Effects Of The Applied External Weak Steady Direct Current Electrical Fields On Diastolic Function After Balloon Injury In The Rabbit Abdominal Aorta

1,Background and ObjectiveThe role of percutaneous coronary intervention (PCI) in the treatment of coronary artery disease has grown at an astronomical pace. However, restenosis after PCI has always been an important issue and hampered the further development of PCI Seriously. Some related researchs indicate that there is a significant correlation between the incidence of restenosis after PCI and the endothelial dysfunction caused by PCI. PCI will inevitably lead to vascular endothelial injury and cause endothelial dysfunction, Which will lead to transitional proliferation of new endothelial in the local of vascular endothelial injury, and then cause the restenosis. Therefore, improving the endothelial function after PCI can play an important role in precenting RS. Although the means for improving the endothelial function after PCI in currently have recovered the endothelial function and played a useful role to RS in some extent, the preblom of RS after PCI is still not completely solved. Therefore, one of the hot problems in interventional therapy is to find a better way to promote the recovery endothelial function after vascular endothelial injuryThere are the endogenous electrical fields in the process of embryonic development and wound healing, which have the promoting contribution to tissue development and wound healing. Some researches indicated that external electric field induce directional migration and proliferation of a variety of different cells. Vasculay endothelial cells migrate toward the cathode of an applied external electric field. It shows that external electric field have effect on biological behaverior of endothelial cells. Therefore, it is worthy of investigating whether the repair process of endothelial diastolic function after arterial injury could be influenced by the applied steady direct current electrical fields.The effects and mechanism of the applied weak steady direct current electrical fields on ischemia/infarct myocardium and vascular neointimal hyperplasia and re-endothelialization after balloon injury were preliminarily studied by our research group, and the power device and electrode used for applying the electrical fields to experimental animals was designed. Based on the researches mentioned above, we builded the balloon injury model of rabbit abdominal aorta and applied electrical fields so that we could observe the effect about the repair process of endothelial diastolic function after arterial injury caused by electrical fields. In addition, we investigated its possible mechanisms from NOS-NO signaling pathway.2. MethodsIn the first part, A rabbit model of abdominal aorta balloon injury is established and we observe the process of vascular neointimal hyperplasia.(1) The Percutaneous transluminal coronary angioplasty(PTCA) balloon catheter is inserted in the lower abdominal aorta though the right femoral artery after cutting down the rabbits skin about the right femoral arrery. Then,we expand the balloon and push and pull the balloon catheter repeatedly so as to injury the abdominal aorta neointimal. Though the above methods ,we establish the rabbit model of abdominal aorta balloon injury.(2) The rabbits are sacrificed at different time points after building the model of abdominal aorta balloon injury successfully and we observe the process of vascular neointimal hyperplasia though evans blue staining.In the second part, we established the balloon injury model of rabbit abdominal aorta and implanted stimulating electrode in the psoas major muscle of two sides of rabbit abdominal aorta. We divided 40 healthy Japanese white rabbits into electrical fields group, control group, electrical field+ L-NAME group and electrical field+ L-Arg group randomly. The rabbits of electrical fields group were given 4.0v current electric stimulation 30 minutes once a day after balloon injury. But the rabbits of control group were not given electric stimulation. The rabbits of both electrical fields group and control group were sacrificed on 1^st, 2^nd and 4^th week after balloon injury.The rabbits of electrical field+L-NAME group were given 4.0v current electric stimulation 30 minutes once a day and given L-NAME(50mg/kg) though intraperitoneal injection after balloon injury ; The rabbits of electrical field + L-Arg group were were given 4.0v current electric stimulation 30 minutes once a day and given L-Arg(100mg/kg) though gastric tube after balloon injury. The rabbits of both electrical field+L-NAME group and electrical field + L-Arg group were sacrificed on 4^th week after balloon injury. Vascular endothelial function was observed and the concentration of NO ,NOS and VEGF was examined though ELLISA.3. Results(1) We established the rabbit model of abdominal aorta balloon injury successfully and observe the process of vascular endothelial repair about this model and provide a basis platform for electrical fields intervening the experiment.(2) After establishing the balloon injury model of rabbit abdominal aorta, the result of Evans blue staining indicated that the process of neointimal hyperplasia was basic completed at 4^th week after balloon injury and the area ratio between the neointimal hyperplasia and the total vascular endothelial injured area is 96.57%±1.20%.(3) The vascular maximum degree of relaxation of the rabbits in electrical field group were greater compared with which of the rabbits in control group and electrical field+L-NAME group (P<0.05) and lower compared with which of the rabbits in electrical field+L-Arg group (P<0.05) at 4^th week after balloon injury.(4) The concentration of NO (613.33±2.57 umol/L,652.18±2.66 umol/L) , the concentration of NOS (1997.43±9.58 umol/L,2116.89±9.05 umol/L) and the concentration of VEGF (258.63±1.99 ng/L,272.09±1.30 ng/L) of the rabbits vascular tissue in electrical field group were greater compared with which of the rabbits vascular tissue in control group at 2^nd and 4^th week after balloon injury. The concentration of NO of the rabbits vascular tissue in electrical field group were greater compared with which of the rabbits in electrical field+L-NAME group (P<0.05) and lower compared with which of the rabbits vascular tissue in electrical field+L-Arg group (P<0.05) .4. Conclusions(1) Establishment model of vascular endothelial injury used rabbits abdominal aorta is effective, convenient and practical. This model can be successfully applied to the experiment about the effect of external steady direct current electrical fields on vascular endothelial diastolic function.(2) It indicated that the external steady direct current electrical field is favorable for the recovery of endothelial functions.(3) It indicated that the external steady direct current electrical field can promote the increment of the plasm level of NO,NOS and VEGF secreted by vascular endothelium cell. (4) The role that the external steady direct current electrical field improve vascular endothelial function may be come true though promoting the increment of the level of VEGF secreted by vascular endothelium cell, and then though the NOS-NO signaling pathway.