An Ovine Model for Percutaneous Pulmonary Artery Laser Denervation: Perivascular Innervation and Ablation Lesion Characteristics

Abstract

Background: Pulmonary artery denervation (PADN) is an evolving interventional procedure capable to reduce pulmonary artery (PA) pressure. We aimed to compare PA nerve distribution in different specimens and assess the feasibility of an ovine model for a denervation procedure and evaluate the acute changes induced by laser energy. Methods: The experiment was divided into two phases: (1) the analysis of PA nerve distribution in sheep, pigs, and humans using histological and immunochemical methods; (2) fiberoptic PADN in sheep and postmortem laser lesion characteristics. Results: PA nerve density and distribution in sheep differ from humans, although pigs and sheep share similar characteristics, nerve fibers are observed in the media layer, adventitia, and perivascular tissue in sheep. Necrosis of the intima and focal hemorrhages within the media, adventitia, and perivascular adipose tissue were evidenced post laser PADN. Among the identified lesions, 40% reached adventitia and could be classified as effective for PADN. The use of 20 W ablation energy was safer and 30 W-ablation led to collateral organ damage. Conclusions: An ovine model is suitable for PADN procedures; however, nerve distribution in the PA bifurcation and main branches differ from human PA innervation. Laser ablation can be safely used for PADN procedures.

Transcatheter radiofrequency pulmonary artery denervation in swine: the evaluation of lesion degree, hemodynamics and pulmonary hypertension inducibility

“…In the animals after PADN (PH-PADN and nonPH-PADN groups, n = 10), RF-induced PA lesions were inhomogeneous (Fig. 5 ), here fore, a semi-quantitative grading system for each detected RF lesion was applied (Additional file 1 : Table S2) [ 22 ]. The percentages of the lesion grades are presented in Additional file 1 : Table S3.…”

“…Another issue is RF-induced PA wall injury with subsequent PA remodeling as well as the concomitant damage of parasympathetic nerve fibers that lie together with sympathetic ones [ 21 , 32 ] and mediate the PA vasodilatation effect [ 33 ]. Various types of micro-injuries including PA wall dissection, coagulation of media and adventitia, parietal thrombosis, and hemorrhages in different layers at the sites of RF applications and adjacent areas have been revealed on pathomorphological examination in swine [ 22 , 27 ]. In chronic PVH, no significant PA wall changes have been noted 3 months after transcutaneous RF PADN [ 17 ].…”

“…At the sites of identified RF lesions, the pulmonary artery was cut into rings (width 1 cm) which included a non-damaged area around the lesions. Each detected lesion was classified into grades I, II or III according to a previously published description [ 22 ]. The percentage of RF-induced lesions was calculated according to the following description: the area of a PA lesion divided by the total area of a PA ring specimen *100%.…”

Laser renal denervation: A comprehensive evaluation of microstructural renal artery lesions

“…Therefore, laser RDN in three animals would result in about 150–200 nerves damaged (2 arteries and 2 applications per artery). Based on our preliminary experimental data, laser ablation in middle‐sized arteries resulted in almost circumferential lesions, whereas bipolar RF ablation had spot‐like lesions with a limited area of damage (Condori Leandro, 2021; Sagerer‐Gerhardt, 2021; Vakhrushev, 2021). Therefore, bipolar RF ablation required 3–4 times more applications than laser ablation to achieve the same area of damage, and the number of renal arteries in the RF ablation group would need to be larger by at least 2 times.…”

Device-Based Sympathetic Nerve Regulation for Cardiovascular Diseases

“…The nMARQ loop ablation catheter (Biosense Webster Inc., Diamond Bar, CA) is another multi-electrode ablation device for which a feasibility study for PADN application (NCT02403908) is underway. Recently, an animal trial reported the use of laser energy for PADN and confirmed sympathetic nerve destruction in the pulmonary artery on histopathological examination, providing a new idea for PADN ( 121 ). In addition to the above regulation modalities, study has also reported the use of chemical drugs for PADN ( 122 ), but the currently used 6-hydroxydopamine can lead to cardiac autonomic dysregulation and myocardial injury ( 122 ), and is difficult to use in clinical practice.…”