among groups with thePIT group having the highest increase of CCBF.2. The pure ischemia group, the PITgroup, and the PIT group with pretreatment of NO inhibition were significantlyhigher than the sham-operation group (P＜0.05).3. Significant differences were alsofound between PIT group and the other three pretreatment PIT groups(P＜0.05).4.CCBF in the PIT group with pretreatment of NO and VEGF inhibition was differentwith the PIT with pretreatment of NO group, which was not found with the group ofPIT with pretreatment of VEGF inhibition.5. The CCBF was similar between the PITgroup with pretreatment of VEGF inhibition and the group of NO inhibitionpretreatment.Conclusions： PIT can improve CCBF of remote ischemic myocardium byVEGF and NO. Blocking VEGF or NO can reduce CCBF after training, and bothVEGF and NO are involved in the formation of collateral circulation，with VEGF playing the major role.