The study of selective percutaneous pulmonary artery denervation guided by high-frequency stimulation for monocrotaline-induced porcine pulmonary arterial hypertension

Percutaneous pulmonary artery denervation has recently emerged as a potential therapeutic approach for pulmonary arterial hypertension (PAH). This study aims to investigate the feasibility of selective pulmonary artery denervation guided by high-frequency stimulation mapping. Fifteen Luchuan pigs, weighing approximately 30 kg (Harbin Scientia Biotechnology Corporation, China), were randomly divided into two groups: a control group (Con group, n = 5) and an experimental group ( n = 10). The experimental group received two intraperitoneal injections of 1% monocrotaline (MCT) solution (MCE, USA) at a dose of 20 mg/kg, administered at a one-week interval. The Con group received an equivalent volume of 75% alcohol as a vehicle control. At week 7, all animals underwent right heart catheterization (RHC). The successful establishment of the PAH-like pulmonary vascular disease model was confirmed by mPAP ≥ 20 mmHg. Subsequently, the experimental group was randomly subdivided into two groups ( n = 5 per group): a sham-operated PAH group (PAH-nonSPADN group) and a SPADN group. In the SPADN group, at 7 weeks following the initial MCT injection, SPADN was carried out. Sites exhibiting a rise in systolic pulmonary artery pressure of ≥ 5 mmHg during stimulation were designated as "hot spots" for ablation (stimulation: 20 Hz, 10 mV, 10 ms pulse width; ablation: 20 W, 120 s). while the PAH-nonSPADN group received a sham operation at the same time point. Upon completion of all measurements, the animals were euthanized. Lung and right ventricular tissue samples were harvested. At week 7, both the PAH-nonSPADN and SPADN groups exhibited significantly elevated mean pulmonary artery pressure (mPAP) compared to the Con group [(27.00 ± 1.50) mmHg and (28.88 ± 1.99) mmHg vs. (16.20 ± 0.77) mmHg, P < 0.01], confirming successful model establishment. At 6 months post-procedure, the SPADN group showed significant improvements in mPAP, mean right atrial pressure, mean right ventricular pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, and cardiac output compared to the PAH-nonSPADN group ( P < 0.01). Furthermore, within the SPADN group, mPAP and cardiac output were significantly improved at 6 months compared with week 7 ( P < 0.05). Histopathological analysis revealed that, compared to the Con and SPADN groups, the PAH-nonSPADN group exhibited pronounced pulmonary vascular thickening, luminal stenosis, and a significantly increased percentage of collagen-positive area in the right ventricle. Notably, the SPADN group demonstrated a significant reduction in both the pulmonary vascular wall thickness to external diameter ratio [(38.32% ± 6.75%) vs. (55.78% ± 3.89%), P < 0.01] and the right ventricular collagen fiber area percentage [(4.46% ± 0.61%) vs. (9.28% ± 0.83%), P < 0.01] compared to the PAH-nonSPADN group. No serious adverse events were observed in any of the operated animals. In the porcine model of MCT-induced PAH-like pulmonary vascular disease, high-frequency stimulation-guided selective percutaneous pulmonary artery denervation may effectively reduces pulmonary artery pressure, ameliorates right ventricular dysfunction, dilation, and hypertrophy, thereby delaying the progression of PAH.