Application Of Pulmonary Artery Denervation By High-intensity Focused Ultrasound In Rabbits

Background: Over-activation of sympathetic nervous system(SNS)plays a vital role in occurrence and progress of pulmonary arterial hypertension(PAH).While pulmonary artery denervation(PADN)can improve hemodynamic and living status via locally destroying structure and function of nerves around pulmonary artery(PA),reducing pulmonary artery pressure(PAP)and pulmonary vascular resistance(PVR).Highintensity focused ultrasound(HIFU)is a novel and non-invasive ablation method,while its effect and feasibility in treating PAH are still uncertain.Aims: Aim of our study is to investigate whether HIFU can be a new therapeutic method of PAH through performing PADN in vitro.Methods:(1)Animal preparation: A total of 12 New Zealand rabbits,of either sex,weighing 2000 to 2500 g,were randomly divided into two groups: control group and PADN group.After rabbits in PADN groups being performed HIFU procedures,all rabbits were injected with selfthrombosis through femoral vein to establish an acute thromboembolic pulmonary arterial hypertension(ATEPAH)rabbit model.(2)Right ventricular diameter(RVD),right atrial diameter(RAD),pulmonary artery diameter(PAD)and so on were measured by doppler echocardiography before and after establishing an ATEPAH rabbit model.(3)Systolic right ventricular pressure(RVP),diastolic RVP and mean RVP were measured via right heart catheterization before and after an ATEPAH rabbit model was established.(4)Movat pentachrome stains was conducted to explore changes of PA,hematoxylin and eosin and immunohistochemical stains against S-100 protein were conducted to investigate changes of nerves around PA.Results:(1)In PADN group,5 rabbits were successfully conducted PADN.Among them,ablation zones were found in PA and right lung at the same time in 4 rabbits.(2)After HIFU procedure,there were no significant differences in PAD,RVD,RAD,PAAT,TAPSE and RVP in two groups(all P > 0.05)before establishing an ATEPAH rabbit model.(3)In Con group,after an ATEPAH rabbit model was built,systolic RVP(After vs.Before:41.01±7.12 vs.26.14±7.12 mm Hg,P < 0.001),diastolic RVP(After vs.Before: 7.34±10.98 vs.2.21±6.73 mm Hg,P < 0.05)and mean RVP(After vs.Before: 23.55 ± 8.29 vs.13.19 ± 6.15 mm Hg,P < 0.001)ascended than before.Besides,RVD,RAD and PAD were all wider,PAAT and TAPSE declined than before(all P < 0.05).(4)After an ATEPAH rabbit model was established,systolic RVP(PADN vs.Con: 29.21±3.25 vs.41.01±7.12 mm Hg,P < 0.05),changes of systolic RVP and mean RVP(all P < 0.05)in PADN group were lower than Con group.(5)Compared with Con group,changes of nerves being obviously damaged were shown,including vacuolization,nuclear pyknosis,nuclear pyknosis.Vascular structure and endothelial cells of PA were intact,vascular smooth muscle cells were arranged neatly.Conclusions:(1)HIFU can destroy nerves around PA and then inhibit over-activation of SNS in the development of acute PAH without significantly influencing structure of PA.(2)HIFU can improve hemodynamic status of an ATEPAH rabbit model via damaging nerves around PA locally,reducing elevated degree of systolic RVP and mean RVP.