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

Renal artery denervation (RDN) has been proposed for resistant arterial hypertension. Beyond conventional radiofrequency (RF) ablation, there are emerging RDN technologies, including laser catheter ablation. We aimed at evaluamting the local effects of laser ablation on the renal artery and perivascular nerve injury in comparison with radiofrequency ablation. Thirteen pigs (mean weight 36.7 ± 4.7 kg, age 3 months) were divided into three groups: (1) laser ablation in normotensive pigs (LA; n = 3), (2) bipolar RF ablation in normotensive pigs (RF; n = 7), and (3) a sham group (SHAM; n = 3). Transcatheter laser and RF ablations were performed under general anesthesia. After euthanasia, pathology and immunohistochemical studies were performed. Artery wall and perivascular nerve lesions were found in the LA and RF groups. A lower rate of intimal microdissections was evaluated after laser ablation when compared with RF ablation (0 vs. 1.5 [1;2.75] per artery; p < .05). There was a numerical prevalence of nerves with tyrosine hydroxylase expression loss after laser RDN when compared with RF ablation (16.7 [4; 18] vs. 9.1 [0;18] per specimen). Laser ablation is noninferior to RF ablation regarding perivascular nerve injury and is associated with less intimal layer damage.

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

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.

Pulmonary and Systemic Hemodynamics following Multielectrode Radiofrequency Catheter Renal Denervation in Acutely Induced Pulmonary Arterial Hypertension in Swine.

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.

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

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.

Stimulation Mapping of the Pulmonary Artery for Denervation Procedures: an Experimental Study.

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.

Extended Renal Artery Denervation Is Associated with Artery Wall Lesions and Acute Systemic and Pulmonary Hemodynamic Changes: A Sham-Controlled Experimental Study.

OBJECTIVES: We sought to assess acute changes in systemic and pulmonary hemodynamics and microscopic artery lesions following extended renal artery denervation (RDN). BACKGROUND: RDN has been proposed to reduce sympathetic nervous system hyperactivation. Although the effects of RDN on systemic circulation and overall sympathetic activity have been studied, data on the impact of RDN on pulmonary hemodynamics is lacking. METHODS: The study comprised 13 normotensive Landrace pigs. After randomization, 7 animals were allocated to the group of bilateral RDN and 6 animals to the group of a sham procedure (SHAM). Hemodynamic measures, cannulation, and balloon-based occlusion of the renal arteries were performed in both groups. In the RDN group, radiofrequency ablation was performed in all available arteries and their segments. An autopsy study of the renal arteries was carried out in both groups. RESULTS: The analysis was performed on 12 pigs (6 in either group) since pulmonary thromboembolism occurred in one case. A statistically significant drop in the mean diastolic pulmonary artery pressure (PAP) was detected in the RDN group when compared with the SHAM group (change by 13.0 ± 4.4 and 10.0 ± 3.0 mmHg, correspondingly; P = 0.04). In 5 out of 6 pigs in the RDN group, a significant decrease in systemic systolic blood pressure was found, when compared with baseline (98.8 ± 17.8 vs. 90.2 ± 12.6 mmHg, P = 0.04), and a lower mean pulmonary vascular resistance (PVR) (291.0 ± 77.4 vs. 228.5 ± 63.8 dyn∗sec∗cm-5, P = 0.03) after ablation was found. Artery dissections were found in both groups, with prevalence in animals after RDN. CONCLUSIONS: Extensive RDN leads to a rapid and significant decrease in PAP. In the majority of cases, RDN is associated with an acute lowering of systolic blood pressure and PVR. Extended RDN is associated with artery wall lesions and thrombus formation underdiagnosed by angiography.

The Ca2+ -Regulated Photoprotein Obelin as a Tool for SELEX Monitoring and DNA Aptamer Affinity Evaluation.

Bioluminescent solid-phase analysis was proposed to monitor the selection process and to determine binding characteristics of the aptamer-target complexes during design and development of the specific aptamers. The assay involves Ca2+ -regulated photoprotein obelin as a simple, sensitive and fast reporter. Applicability and the prospects of the approach were exemplified by identification of DNA aptamers to cardiac troponin I, a highly specific early biomarker for acute myocardial infarction. Two structurally different aptamers specific to various epitopes of troponin I were obtained and then tested in a model bioluminescent assay.

Electrical Stimulation-Guided Approach to Pulmonary Artery Catheter Ablation in Patients with Idiopathic Pulmonary Arterial Hypertension: A Pilot Feasibility Study with a 12-Month Follow-Up.

BACKGROUND: Recently, transcatheter pulmonary artery (PA) ablation aiming at sympathetic denervation has been proposed in pulmonary arterial hypertension (PAH). This pilot feasibility study aimed to assess the feasibility of selective radiofrequency PA ablation based on response to high-frequency stimulation mapping. METHODS: The study comprised 3 female patients with idiopathic PAH (IPAH). The following reactions to PA stimulation were noted and marked by color points on the three-dimensional map: sinus bradycardia (heart rate decrease ≥15%), tachycardia (heart rate increase ≥15%), phrenic nerve capture, and cough. Since the most appropriate ablation strategy was unknown, two approaches were suggested, according to stimulation results: ablation at points with any heart rate response (either bradycardia or tachycardia)-this approach was applied in patient #1 (IPAH long-term responder to calcium channel blockers); segmental ablation at points with no response and with tachycardia response (one IPAH long-term responder to calcium channel blockers patient and one-IPAH with negative vasoreactive testing). Hemodynamic measurements were performed before and after denervation. Follow-up visits were scheduled at 6 and 12 months. RESULTS: Six-months follow-up was uneventful for patients #1 and 3; patient #2 had one syncope and reduced 6-minute walk test distance and peak VO2 consumption. At 12 months, there was a normalization of mean PA pressure and pulmonary vascular resistance (PVR) in patient #1. Patient #2 had no change in PA pressure and PVR at 12 months. Patient #3 remained in II functional class; however, there was an increase in mean PA pressure and loss of vasoreactivity. CONCLUSIONS: Electrical high-frequency stimulation of the PA identifies several types of evoked reactions: heart rate slowing, acceleration, phrenic nerve capture, and cough. The improvement in clinical and hemodynamic parameters following targeted PA ablation in the IPAH patient with positive vasoreactive testing should be confirmed in larger studies.