Early Changes in Rat Heart After High‐Dose Irradiation: Implications for Antiarrhythmic Effects of Cardiac Radioablation

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Noninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early‐period antiarrhythmic effects induced by high‐dose irradiation are unknown. This study investigated dose‐responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart.

Methods and Results

Whole hearts of wild‐type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks’ postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high‐dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose‐responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion.

Conclusions

Mononuclear cell–related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high‐dose irradiation. ECG indicated intracardiac conduction delay with prominent ST‐segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.

Related collections

Most cited references 40

Record: found
Abstract: found
Article: not found

Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia

Phillip S Cuculich, Clifford Robinson, Yoram Rudy … (2017)

BACKGROUND Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT). We combined these techniques to perform catheter-free, electrophysiology-guided, noninvasive cardiac radioablation for ventricular tachycardia. METHODS We targeted arrhythmogenic scar regions by combining anatomical imaging with noninvasive electrocardiographic imaging during ventricular tachycardia that was induced by means of an implantable cardioverter–defibrillator (ICD). SBRT simulation, planning, and treatments were performed with the use of standard techniques. Patients were treated with a single fraction of 25 Gy while awake. Efficacy was assessed by counting episodes of ventricular tachycardia, as recorded by ICDs. Safety was assessed by means of serial cardiac and thoracic imaging. RESULTS From April through November 2015, five patients with high-risk, refractory ventricular tachycardia underwent treatment. The mean noninvasive ablation time was 14 minutes (range, 11 to 18). During the 3 months before treatment, the patients had a combined history of 6577 episodes of ventricular tachycardia. During a 6-week postablation “blanking period” (when arrhythmias may occur owing to postablation inflammation), there were 680 episodes of ventricular tachycardia. After the 6-week blanking period, there were 4 episodes of ventricular tachycardia over the next 46 patient-months, for a reduction from baseline of 99.9%. A reduction in episodes of ventricular tachycardia occurred in all five patients. The mean left ventricular ejection fraction did not decrease with treatment. At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year. CONCLUSIONS In five patients with refractory ventricular tachycardia, noninvasive treatment with electrophysiology-guided cardiac radioablation markedly reduced the burden of ventricular tachycardia. (Funded by Barnes–Jewish Hospital Foundation and others.)

0 comments Cited 168 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia

Clifford Robinson, Pamela Samson, Kaitlin M.S. Moore … (2019)

Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy (SBRT), though prospective data is lacking. We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electrical cardiac imaging with a standard SBRT workflow followed by delivery of a single fraction of 25 Gray (Gy) to the target. The primary safety endpoint was treatment-related serious adverse events (SAE) in the first 90 days. The primary efficacy endpoint was any reduction in VT episodes (tracked by indwelling ICDs) or any reduction in PVC burden (as measured by 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6 week blanking window after treatment). Health-related quality of life was assessed using the Short Form (SF-36) questionnaire. Nineteen patients were enrolled (17 for VT, 2 for PVC-cardiomyopathy). Median noninvasive ablation time was 15.3 minutes (range, 5.4–32.3). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related SAE. Median number of VT episodes was reduced from 119 (range 4–292) to 3 (range 0–31, p < 0.001). Reduction was observed for both ICD shocks and anti-tachycardia pacing. VT episodes or PVC burden were reduced in 17/18 evaluable patients (94%). The frequency of VT episodes or PVC burden was reduced by 75% in 89% of patients. Overall survival was 89% at 6 months and 72% at 12 months. Use of dual antiarrhythmic medications decreased from 59% to 12% (p=0.008). Quality of life improved in 5 of 9 SF-36 domains at 6 months. Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life. URL: https://clinicaltrials.gov . Unique identifiers: NCT02919618

0 comments Cited 128 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Radiation-induced fibrosis: mechanisms and implications for therapy.

Jeffrey M Straub, Jacob New, Chase D Hamilton … (2015)

Radiation-induced fibrosis (RIF) is a long-term side effect of external beam radiation therapy for the treatment of cancer. It results in a multitude of symptoms that significantly impact quality of life. Understanding the mechanisms of RIF-induced changes is essential to developing effective strategies to prevent long-term disability and discomfort following radiation therapy. In this review, we describe the current understanding of the etiology, clinical presentation, pathogenesis, treatment, and directions of future therapy for this condition. A literature review of publications describing mechanisms or treatments of RIF was performed. Specific databases utilized included PubMed and clinicaltrials.gov, using keywords "Radiation-Induced Fibrosis," "Radiotherapy Complications," "Fibrosis Therapy," and other closely related terms. RIF is the result of a misguided wound healing response. In addition to causing direct DNA damage, ionizing radiation generates reactive oxygen and nitrogen species that lead to localized inflammation. This inflammatory process ultimately evolves into a fibrotic one characterized by increased collagen deposition, poor vascularity, and scarring. Tumor growth factor beta serves as the primary mediator in this response along with a host of other cytokines and growth factors. Current therapies have largely been directed toward these molecular targets and their associated signaling pathways. Although RIF is widely prevalent among patients undergoing radiation therapy and significantly impacts quality of life, there is still much to learn about its pathogenesis and mechanisms. Current treatments have stemmed from this understanding, and it is anticipated that further elucidation will be essential for the development of more effective therapies.

0 comments Cited 124 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Seil Oh:

ORCID: https://orcid.org/0000-0002-2504-9615

seil@snu.ac.kr

Ji Hyun Chang:

ORCID: https://orcid.org/0000-0001-5921-5522

jh.chang@snu.ac.kr

Journal

Journal ID (nlm-ta): J Am Heart Assoc

Journal ID (iso-abbrev): J Am Heart Assoc

Journal ID (doi): 10.1002/(ISSN)2047-9980

Journal ID (publisher-id): JAH3

Journal ID (hwp): ahaoa

Title: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2047-9980

Publication date (Electronic): 04 March 2021

Publication date Collection: 16 March 2021

Volume: 10

Issue: 6 ( doiID: 10.1002/jah3.v10.6 )

Electronic Location Identifier: e019072

Affiliations

[ ¹ ] Division of Cardiology Department of Internal Medicine Seoul National University Hospital Seoul South Korea

[ ² ] Departments of Pathology Seoul National University Hospital Seoul South Korea

[ ³ ] Department of Radiation Oncology Seoul National University College of Medicine Seoul Korea

[ ⁴ ] Department of Radiation Oncology Seoul National University Hospital Seoul South Korea

[ ⁵ ] Cancer Research Institute Seoul National University College of Medicine Seoul Korea

[ ⁶ ] Seoul National University College of Medicine Seoul Korea

Author notes

[*] [* ] Correspondence to: Ji Hyun Chang, MD, PhD, Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak‐ro, Jongno‐gu, Seoul 03080, Korea. E‐mail: jh.chang@ 123456snu.ac.kr

and

Seil Oh, MD, PhD, FESC, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak‐ro, Jongno‐gu, Seoul 03080, Korea. E‐mail: seil@ 123456snu.ac.kr

[*]

Professor Oh and Professor Chang contributed equally to this work.

Author information

Myung‐Jin Cha https://orcid.org/0000-0001-6180-0157

Jeong‐Wook Seo https://orcid.org/0000-0003-0242-1805

Seil Oh https://orcid.org/0000-0002-2504-9615

Ji Hyun Chang https://orcid.org/0000-0001-5921-5522

Article

Publisher ID: JAH35988

DOI: 10.1161/JAHA.120.019072

PMC ID: 8174197

PubMed ID: 33660526

SO-VID: b0eaeb44-aa66-488a-9731-af63cf0b6059

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

History

Date received : 19 October 2020

Date accepted : 14 January 2021

Page count

Figures: 6, Tables: 0, Pages: 11, Words: 5821

Funding

Funded by: National Research Foundation of Korea , open-funder-registry 10.13039/501100003725;

Award ID: NRF‐2018M2A2B3A01070410

Award ID: NRF‐2020R1A2C1013832

Funded by: Ministry of Science & Information Communication Technology

Custom metadata

source-schema-version-number 2.0

cover-date March 16, 2021

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.1 mode:remove_FC converted:09.04.2021

ScienceOpen disciplines: Cardiovascular Medicine

Keywords: antiarrhythmic effect,cardiac radioablation,radiation,rats,ventricular arrhythmia,animal models of human disease,mechanisms,pathophysiology

Data availability:

ScienceOpen disciplines: Cardiovascular Medicine

Keywords: antiarrhythmic effect, cardiac radioablation, radiation, rats, ventricular arrhythmia, animal models of human disease, mechanisms, pathophysiology

Early Changes in Rat Heart After High‐Dose Irradiation: Implications for Antiarrhythmic Effects of Cardiac Radioablation

Read this article at

Abstract

Background

Methods and Results

Conclusions

Related collections

Cardiovascular Innovations and Applications

Most cited references 40

Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia

Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia

Radiation-induced fibrosis: mechanisms and implications for therapy.

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Page count

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 258

Cited by 14

Most referenced authors 388