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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.

Objective. We aimed to assess the effects of renal denervation (RDN) on systemic and pulmonary hemodynamics in a swine model of thromboxane A2- (TXA2-) induced pulmonary arterial hypertension (PAH). Methods. The study protocol comprised two PAH inductions with a target mean pulmonary artery pressure (PAP) of 40 mmHg at baseline and following either the RDN or sham procedure. Ten Landrace pigs underwent the first PAH induction; then, nine animals were randomly allocated in 1 : 1 ratio to RDN or sham procedure; the second PAH induction was performed in eight animals (one animal died of pulmonary embolism during the first PAH induction, and one animal died after RDN). In the RDN group, ablation was performed in all available renal arteries, and balloon inflation within artery branches was performed in controls. An autopsy study of the renal arteries was performed. Results. At baseline, the target mean PAP was achieved in all animals with 25.0 [20.1; 25.2] mcg of TXA2. The second PAH induction required the same mean TXA2 dose and infusion time. There was no statistically significant difference in the mean PAP at second PAH induction between the groups ( 39.0 ± 5.3 vs. 39.75 ± 0.5  mmHg, P > 0.05 ). In the RDN group, the second PAH induction resulted in a numerical but insignificant trend toward a decrease in the mean systemic blood pressure and systemic vascular resistance, when compared with the baseline induction ( 74 ± 18.7 vs. 90.25 ± 28.1  mmHg and 1995.3 ± 494.3 vs. 2433.7 ± 1176.7   d y n ∗ sec ∗ c m − 5 , P > 0.05 , respectively). No difference in hemodynamic parameters was noted in the sham group between the first and second PAH induction. Autopsy demonstrated artery damage in both groups, but RDN resulted in more severe lesions. Conclusions. According to our results, RDN does not result in significant acute pulmonary or systemic hemodynamic changes in the TXA2-induced PAH model. The potential chronic effects of RDN on PAH require further research.

Background 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. Methods In 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. Results In 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. Conclusions Extended 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.

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Aim. To study and compare the lesions characteristics of laser energy in heart ex vivo and in experimental large animals.Materials and methods. For the ex vivo experiment a pig heart was obtained from a local slaughterhouse. Laser applications were applied using power 15-30 W in the left and right ventricles 5-50 seconds in duration. Immediately after ablation, examination was performed to determine myocardial damage characteristics at each point. In the experimental study, 7 sheep were included, laser applications were performed under fluoroscopic control in the right atrium with power 10, 15 and 20 W, 10-25 s; in the right ventricle 20, 25 and 30 W for 10-40 s; and in the left ventricle 20, 25 and 30 W for 20-40 s. The animals were euthanized and macroscopic examination of laser lesions was performed.Results. A total of 27 laser applications were performed on the heart ex vivo, all lesions were visualized as white spots on the endocardial surface. The maximum lesion depth was 9 mm achieved when using 20 W /50 s, the maximum lesion diameter was 6 mm, when using 25 W /40 s. The minimum lesion diameter and depth were observed when using 30 W /5 s, 2x1 mm. A total of 48 laser applications were performed in experimental animals, in one experimental animal was observed a transmural lesion in the right atrium when using 15 W /20 s. In 3 out of 7 experimental animals, transmural lesions were observed in the right ventricle when using 20 W /30 s; 20 W /40 s and 30 W /10 s. In the left ventricle, transmural lesions were observed in 2 animals, using 15 W /20 s and 20 W /40 s. In the ex vivo study, there was a strong positive correlation between ablation energy and lesion depth (R=0.91, P<0.05) and lesion volume (R=0.73, P<0.05); while there was no such statistical correlation in vivo.Conclusions. Laser ablation 15-20 W for 15-40 s seems to be optimal for achieving the deepest lesions in the atrium and ventricular myocardium. In our small pilot study with fiberoptic catheter ablation on a beating heart there was no correlation between energy delivered and the depth and volume of necrotic myocardium.

Background/Introduction Pulmonary artery denervation (PADN) is an interventional procedure aiming to modulate and correct pulmonary artery (PA) pressure. New technologies and energy sources are being tested currently. However, the effects of laser energy on the PA wall are unknown. Purpose To assess the acute effects and impact of laser energy for PADN procedure in normotensive sheep by applying different power settings and session times. Methods A total of 10 normotensive Katumsky sheep were included in the experiment. Percutaneous vascular access was performed under general anesthesia. A fiberoptic open-irrigated non-steerable catheter was introduced via a femoral vein through a steerable sheath. Laser applications were applied in the PA trunk and the proximal areas of the right and left PA under fluoroscopic guidance with a 5mm distance between points in the anterior, posterior and lateral walls. Applications were delivered with power 10–30W, 10–35s in duration; irrigation flow 40ml/min. After the procedure, experimental animals were euthanized and underwent an autopsy. PA samples were obtained regardless of the absence of visible laser-related lesions for histological analysis (hematoxylin staining) and immunohistochemical labelling (S100). Results A total of 108 ablation sessions were performed, 33 in the right PA, 30 in the left PA and 42 in the PA trunk. During macroscopic examination, laser-related lesions described as irregular brown hemorrhage spots and rough defects observed in the PA endothelium were not homogenous in all experimental animals. Thermal injuries either in the left or right lung lobes were identified in 5 (50%) experimental animals when using 30W during 10–20sec. In 5 (50%) sheep no collateral lung injuries were identified when using 10–20W from 20–35s. A total of 64 PA fragments underwent microscopic examination, acute thermal tissue lesions were observed in all experimental animals despite the absence of laser-related lesions in the PA endothelium; dissection, edema, disruption trough tunica layers, hemorrhage and necrosis at different depth walls. The most frequent nerve damage was obtained with 20W ablation: 5/8 PAs vs, 1/6 with 10–15W and 1/14 with 25–30W (P=0.01). At the same time, there was no difference in intima necrosis between the groups (1/6, 2/8 and 4/14 for 10–15, 20 and 25–30W groups, respectively). Conclusion(s) Percutaneous PA laser ablation is feasible, reduction of perivascular nerve expression is seen most frequently, when 20W/20–35 s ablation is performed. PA lesions may differ in depth and characteristics, and perivascular nerve damage might be seen in cases with preserved intima. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant of the Ministry of Science and Higher Education of the Russian Federation

Introduction Pulmonary hemodynamics improvement after pulmonary artery denervation (PADN) was demonstrated in PAH. Questions arise regarding PADN perioperative effectiveness and the accuracy of the target nerves damage. The aim of the study was to evaluate whether PADN decreases pulmonary artery pressure (PAP) in acute thromboxane A2 (U46619)–induced PAH, and damages PA perivascular nerve fibers. Materials and methods 10 male Landrace swine (34.7±5.1 kg). In 6 swine acute reversible target mean PAP of 40 mm Hg was induced with synthetic thromboxane A2 infusion (U46619). Control group: 4 swine with PADN. Hemodynamics was assessed throughout the study, PAH modeling was done before and 20 min after PADN (radiofrequency energy, 40 Watts), followed by pathology and immunohistochemical studies. Results The mean number of RF applications was 17.5±3.6. Pulmonary embolism (PE) was observed after PADN in 3 swine with U46619 infusion, which were excluded. There was no differences in mPAP, PVR and U46619 dosage after PADN in PAH model (12.3±3.5 vs 12.1±1 mm Hg, p=0.2; 150.4±48.7 vs 129.2±64.1 dynes s cm–5; p=0.2; 24.9±3.3 vs 22.4±4.1 mcg; p=0.18; respectively). Similar hemodynamic results were observed in the control group after PADN (mPAP; p=0.3; PVR; p=0.58). S100 expression was evident in the majority of RFA PA species and in some species loss in tyrosine hydroxylase and M1 acetylcholine receptors expression was detected with no hemodynamic correlation. Conclusions PADN using an electrophysiological catheter with unipolar energy does not lead to an acute PA perivascular nerve fibers destruction and detectable mPAP changes in U46619-induced PAH. Delayed nerve damage might be attributable to PADN effects observed in previous studies. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant from the Ministry of Science and Higher Education of the Russian Federation (agreement #075-15-2020-800).