Evaluation of renal nerve morphological changes and norepinephrine levels following treatment with novel bipolar radiofrequency delivery systems in a porcine model
OBJECTIVE:To evaluate the safety and effectiveness of different bipolar radiofrequency system algorithms in interrupting the renal sympathetic nerves and reducing renal norepinephrine in a healthy porcine model. METHODS:A porcine model (N = 46) was used to investigate renal norepinephrine levels and...
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Published in: | Journal of hypertension Vol. 32; no. 8; pp. 1678 - 1692 |
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Wolters Kluwer Health | Lippincott Williams & Wilkins
01-08-2014
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Abstract | OBJECTIVE:To evaluate the safety and effectiveness of different bipolar radiofrequency system algorithms in interrupting the renal sympathetic nerves and reducing renal norepinephrine in a healthy porcine model.
METHODS:A porcine model (N = 46) was used to investigate renal norepinephrine levels and changes to renal artery tissues and nerves following percutaneous renal denervation with radiofrequency bipolar electrodes mounted on a balloon catheter. Parameters of the radiofrequency system (i.e. electrode length and energy delivery algorithm), and the effects of single and longitudinal treatments along the artery were studied with a 7-day model in which swine received unilateral radiofrequency treatments. Additional sets of animals were used to examine norepinephrine and histological changes 28 days following bilateral percutaneous radiofrequency treatment or surgical denervation; untreated swine were used for comparison of renal norepinephrine levels.
RESULTS:Seven days postprocedure, norepinephrine concentrations decreased proportionally to electrode length, with 81, 60 and 38% reductions (vs. contralateral control) using 16, 4 and 2-mm electrodes, respectively. Applying a temperature-control algorithm with the 4-mm electrodes increased efficacy, with a mean 89.5% norepinephrine reduction following a 30-s treatment at 68°C. Applying this treatment along the entire artery length affected more nerves vs. a single treatment, resulting in superior norepinephrine reduction 28 days following bilateral treatment.
CONCLUSION:Percutaneous renal artery application of bipolar radiofrequency energy demonstrated safety and resulted in a significant renal norepinephrine content reduction and renal nerve injury compared with untreated controls in porcine models. |
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AbstractList | OBJECTIVETo evaluate the safety and effectiveness of different bipolar radiofrequency system algorithms in interrupting the renal sympathetic nerves and reducing renal norepinephrine in a healthy porcine model. METHODSA porcine model (N = 46) was used to investigate renal norepinephrine levels and changes to renal artery tissues and nerves following percutaneous renal denervation with radiofrequency bipolar electrodes mounted on a balloon catheter. Parameters of the radiofrequency system (i.e. electrode length and energy delivery algorithm), and the effects of single and longitudinal treatments along the artery were studied with a 7-day model in which swine received unilateral radiofrequency treatments. Additional sets of animals were used to examine norepinephrine and histological changes 28 days following bilateral percutaneous radiofrequency treatment or surgical denervation; untreated swine were used for comparison of renal norepinephrine levels. RESULTSSeven days postprocedure, norepinephrine concentrations decreased proportionally to electrode length, with 81, 60 and 38% reductions (vs. contralateral control) using 16, 4 and 2-mm electrodes, respectively. Applying a temperature-control algorithm with the 4-mm electrodes increased efficacy, with a mean 89.5% norepinephrine reduction following a 30-s treatment at 68°C. Applying this treatment along the entire artery length affected more nerves vs. a single treatment, resulting in superior norepinephrine reduction 28 days following bilateral treatment. CONCLUSIONPercutaneous renal artery application of bipolar radiofrequency energy demonstrated safety and resulted in a significant renal norepinephrine content reduction and renal nerve injury compared with untreated controls in porcine models. To evaluate the safety and effectiveness of different bipolar radiofrequency system algorithms in interrupting the renal sympathetic nerves and reducing renal norepinephrine in a healthy porcine model. A porcine model (N = 46) was used to investigate renal norepinephrine levels and changes to renal artery tissues and nerves following percutaneous renal denervation with radiofrequency bipolar electrodes mounted on a balloon catheter. Parameters of the radiofrequency system (i.e. electrode length and energy delivery algorithm), and the effects of single and longitudinal treatments along the artery were studied with a 7-day model in which swine received unilateral radiofrequency treatments. Additional sets of animals were used to examine norepinephrine and histological changes 28 days following bilateral percutaneous radiofrequency treatment or surgical denervation; untreated swine were used for comparison of renal norepinephrine levels. Seven days postprocedure, norepinephrine concentrations decreased proportionally to electrode length, with 81, 60 and 38% reductions (vs. contralateral control) using 16, 4 and 2-mm electrodes, respectively. Applying a temperature-control algorithm with the 4-mm electrodes increased efficacy, with a mean 89.5% norepinephrine reduction following a 30-s treatment at 68°C. Applying this treatment along the entire artery length affected more nerves vs. a single treatment, resulting in superior norepinephrine reduction 28 days following bilateral treatment. Percutaneous renal artery application of bipolar radiofrequency energy demonstrated safety and resulted in a significant renal norepinephrine content reduction and renal nerve injury compared with untreated controls in porcine models. OBJECTIVE:To evaluate the safety and effectiveness of different bipolar radiofrequency system algorithms in interrupting the renal sympathetic nerves and reducing renal norepinephrine in a healthy porcine model. METHODS:A porcine model (N = 46) was used to investigate renal norepinephrine levels and changes to renal artery tissues and nerves following percutaneous renal denervation with radiofrequency bipolar electrodes mounted on a balloon catheter. Parameters of the radiofrequency system (i.e. electrode length and energy delivery algorithm), and the effects of single and longitudinal treatments along the artery were studied with a 7-day model in which swine received unilateral radiofrequency treatments. Additional sets of animals were used to examine norepinephrine and histological changes 28 days following bilateral percutaneous radiofrequency treatment or surgical denervation; untreated swine were used for comparison of renal norepinephrine levels. RESULTS:Seven days postprocedure, norepinephrine concentrations decreased proportionally to electrode length, with 81, 60 and 38% reductions (vs. contralateral control) using 16, 4 and 2-mm electrodes, respectively. Applying a temperature-control algorithm with the 4-mm electrodes increased efficacy, with a mean 89.5% norepinephrine reduction following a 30-s treatment at 68°C. Applying this treatment along the entire artery length affected more nerves vs. a single treatment, resulting in superior norepinephrine reduction 28 days following bilateral treatment. CONCLUSION:Percutaneous renal artery application of bipolar radiofrequency energy demonstrated safety and resulted in a significant renal norepinephrine content reduction and renal nerve injury compared with untreated controls in porcine models. |
Author | Cohen-Mazor, Meital Baird, Rose Zani, Brett G Mathur, Prabodh Mendelsohn, Farrell O Markham, Peter M Stanley, James R.L Rocha-Singh, Krishna Lee, Henry |
AuthorAffiliation | aVessix Vascular and Boston Scientific Corporation, Laguna Hills, California bCBSET Inc., Department of Science Services, Lexington, Massachusetts cCenter for Interventional Hypertension Therapies, Cardiology PC, Birmingham, Alabama dPrairie Heart Institute at St. Johnʼs Hospital, Springfield, Illinois, USA |
AuthorAffiliation_xml | – name: aVessix Vascular and Boston Scientific Corporation, Laguna Hills, California bCBSET Inc., Department of Science Services, Lexington, Massachusetts cCenter for Interventional Hypertension Therapies, Cardiology PC, Birmingham, Alabama dPrairie Heart Institute at St. Johnʼs Hospital, Springfield, Illinois, USA – name: d Prairie Heart Institute at St. John's Hospital, Springfield, Illinois, USA – name: c Center for Interventional Hypertension Therapies, Cardiology PC, Birmingham, Alabama – name: b CBSET Inc., Department of Science Services, Lexington, Massachusetts – name: a Vessix Vascular and Boston Scientific Corporation, Laguna Hills, California |
Author_xml | – sequence: 1 givenname: Meital surname: Cohen-Mazor fullname: Cohen-Mazor, Meital organization: aVessix Vascular and Boston Scientific Corporation, Laguna Hills, California bCBSET Inc., Department of Science Services, Lexington, Massachusetts cCenter for Interventional Hypertension Therapies, Cardiology PC, Birmingham, Alabama dPrairie Heart Institute at St. Johnʼs Hospital, Springfield, Illinois, USA – sequence: 2 givenname: Prabodh surname: Mathur fullname: Mathur, Prabodh – sequence: 3 givenname: James surname: Stanley middlename: R.L fullname: Stanley, James R.L – sequence: 4 givenname: Farrell surname: Mendelsohn middlename: O fullname: Mendelsohn, Farrell O – sequence: 5 givenname: Henry surname: Lee fullname: Lee, Henry – sequence: 6 givenname: Rose surname: Baird fullname: Baird, Rose – sequence: 7 givenname: Brett surname: Zani middlename: G fullname: Zani, Brett G – sequence: 8 givenname: Peter surname: Markham middlename: M fullname: Markham, Peter M – sequence: 9 givenname: Krishna surname: Rocha-Singh fullname: Rocha-Singh, Krishna |
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Cites_doi | 10.1152/physrev.1997.77.1.75 10.1016/S0140-6736(09)60566-3 10.1016/S0895-7061(00)00225-9 10.1161/01.HYP.5.1.86 10.1016/j.jacc.2013.08.1616 10.1046/j.1440-1681.2001.03566.x 10.1002/ca.21280 10.1161/HYPERTENSIONAHA.109.138610 10.1016/j.amjhyper.2003.10.010 10.1007/s00392-011-0346-8 10.1016/j.aca.2010.04.051 10.1097/HJH.0b013e32835821e5 10.1161/01.HYP.0000103160.35395.9E |
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References_xml | – volume: 77 start-page: 75 year: 1997 ident: R7-20-20210208 article-title: Neural control of renal function. publication-title: Physiol Rev doi: 10.1152/physrev.1997.77.1.75 contributor: fullname: DiBona – volume: 247 start-page: F50 year: 1984 ident: R3-20-20210208 article-title: Innervation of the renal cortical tubules: a quantitative study. publication-title: Am J Physiol contributor: fullname: Barajas – volume: 373 start-page: 1275 year: 2009 ident: R14-20-20210208 article-title: Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. publication-title: Lancet doi: 10.1016/S0140-6736(09)60566-3 contributor: fullname: Krum – volume: 13 start-page: 99S year: 2000 ident: R4-20-20210208 article-title: The sympathetic system and hypertension. publication-title: Am J Hypertens doi: 10.1016/S0895-7061(00)00225-9 contributor: fullname: Esler – volume: 5 start-page: 86 year: 1983 ident: R2-20-20210208 article-title: Plasma catecholamines and essential hypertension. An analytical review. publication-title: Hypertension doi: 10.1161/01.HYP.5.1.86 contributor: fullname: Goldstein – volume: 62 start-page: 2031 year: 2013 ident: R15-20-20210208 article-title: International Expert Consensus Statement: percutaneous transluminal renal denervation for the treatment of resistant hypertension. publication-title: J Am Coll Cardiol doi: 10.1016/j.jacc.2013.08.1616 contributor: fullname: Schlaich – volume: 28 start-page: 986 year: 2001 ident: R5-20-20210208 article-title: Sympathetic nerve biology in essential hypertension. publication-title: Clin Exp Pharmacol Physiol doi: 10.1046/j.1440-1681.2001.03566.x contributor: fullname: Esler – volume: 25 start-page: 628 year: 2012 ident: R8-20-20210208 article-title: Micro-anatomy of the renal sympathetic nervous system: a human postmortem histologic study. publication-title: Clin Anat doi: 10.1002/ca.21280 contributor: fullname: Atherton – volume: 54 start-page: 1195 year: 2009 ident: R1-20-20210208 article-title: Renal denervation as a therapeutic approach for hypertension: novel implications for an old concept. publication-title: Hypertension doi: 10.1161/HYPERTENSIONAHA.109.138610 contributor: fullname: Schlaich – volume: 17 start-page: 217 year: 2004 ident: R6-20-20210208 article-title: Relationship between central sympathetic activity and stages of human hypertension. publication-title: Am J Hypertens doi: 10.1016/j.amjhyper.2003.10.010 contributor: fullname: Smith – volume: 100 start-page: 1095 year: 2011 ident: R9-20-20210208 article-title: Catheter-based renal sympathetic denervation: chronic preclinical evidence for renal artery safety. publication-title: Clin Res Cardiol doi: 10.1007/s00392-011-0346-8 contributor: fullname: Rippy – volume: 670 start-page: 84 year: 2010 ident: R11-20-20210208 article-title: Simultaneous determination of plasma epinephrine and norepinephrine using an integrated strategy of a fully automated protein precipitation technique, reductive ethylation labeling and UPLC-MSMS. publication-title: Anal Chim Acta doi: 10.1016/j.aca.2010.04.051 contributor: fullname: Ji – volume: 30 start-page: 2230 year: 2012 ident: R12-20-20210208 article-title: Morphological assessment of renal arteries after radiofrequency catheter-based sympathetic denervation in a porcine model. publication-title: J Hypertens doi: 10.1097/HJH.0b013e32835821e5 contributor: fullname: Steigerwald – volume: 43 start-page: 169 year: 2004 ident: R13-20-20210208 article-title: Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and angiotensin neuromodulation. publication-title: Hypertension doi: 10.1161/01.HYP.0000103160.35395.9E contributor: fullname: Schlaich |
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SubjectTerms | Animals Blood Pressure Catheter Ablation - methods Creatinine - blood Heart Rate Kidney - chemistry Kidney - innervation Models, Animal Norepinephrine - analysis ORIGINAL PAPERS: Therapeutic aspects Renal Artery - innervation Renal Artery - pathology Swine Sympathectomy - methods Tyrosine 3-Monooxygenase - analysis |
Title | Evaluation of renal nerve morphological changes and norepinephrine levels following treatment with novel bipolar radiofrequency delivery systems in a porcine model |
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