Abstract
BackgroundMechanisms of positive effects of pulmonary artery (PA) denervation (PADN) remain poorly understood. The study aimed to evaluate pulmonary hemodynamic changes after PADN and their association with the extent of PA wall damage in an acute thromboxane A2 (TXA2)-induced pulmonary hypertension (PH) model in swine.MethodsIn this experimental sham-controlled study, 17 normotensive male white Landrace pigs (the mean weight 36.2 ± 4.5 kg) were included and randomly assigned to group I (n = 9)—PH modeling before and after PADN, group II (n = 4)—PADN only, or group III (n = 4)—PH modeling before and after a sham procedure. Radiofrequency (RF) PADN was performed in the PA trunk and at the proximal parts of the right and left PAs. PA wall lesions were characterized at the autopsy study using histological and the immunohistochemical examination.ResultsIn groups I and II, no statistically significant changes in the mean pulmonary arterial pressure nor systemic blood pressure were found after PADN (−0.8 ± 3.4 vs 4.3 ± 8.6 mmHg, P = 0.47; and 6.0 ± 15.9 vs -8.3 ± 7.5 mmHg, P = 0.1; correspondingly). There was a trend towards a lower diastolic pulmonary arterial pressure after PADN in group I when compared with group III during repeat PH induction (34.4 ± 2.9 vs 38.0 ± 0.8; P = 0.06). Despite the presence of severe PA wall damage at the RF application sites, S100 expression was preserved in the majority of PA specimens. The presence of high-grade PA lesions was associated with HR acceleration after PADN (ρ = 0.68, p = 0.03). No significant correlation was found between the grade of PA lesion severity and PA pressure after PADN with or without PH induction.ConclusionsExtended PADN does not affect PH induction using TXA2. Significant PA adventitia damage is associated with HR acceleration after PADN. Possible delayed effects of PADN on perivascular nerves and pulmonary hemodynamics require further research in chronic experiments.
Highlights
Mechanisms of positive effects of pulmonary artery (PA) denervation (PADN) remain poorly understood
Pulmonary artery denervation in group I (PH‐pulmonary artery denervation (PADN)) Hemodynamic parameters at baseline, and during pulmonary hypertension (PH) induction-1 and PH-induction-2 are presented in Additional file 1: Table S1
thromboxane A2 (TXA2) infusion was characterized by a dose-dependent target mean pulmonary artery pressure (mPAP) elevation due to significant pulmonary vascular resistance (PVR) increase and accompanied with Cardiac output (CO) reduction
Summary
Mechanisms of positive effects of pulmonary artery (PA) denervation (PADN) remain poorly understood. The study aimed to evaluate pulmonary hemodynamic changes after PADN and their association with the extent of PA wall damage in an acute thromboxane A2 (TXA2)-induced pulmonary hypertension (PH) model in swine. Several clinical studies have demonstrated a substantial improvement in pulmonary hemodynamics and exercise capacity after pulmonary artery denervation (PADN) in patients with different etiologies of pulmonary hypertension (PH) [3,4,5,6,7,8], identifying interventional or surgical PADN as an attractive additional PH treatment option [9,10,11,12,13]. Hemodynamic effects should be interpreted with caution since acute models do not resemble chronic pulmonary arteries remodeling, and chronic models have different pathophysiology compared to humans [14]. Acute stable controlled but reversible TXA2induced PH could be a relevant type of PH modeling for acute PADN effects assessment
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