BACKGROUND: Renal sympathetic hyperactivity is associated with hypertension, a leading cause of mortality worldwide. Renal sympathetic denervation via the Symplicity Catheter System has been shown to decrease blood pressure by 33/11 mmHg by 6 months, with no radiofrequency (RF)-related adverse sequelae visible by CT/MR angiography or renal duplex ultrasound 6 months after the procedure. Here, we present preclinical work predating those clinical results. We performed therapeutic renal sympathetic denervation in a swine animal model to characterize the vascular safety and healing response 6 months after renal denervation therapy. METHODS: In December 2007, seven domestic swine received a total of 32 radiofrequency ablations via the Symplicity Catheter System and were euthanatized 6 months later. Renal angiography was done before, immediately after, and 6 months after procedure. The renal vessels were examined histologically with H&E and Movat pentachrome stains to identify evidence of vascular and neural injury. The kidneys and urinary system were also examined for evidence of gross and microscopic abnormalities. RESULTS: Renal nerve injury involved primarily nerve fibrosis, replacement of nerve fascicles with fibrous connective tissue, and thickening of the epineurium and perineurium. Renal arterial findings included fibrosis of 10-25% of the total media and underlying adventitia, with mild disruption of the external elastic lamina. No significant smooth muscle hyperplasia or inflammatory components were observed. There was no renal arterial stenosis or thrombosis observed by angiography or histology. No gross or microscopic device-related abnormalities were noted in the kidney, surrounding stroma, or urinary bladder. CONCLUSIONS: In a swine model, renal denervation via the Symplicity Catheter System resulted in no clinically significant adverse renal artery or renal findings 6 months after the procedure. This is corroborated by the vascular safety profile demonstrated in subsequent human clinical studies.
BACKGROUND:Renal sympathetic hyperactivity is associated with hypertension, a leading cause of mortality worldwide. Renal sympathetic denervation via the Symplicity Catheter System has been shown to decrease blood pressure by 33/11 mmHg by 6 months, with no radiofrequency (RF)-related adverse sequelae visible by CT/MR angiography or renal duplex ultrasound 6 months after the procedure. Here, we present preclinical work predating those clinical results. We performed therapeutic renal sympathetic denervation in a swine animal model to characterize the vascular safety and healing response 6 months after renal denervation therapy. METHODS: In December 2007, seven domestic swine received a total of 32 radiofrequency ablations via the Symplicity Catheter System and were euthanatized 6 months later. Renal angiography was done before, immediately after, and 6 months after procedure. The renal vessels were examined histologically with H&E and Movat pentachrome stains to identify evidence of vascular and neural injury. The kidneys and urinary system were also examined for evidence of gross and microscopic abnormalities. RESULTS:Renal nerve injury involved primarily nerve fibrosis, replacement of nerve fascicles with fibrous connective tissue, and thickening of the epineurium and perineurium. Renal arterial findings included fibrosis of 10-25% of the total media and underlying adventitia, with mild disruption of the external elastic lamina. No significant smooth muscle hyperplasia or inflammatory components were observed. There was no renal arterial stenosis or thrombosis observed by angiography or histology. No gross or microscopic device-related abnormalities were noted in the kidney, surrounding stroma, or urinary bladder. CONCLUSIONS: In a swine model, renal denervation via the Symplicity Catheter System resulted in no clinically significant adverse renal artery or renal findings 6 months after the procedure. This is corroborated by the vascular safety profile demonstrated in subsequent human clinical studies.
Authors: Véronique L Roger; Alan S Go; Donald M Lloyd-Jones; Robert J Adams; Jarett D Berry; Todd M Brown; Mercedes R Carnethon; Shifan Dai; Giovanni de Simone; Earl S Ford; Caroline S Fox; Heather J Fullerton; Cathleen Gillespie; Kurt J Greenlund; Susan M Hailpern; John A Heit; P Michael Ho; Virginia J Howard; Brett M Kissela; Steven J Kittner; Daniel T Lackland; Judith H Lichtman; Lynda D Lisabeth; Diane M Makuc; Gregory M Marcus; Ariane Marelli; David B Matchar; Mary M McDermott; James B Meigs; Claudia S Moy; Dariush Mozaffarian; Michael E Mussolino; Graham Nichol; Nina P Paynter; Wayne D Rosamond; Paul D Sorlie; Randall S Stafford; Tanya N Turan; Melanie B Turner; Nathan D Wong; Judith Wylie-Rosett Journal: Circulation Date: 2010-12-15 Impact factor: 29.690
Authors: M Esler; G Jennings; P Korner; I Willett; F Dudley; G Hasking; W Anderson; G Lambert Journal: Hypertension Date: 1988-01 Impact factor: 10.190
Authors: Patricia M Kearney; Megan Whelton; Kristi Reynolds; Paul Muntner; Paul K Whelton; Jiang He Journal: Lancet Date: 2005 Jan 15-21 Impact factor: 79.321
Authors: Aram V Chobanian; George L Bakris; Henry R Black; William C Cushman; Lee A Green; Joseph L Izzo; Daniel W Jones; Barry J Materson; Suzanne Oparil; Jackson T Wright; Edward J Roccella Journal: Hypertension Date: 2003-12-01 Impact factor: 10.190
Authors: Katharina Wolf-Maier; Richard S Cooper; Holly Kramer; José R Banegas; Simona Giampaoli; Michel R Joffres; Neil Poulter; Paola Primatesta; Birgitta Stegmayr; Michael Thamm Journal: Hypertension Date: 2003-11-24 Impact factor: 10.190
Authors: Markus P Schlaich; Elisabeth Lambert; David M Kaye; Zygmunt Krozowski; Duncan J Campbell; Gavin Lambert; Jacqui Hastings; Anuradha Aggarwal; Murray D Esler Journal: Hypertension Date: 2003-11-10 Impact factor: 10.190
Authors: Henry Krum; Markus Schlaich; Rob Whitbourn; Paul A Sobotka; Jerzy Sadowski; Krzysztof Bartus; Boguslaw Kapelak; Anthony Walton; Horst Sievert; Suku Thambar; William T Abraham; Murray Esler Journal: Lancet Date: 2009-03-28 Impact factor: 79.321
Authors: Britta Vogel; Michael Kirchberger; Martin Zeier; Felicitas Stoll; Benjamin Meder; Daniel Saure; Martin Andrassy; Oliver J Mueller; Stefan Hardt; Vedat Schwenger; Anna Strothmeyer; Hugo A Katus; Erwin Blessing Journal: Clin Res Cardiol Date: 2013-10-15 Impact factor: 5.460
Authors: Hitesh C Patel; Paramdeep S Dhillon; Felix Mahfoud; Alistair C Lindsay; Carl Hayward; Sabine Ernst; Alexander R Lyon; Stuart D Rosen; Carlo di Mario Journal: Clin Res Cardiol Date: 2014-05 Impact factor: 5.460