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

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.

Keywords: Dehydromonocrotaline; Denervation; Pulmonary artery; Sympathetic innervation.