Effect Of Cervical Sympathetic Blockade On The Formation Of Aortic Dissection Induced By ?-aminopropionitrile In Rats

Part?Construction of ?-aminopropionitrile-induced aortic dissection model and study of the sympathetic nerve activity in ratsBackground: Aortic dissection(AD)represents one of the most common aortic emergencies with high incidence of morbidity and mortality.Clinical studies have shown that the increased excitability of the sympathetic nerve may be involved with the formation of AD.?-aminopropionitrile(BAPN)-treated animals have been extensively used as a model of AD.BAPN can lead to AD formation by preventing the formation of crosslinks in elastin fibers and collagen.BAPN-induced AD is characterized by vascular medial degeneration and fragmentation of elastic fibers,which resemble the aortic changes in AD patients clinically.The sympathetic nerve over-activity may impact on the progression of AD in this animal model.The BAPN administration is currently been world-wide used to establish the AD model of rat,in which the subcutaneous and oral administration of BAPN with different dosage are most common applied different successful rate of model establishment.Object: The study aimed for observing several commonly used methods for BAPN-induced AD model in rats.We will compare their success rate and survival rate,and choose the most appropriate method for this model.Meanwhile,we will observe the effect of BAPN administration on SNA in rats.Materials and methods: Ten adult Sprague–Dawley(SD)rats weighing 300 g were randomly divided into experimental group and control group in the acute experiment.The renal sympathetic nerve activity(RSNA)was measured directly.Rats in the experimental group were treated with BAPN(666mg/kg)and waited for 1 hour before the test.In the chronic experiment,another 35 immature SD rats weighing 50 g were randomly divided into four groups,including 0.1%BAPN oral administration(group I),0.25%BAPN oral administration(group ?),666mg/kg/d BAPN subcutaneous injection(group?)and control group(group?).We compared the three methods of drug administration,and observed the success rate of the model and the survival rate of the rats.The group with the highest success rate and survival rate was chosen for further study.For terminal measurements,the mean arterial pressure(MAP)and heart rate(HR)were monitored in conscious rats using a noninvasive computerized tail-cuff system.The SNA was assessed through recording the variation in arterial pressure in response to hexamethonium application.Pathological changes in the aortic wall were observed by histological staining.Results: In the acute experiment,the RSNA was significantly elevated after 1 hour of BAPN administration when compared with the control group.In the chronic experiment,the average body weights of group?,?,?,?were 200.5±21.9 g,101.8±32.6 g,114.1±39.1 g and 262.2±8.1g by the end of the 4-week experiment.Among the three drug administrated groups,the survival rates after 4 weeks of drug intervention were 80%,50%,and 80% respectively,and the success rates of AD modeling(including death cases due to AD)were 20%,60%,and 70%,respectively.The rate of AD formation and survival rate were the highest in group?.The SNA of rats treated with subcutaneous administration of group? was significantly higher than that of the control group.Conclusion: In this experiment,we demonstrated that subcutaneous administration of 666mg/kg/d BAPN is an effective method for AD formation in rats.SNA of the rats was significantly increased in the short term after intraperitoneal injection of BAPN.The BAPN-induced AD model rats were also showed the elevation of SNA.This animal model could be used for the study of the relationship between SNA and the formation of AD.Part? The effect of bilateral superior cervical ganglionectomy on the progression of ?-aminopropionitrile-induced aortic dissection in ratsBackground: The mechanism of aortic dissection(AD)formation shows considerable complexity,and the exact mechanism is still unclear.AD is due to a tear in the intimal layer of the aorta,which commonly is preceded by medial wall degeneration or cystic media necrosis.The sympathetic nervous system(SNS)is known to play an important role in regulation of different functions of the cardiovascular system.Sympathetic ganglion block(SGB)has been reported to attenuate the severity of symptoms and slowed the progression of several cardiovascular diseases including ventricular arrhythmias and pulmonary arterial hypertension.Clinical studies have shown that the the sympathetic nerve over-activity may be associated with the formation of AD.Our previous study showed that SNA was significant enhancement in ?-aminopropionitrile(BAPN)treated rats.We speculate that the progression of AD may be attenuated by reducing SNA.Object: In this study,we examined the effects of bilateral superior cervical ganglionectomy(SCGx)on the progression of BAPN-induced AD in rats.Materials and methods: Forty Sprague–Dawley rats were randomly divided into three groups: BAPN(n=15),BAPN+SCGx(n=15)and control groups(n=10).The success rate of the model and the survival rate of rats were observed.BAPN drug was administered by subcutaneous injection of 666mg/kg/d BAPN for a total of 4 weeks.For terminal measurements,the arterial blood pressure(ABP)and heart rate(HR)were monitored and the basal SNA was assessed through recording the variation in arterial pressure in response to hexamethonium application.Pathological changes in the aortic wall were observed by histological staining.Matrix metalloproteinase-2(MMP-2)and MMP-9 concentrations within the aortic wall were analyzed by western blot.Results: The results show that BAPN administration could elevate SNA and cause the formation of AD in rats with a high incidence(67.7%),while SCGx treatment inhibited the elevation of SNA and significantly reduced the incidence(20%).There was no significant difference in blood pressure between the three groups,but the HR in the BAPN group was significantly higher than that in the BAPN+SCGx group.The concentrations of MMP-2 and MMP-9 in aortic wall tissue were increased by the administration of BAPN when compared with control rats.SCGx treatment attenuated this finding and was showed to be of statistical significance for MMP-9.Conclusion: SCGx may suppress the formation of BAPN-induced AD via restraining the rise of HR and reducing the MMP-9 concentration in aortic wall.These results indicate that surgical techniques such as sympathetic nerve block may be a potentially useful therapy for the prevention of AD.