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去交感神经支配犬肺动脉后脱水单硝酸野百合碱诱导肺动脉模型的形态计量学和功能分析。

Sympathetic innervation of canine pulmonary artery and morphometric and functional analysis in dehydromonocrotaline-induced models after pulmonary artery denervation.

机构信息

Department of Cardiovascular Research, Nanjing Medical University, Nanjing, China.

Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

出版信息

Interact Cardiovasc Thorac Surg. 2020 Nov 1;31(5):708-717. doi: 10.1093/icvts/ivaa166.

DOI:10.1093/icvts/ivaa166
PMID:33057705
Abstract

OBJECTIVES

We aimed to describe the anatomic distribution of periarterial pulmonary sympathetic nerves and to observe the long-term morphometric and functional changes after pulmonary artery denervation (PADN), a novel therapy for pulmonary arterial hypertension (PAH).

METHODS

A total of 45 beagles were divided into a sympathetic innervation group (n = 3, 33.3% were females), a PAH group (n = 35, 34.3% were females) and a control group (n = 7, 28.5% were females). The PAH group was randomly divided into no-PADN (n = 7), instant-PADN (n = 7), 1M-PADN (n = 7), 2M-PADN (n = 7) and 3M-PADN (n = 7) subgroups. The sympathetic innervation group was sacrificed to reveal the sympathetic innervation of pulmonary arteries. PAH was induced by injecting dehydromonocrotaline (DHMCT) through the right atrium. The pulmonary capillary wedge pressure, right ventricular systolic pressure, right ventricular mean pressure, pulmonary artery systolic pressure and pulmonary artery mean pressure of each group were continuously measured. The cardiac output was detected to calculate the pulmonary vascular resistance. PAH and control groups were subjected to immunofluorescence assay, sympathetic nerve conduction velocity measurement and transmission electron microscopy.

RESULTS

The no-PADN group had significantly higher PVSP, PVMP, pulmonary artery systolic pressure, pulmonary artery mean pressure and pulmonary vascular resistance but lower cardiac output than those of the control group (P < 0.05). Instant-PADN, 1M-PADN, 2M-PADN and 3M-PADN groups had significantly lower PVSP, PVMP, pulmonary artery systolic pressure, pulmonary artery mean pressure and pulmonary vascular resistance but higher cardiac output than those of the no-PADN group (P < 0.05). Most sympathetic nerves were located within 2.5 mm of the intimae of the bifurcation and proximal trunk, mainly in the left trunk. The diameter and cross-sectional area of myelinated fibres in the PAH group were significantly larger than those of the control group. Sympathetic nerve conduction velocity of the PAH group gradually decreased, and nerve fibres were almost demyelinated 3 months after PADN.

CONCLUSIONS

PADN effectively relieved dehydromonocrotaline-induced canine PAH and decreased sympathetic nerve conduction velocity.

摘要

目的

描述肺周围动脉交感神经的解剖分布,并观察肺动脉去神经(PADN)后长期的形态计量和功能变化,这是肺动脉高压(PAH)的一种新疗法。

方法

将 45 只比格犬分为交感神经支配组(n=3,33.3%为女性)、PAH 组(n=35,34.3%为女性)和对照组(n=7,28.5%为女性)。PAH 组随机分为无-PADN(n=7)、即刻-PADN(n=7)、1M-PADN(n=7)、2M-PADN(n=7)和 3M-PADN(n=7)亚组。处死交感神经支配组以揭示肺动脉的交感神经支配。通过右心房注射脱水单环毛茛碱(DHMCT)诱导 PAH。连续测量各组的肺毛细血管楔压、右心室收缩压、右心室平均压、肺动脉收缩压和肺动脉平均压。检测心输出量以计算肺血管阻力。PAH 组和对照组进行免疫荧光测定、交感神经传导速度测定和透射电镜检查。

结果

无-PADN 组的肺动脉收缩压、肺动脉平均压、肺动脉收缩压、肺动脉平均压和肺血管阻力明显高于对照组(P<0.05),心输出量明显低于对照组(P<0.05)。即刻-PADN、1M-PADN、2M-PADN 和 3M-PADN 组的肺动脉收缩压、肺动脉平均压、肺动脉收缩压、肺动脉平均压和肺血管阻力明显低于无-PADN 组(P<0.05),心输出量明显高于无-PADN 组(P<0.05)。大多数交感神经位于分叉和近端干的内膜 2.5mm 以内,主要位于左干。PAH 组有髓纤维的直径和横截面积明显大于对照组。PAH 组的交感神经传导速度逐渐降低,PADN 后 3 个月神经纤维几乎脱髓鞘。

结论

PADN 有效缓解脱水单环毛茛碱诱导的犬 PAH,降低交感神经传导速度。

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