RESUMEN
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.
Asunto(s)
Desnervación/métodos , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/cirugía , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/cirugía , Animales , Presión Sanguínea , Ablación por Catéter/métodos , Modelos Animales de Enfermedad , Hemodinámica , Masculino , PorcinosRESUMEN
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.
Asunto(s)
Hipertensión Pulmonar/cirugía , Terapia por Láser/métodos , Arteria Pulmonar/inervación , Anciano , Animales , Desnervación , Modelos Animales de Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Arteria Pulmonar/cirugía , Dosis de Radiación , Ovinos , PorcinosRESUMEN
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 dyn∗sec∗cm -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.
Asunto(s)
Desnervación/métodos , Hemodinámica/fisiología , Hipertensión Arterial Pulmonar/patología , Animales , Presión Arterial , Presión Sanguínea/efectos de los fármacos , Ablación por Catéter/métodos , Catéteres , Hipertensión Pulmonar Primaria Familiar/patología , Hipertensión/fisiopatología , Riñón/fisiopatología , Hipertensión Arterial Pulmonar/metabolismo , Arteria Renal/patología , Porcinos , Simpatectomía/métodosRESUMEN
Transcatheter pulmonary artery denervation (PADN) has been developed for the correction of pulmonary hypertension. We investigated pulmonary artery stimulation mapping and its role in PADN procedures. Artery stimulation was performed in 17 Landrace pigs. Low-frequency stimulation defined areas of ventricular and atrial capture. High-frequency stimulation evoked the following responses: sinus rhythm slowing and/or atrial rhythm acceleration in 59% of animals, phrenic nerve capture in 100%, and laryngeal recurrent nerve capture in 23%. The sites with evoked heart rate responses were marked by discrete radiofrequency ablations (RFA). An autopsy showed nerves in the adventitia and perivascular fat under the RFA sites, and the lack of muscarinic-1, tyrosine hydroxylase, and dopamine-5 receptors' expression. During PADN, areas adjacent to the course of phrenic and recurrent laryngeal nerves should be avoided. RFA at points with heart rate responses leads to the non-reproducibility of evoked reactions and the disappearance of neural markers' expression. Graphical abstract.