The Effects Of Pulmonary Artery’s Denervation Cryoablation On Dehydrogenized-monocrotaline-induced Pulmonary Arterial Hypertension In Dogs And Its Potential Mechanism

Background:Pulmonary arterial hypertension(PAH)is a group of diseases characterized by gradual increase of pulmonary vascular resistance leading to right heart failure and premature death.Although significant progress has been made in treatment,there are still problems to be solved.Drug treatment is costly and resistant,so it is important to explore other treatments.Due to the important role of sympathetic overactivation in PAH development,most surgical procedures focus on the suppression of sympathetic nerves.Purpose:The purpose of this study is to investigate the effect of a new surgical method of pulmonary artery’s denervation cryoablation in the treatment of pulmonary hypertension.Methods:Forty male beagles(body weight 10-15 kg)were randomly divided into two groups:Control group(10 dogs)and experimental group(30 dogs).In the experimental group,2mg/kg of dehydromonocylline(DHMCT)was injected into the right atrium of dogs,while in the control group,2mg/kg of dimethylamide solution was injected into the right atrium of dogs.After 8 weeks,pulmonary artery occlusion pressure(PAOP),pulmonary systolic pressure(PASP),mean pulmonary artery pressure(MPAP),right ventricular systolic pressure(RVSP),mean right ventricular pressure(MRVP),cardiac output(CO)and pulmonary vascular resistance(PVR)were measured by right cardiac catheterization in each group to determine whether the modeling was successful.27 dogs in the experimental group were determined to be successful in modeling(mean pulmonary arterial pressure greater than or equal to 25mmHg),and then randomly divided into 3 groups:DHMCT group(n=9),DHMCT+pulmonary artery’s denervation cryoablation group(n=9),DHMCT+Sham group(n=9),and DHMCT+Sham group(n=9).At baseline,8 weeks and 14 weeks,right cardiac catheterization and color Doppler ultrasonography were performed,and plasma was collected.After 14 weeks,the experimental animals were euthanized,and the lung tissues were collected for histomorphology,q-PCR,and ELISA tests.Results:(1)At week 8,the levels of MPAP,PASP,PVR,PAOP,RVSP and MRVP in DHMCT,DHMCT+SHAM and DHMCT+CB groups were significantly higher than those in Control group.CO was significantly lower than that in Control group,indicating that PAH model was successfully constructed.(2)At week 14,after CB surgery,MPAP,PVR,PAOP,PASP,and right ventricular function were significantly lower than those in the DHMCT and DHMCT+SHAM groups:In the DHMCT+CB group,MPAP,PVR,PAOP,PASP,and right ventricular function were improved at 14 weeks compared with 8 weeks.(3)Compared with DHMCT+Sham group and DHMCT group,cryoballoon sympathetic removal of pulmonary artery significantly reduced the percentage of Wall thickness of pulmonary artery Wall%,collagen deposition,and myalized pulmonary arteriole(FM).Meanwhile,the levels of norepinephrine(NE),angiotensin Ⅱ(ANGII)and endothelin 1(ET-1)in pulmonary artery tissues were decreased.(4)Freezing balloon removal of pulmonary artery sympathetic nerve reduced the increase of inflammatory cytokines IL-1α,IL-1β PDGF-BB,TNF-α,VEGF,FGF2 levels induced by DHMCT.Conclusion:The results of this study suggest that pulmonary artery’s denervation cryoablation may improve pulmonary hypertension,right ventricular dysfunction,right ventricular dilatation,hypertrophy,and right heart failure caused by monocerine to some extent.This procedure is expected to be a potential effective treatment option for PAH.In this study,the number of experimental animals is small and the species of experimental animals is single.In future research,more kinds of animals need to be included for experimental research.