ABSTRACT
Objective To explore the effects of vascular endothelial growth factor (VEGF) and nitric oxide (NO) on coronary collateral blood flow (CCBF) in a rabbit model of physical ischemic training (PIT),and to provide a foundation for the study of the mechanism of collateral circulation formation in PIT.Methods Models of intermittent myocardial ischemia were established in 55 rabbits by installing a water balloon constrictor on the left ventricular coronary artery.The rabbits were then divided into a sham-operation group,a pure ischemia group,a PIT group,a PIT group with NO inhibition pretreatment,a PIT group with VEGF inhibition treatment,and a PIT group with both NO and VEGF inhibition pretreatment.Microspheres were injected at modeling and before sacrifice before and after ischemic stimulation.At the termination of the experiment the ischemic myocardial tissue of the left ventricular anterior wall was sampled,and then relative CCBF was measured using the microspheres.Results There was no significant difference among the 6 groups before training.After training prominent differences among the groups were observed,with the PIT group having the greatest increase in CCBF.CCBF in the pure ischemia group,the PIT group,and the PIT group with NO inhibition pretreatment were significantly higher than in the sham-operation group.Significant differences were also found between the PIT group and the three pretreatment groups.CCBF in the PIT group with NO pretreatment and VEGF inhibition was significantly different from that in the NO pretreatment group,while it was not found in the group with VEGF inhibition pretreatment.The CCBF in the group with VEGF inhibition pretreatment and the group with NO inhibition pretreatment was similar.Conclusions PIT can improve CCBF to the remote ischemic myocardium when combined with VEGF and NO pretreatment.Blocking VEGF or NO can reduce CCBF after training,and both VEGF and NO are involved in the formation of collateral circulation,with VEGF playing the major role.