Pathological Effects of Pulmonary Vein β‐Radiation in a Swine Model

Pérez‐Castellano, Nicasio; Pérez-Villacastín, Julián; Aragoncillo, Paloma; Fantidis, Panayotis; Sabaté, Manel; García‐Torrent, María Jesús; Prieto, Carlos; Corral, J. M. Ferrero; Moreno, Javier; Fernández‐Ortíz, Antonio; Vañó, Eliseo; Macaya, Carlos

doi:10.1111/j.1540-8167.2006.00462.x

Cited by 12 publications

(15 citation statements)

References 53 publications

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“…The pigs in the sham group underwent the same procedures except that the neurostimulator was not turned on during the experiment. For the pigs in the AF+ ablation group, they were treated with radiofrequency ablation in accordance with the procedures described in Perez‐Castellano . In brief, a P‐32 wire connected to a 2.5‐mm balloon catheter was utilized to provide β‐radiation to the superior wall of the right pulmonary vein (PV) trunk for 30 days.…”

Section: Methodsmentioning

confidence: 99%

Ablation alleviates atrial fibrillation by regulating the signaling pathways of endothelial nitric oxide synthase/nitric oxide via miR‐155‐5p and miR‐24‐3p

Wang

Sun

Ding³

et al. 2018

J of Cellular Biochemistry

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Background: This study aimed to identify the microRNAs implicated in atrial fibrillation (AF) to investigate the molecular mechanisms underlying the role of microRNAs in ablation-based AF treatment. Methods: Real-time polymerase chain reaction (PCR) and microRNA microarrays were utilized to measure the profiles of microRNA expression in AF to identify differentially expressed microRNAs. Enzyme-linked immunosorbent assay, real-time PCR, Western blot analysis, and immunohistochemistry assays were also performed to investigate the regulatory relationships among various factors implicated in AF. Finally, bioinformatic tools and luciferase assays were used to confirm the roles of miR-155-5p, miR-24-3p, endothelial nitric oxide synthase (eNOS), and nitric oxide (NO) in the pathogenesis of AF.Results: We demonstrated that the levels of miR-155-5p and miR-24-3p were greatly reduced in postablation AF patients compared with those AF patients not treated by ablation. Furthermore, the NO level in the AF+ group was much lower than that of the AF− group. Finally, in a swine model of AF, evident upregulation of miR-155-5p and miR-24-3p was found in AF pigs, whereas the ablation treatment reduced the levels of miR-155-5p and miR-24-3p in AF pigs.On contrary, as targets of miR-155-5p and miR-24-3p, the levels of eNOS and NO increased when the expression of miR-155-5p and miR-24-3p decreased.Conclusion: MiR-155-5p and miR-24-3p are involved in the pathogenesis of AF via regulating the expression of eNOS and the production of NO. In addition, ablation treatment helps the recovery from AF by reducing the expression of miR-155-5p and miR-24-3p. K E Y W O R D S ablation, atrial fibrillation, endothelial nitric oxide synthase, expression profiling, microarray, microRNA, nitric oxide 1 | INTRODUCTION As one of the most frequently diagnosed chronic arrhythmia, atrial fibrillation (AF) significantly affects the quality of life of its patients. Triggered by an irregular ventricular rate and the disorder in atrial contraction, AF is featured by a high rate (up to 600 beats/min) of asynchronous depolarization of atrial cells. 1 The prevalence of AF is about 2% in developed countries and the mean age of AF patients is about 80 years old. 2 Although J Cell Biochem. 2019;120:4451-4462.wileyonlinelibrary.com/journal/jcb

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Section: Methodsmentioning

confidence: 99%

Ablation alleviates atrial fibrillation by regulating the signaling pathways of endothelial nitric oxide synthase/nitric oxide via miR‐155‐5p and miR‐24‐3p

Wang

Sun

Ding³

et al. 2018

J of Cellular Biochemistry

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“…5 In their study using 60 Gy of a focal β-source for cardiac tissue ablation, Pérez-Castellano et al described endothelial denudiation, elastic lamina disruption, and pulmonary vein sleeve necrosis in the acute animals studied. 2 It was shown that these alterations progressed to intimal hyperplasia and matured to transmural fibrotic lesions within a follow-up of ≈90 days. …”

Section: X-ray Induced Lesions In Acute and Chronic Studiesmentioning

confidence: 99%

“…Although all studies using ionizing radiation suggest a certain time span is needed, there are considerable divergences in the findings with the exact time-course of lesion creation using ionizing radiation in myocardium remaining unknown. [2][3][4][5] Therefore, finding the accurate doses, the exact time-course of lesion generation, markers indicative for antiarrhythmic lesion creation, as well as for the long-term efficacy, are pivotal questions to be answered in chronic follow-up studies.…”

Section: End Points For Lesion Creationmentioning

confidence: 99%

Atrioventricular Node Ablation in Langendorff-Perfused Porcine Hearts Using Carbon Ion Particle Therapy

Lehmann

Richter

Prokesch

et al. 2015

Circ: Arrhythmia and Electrophysiology

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Background— Particle therapy, with heavy ions such as carbon-12 ( 12 C), delivered to arrhythmogenic locations of the heart could be a promising new means for catheter-free ablation. As a first investigation, we tested the feasibility of in vivo atrioventricular node ablation, in Langendorff-perfused porcine hearts, using a scanned 12C beam. Methods and Results— Intact hearts were explanted from 4 (30–40 kg) pigs and were perfused in a Langendorff organ bath. Computed tomgraphic scans (1 mm voxel and slice spacing) were acquired and 12 C ion beam treatment planning (optimal accelerator energies, beam positions, and particle numbers) for atrioventricular node ablation was conducted. Orthogonal x-rays with matching of 4 implanted clips were used for positioning. Ten Gray treatment plans were repeatedly administered, using pencil beam scanning. After delivery, positron emission tomography-computed tomgraphic scans for detection of β + ( 11 C) activity were obtained. A 12 C beam with a full width at half maximum of 10 mm was delivered to the atrioventricular node. Delivery of 130 Gy caused disturbance of atrioventricular conduction with transition into complete heart block after 160 Gy. Positron emission computed tomgraphy demonstrated dose delivery into the intended area. Application did not induce arrhythmias. Macroscopic inspection did not reveal damage to myocardium. Immunostaining revealed strong γH2AX signals in the target region, whereas no γH2AX signals were detected in the unirradiated control heart. Conclusions— This is the first report of the application of a 12 C beam for ablation of cardiac tissue to treat arrhythmias. Catheter-free ablation using 12C beams is feasible and merits exploration in intact animal studies as an energy source for arrhythmia elimination.

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“…The cardiac radiation effect of blocking electrical conduction had been shown experimentally in porcine and canine models by Guerra et al [12] and Perez-Castellano [13] using beta radiation seeds in a catheter directly applied to cardiac tissue. There is no report of such cardiac therapy using external beam for treatment of arrhythmias.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Radiosurgery (CyberHeart™) for Treatment of Arrhythmia: Physiologic and Histopathologic Correlation in the Porcine Model

Maguire¹,

Gardner²,

Jack³

et al. 2011

Cureus

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Objectives: This porcine pre-clinical investigation sought to demonstrate a new and novel application for radiosurgery, the ablation of cardiac arrhythmias. Pre-clinical studies in the porcine animal model were used to investigate the accuracy with which the pathological region in the heart that is routinely treated for atrial fibrillation could be targeted with radiosurgery. Pathologic and electrophysiologic (EP) changes resulting from radiosurgical ablation were used as primary study endpoints.Methods: Two Hanford mini-swine (approximately 35 kg) were studied. A cardiac-gated CT study was performed. Isocentric treatments were delivered with the CyberKnife® (Accuray Inc, Sunnyvale, CA) in a single fraction at prescribed doses of 25 Gy (N=1) and 35 Gy (N=1). The treatment volume was selected to create electrical isolation of two pulmonary veins (the source of atrial aberrant tachycardias, such as atrial fibrillation) from the body (antrum) of the left atrium, as has been proven successful with thermal catheter ablation procedures. Animals were followed for six months, and then underwent electrophysiologic (EP) testing in the cardiac catheterization lab to test for electrical isolation of the pulmonary veins. Trans esophageal echocardiography was carried out to examine cardiac function post-radiosurgery. Finally, the hearts of the treated animals were submitted for pathologic analysis.

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Pathological Effects of Pulmonary Vein β‐Radiation in a Swine Model

Abstract: Intravascular beta-radiation can induce transmural necrosis and fibrosis of PV myocardial sleeves without PV stenosis and other unwanted effects, which supports a potential usefulness of this energy source in the treatment of AF.

Cited by 12 publications

References 53 publications

Ablation alleviates atrial fibrillation by regulating the signaling pathways of endothelial nitric oxide synthase/nitric oxide via miR‐155‐5p and miR‐24‐3p

Ablation alleviates atrial fibrillation by regulating the signaling pathways of endothelial nitric oxide synthase/nitric oxide via miR‐155‐5p and miR‐24‐3p

Atrioventricular Node Ablation in Langendorff-Perfused Porcine Hearts Using Carbon Ion Particle Therapy

Cardiac Radiosurgery (CyberHeart™) for Treatment of Arrhythmia: Physiologic and Histopathologic Correlation in the Porcine Model

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