Nerve Distribution Of Canine Pulmonary Arteries And Potential Clinical Implications

BACKGROUND:Pulmonary artery hypertension(PAH) is a complex vascular remodeling disease, characterized by medium-sized and small pulmonary arteries with medial and adventitial hypertrophy and intimal proliferative changes. It contributes to increased pulmonary vascular resistance, leading to heart failure and death. PAH is multifactorial: It is unlikely that one factor or gene mutation can explain all forms of PAH. The currently approved therapies neither improve survival nor reverse the progression of the disease. Moreover, current therapies lack specificity for pulmonary vessels, as all of these therapies originated for the treatment of systemic vascular disease. The overall effect of the current therapies on hemodynamics and functional capacity is minimal, and thus new therapeutic strategies are urgently needed in the near future. Velez-Roa et al. reported an increase in sympathetic nerve activity in patients with PAH, potentially promoting the progression of PAH. Although current PAH therapy focuses on reversing the imbalance between vasoconstrictors and vasodilators, it does not significantly improve survival. Recently, the First-in-Man PADN-1 study showed that percutaneous pulmonary artery denervation(PADN) could reduce pulmonary artery pressure(PAP) and pulmonary vascular resistance(PVR) due to injury to the main pulmonary artery bifurcation area, improving cardiac function and functional capacity of patients with idiopathic PAH. An increasing number of studies have showed that sympathetic nerve activity increases in PAH, with the severity and prognosis of PAH correlated to sympathetic nerve activity. It has been realized that sympathetic activation plays an important pathophysiological role in the progressive of patients with pulmonary artery hypertension(PAH). Although adrenergic vasomotor fibers are identified in the adventitial of the pulmonary arteries, the anatomy of peri-arterial pulmonary nerves is still poorly understood.OBJECTIVE:The aim of the present study was to examine the anatomic characteristics of canine pulmonary artery nerves with respect to density, size, and distance from the pulmonary artery lumen intima, and to discuss the potential therapeutic targets for PADN.METHODS:Pulmonary trunk, the bifurcation and the equal proximal, middle, distal segment of the bilateral pulmonary artery were collected from 6 dogs. Sympathetic and vagus nerve was investigated by immunofluorescence staining using antibodies targeted for anti–tyrosine hydroxylase and anti–choline acetyltransferase.RESULTS:A total of 2160 sympathetic nerves were identified in six Chinese Kunming canines. Nerve counts were greatest in the proximal segment, with a slight decrease in the distal segment; the middle segment showed the least number of nerves. In the left and right pulmonary arteries, 77.61% and 78.97% of the nerves were located within a 1–3-mm range, respectively. The number of nerves in the posterior region of the bifurcation and pulmonary trunk outnumbered those in the anterior region. Furthermore, 65.33% of the nerves were located in the first 2-mm range of the posterior region of bifurcation, and 89.62% of the nerves were located within the 1–3-mm range of the posterior region of the pulmonary trunk.CONCLUSION:A great abundance of sympathetic nerves occurred in the proximal and distal segments of the bilateral pulmonary arteries. There is a clear predominance of sympathetic nerve distribution in the posterior region of the bifurcation and pulmonary trunk. This anatomic distribution may have implications for the future development of percutaneous pulmonary artery denervation.