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Catheter-based renal sympathetic denervation: chronic preclinical evidence for renal artery safety

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Abstract

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.

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References

  1. Wolf-Maier K, Cooper RS, Kramer H, Banegas JR, Giampaoli S, Joffres MR, Poulter N, Primatesta P, Stegmayr B, Thamm M (2004) Hypertension treatment and control in five European countries, Canada, and the United States. Hypertension 43(1):10–17. doi:10.1161/01.HYP.0000103630.72812.10

    Article  PubMed  CAS  Google Scholar 

  2. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360(9349):1903–1913 (pii:S0140673602119118)

    Article  PubMed  Google Scholar 

  3. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42(6):1206–1252. doi:10.1161/01.HYP.0000107251.49515.c2

    Article  PubMed  CAS  Google Scholar 

  4. World Health Organization (WHO) (2009) Global health risks: mortality and burden of disease attributable to selected major risks

  5. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365(9455):217–223. doi:10.1016/S0140-6736(05)17741-1

    PubMed  Google Scholar 

  6. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J (2011) Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation 123(4):e18–e209. doi:10.1161/CIR.0b013e3182009701

    Article  PubMed  Google Scholar 

  7. Erdine S (2010) Compliance with the treatment of hypertension: the potential of combination therapy. J Clin Hypertens (Greenwich) 12(1):40–46. doi:10.1111/j.1751-7176.2009.00200.x

    Article  CAS  Google Scholar 

  8. Fergus IV (2009) Antihypertensive pharmacotherapy: adverse effects of medications promote nonadherence. J Cardiometab Syndr 4(1):E1–E3. doi:10.1111/j.1559-4572.2008.00053.x

    Article  PubMed  Google Scholar 

  9. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M (2010) Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 376(9756):1903–1909. doi:10.1016/S0140-6736(10)62039-9

    Article  PubMed  Google Scholar 

  10. Di Bona GF (2002) Sympathetic nervous system and the kidney in hypertension. Curr Opin Nephrol Hypertens 11(2):197–200

    Article  Google Scholar 

  11. Di Bona GF, Kopp UC (1997) Neural control of renal function. Physiol Rev 77(1):75–197

    Google Scholar 

  12. Esler M, Jennings G, Korner P, Willett I, Dudley F, Hasking G, Anderson W, Lambert G (1988) Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension 11(1):3–20

    PubMed  CAS  Google Scholar 

  13. Schlaich MP, Lambert E, Kaye DM, Krozowski Z, Campbell DJ, Lambert G, Hastings J, Aggarwal A, Esler MD (2004) Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and Angiotensin neuromodulation. Hypertension 43(2):169–175. doi:10.1161/01.HYP.0000103160.35395.9E01

    Article  PubMed  CAS  Google Scholar 

  14. DiBona GF, Esler M (2010) Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol 298(2):R245–R253. doi:10.1152/ajpregu.00647.2009

    Article  PubMed  CAS  Google Scholar 

  15. Esler M (2010) The 2009 Carl Ludwig Lecture: pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management. J Appl Physiol 108(2):227–237. doi:10.1152/japplphysiol.00832.2009

    Article  PubMed  CAS  Google Scholar 

  16. Symplicity HTN-1 Investigators (2011) Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension 57(5):911–917. doi:10.1161/HYPERTENSIONAHA.110.163014

    Article  Google Scholar 

  17. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M (2009) Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 373(9671):1275–1281. doi:10.1016/S0140-6736(09)60566-3

    Article  PubMed  Google Scholar 

  18. Esler M, Schlaich M, Sobotka P, Whitbourn R, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham W, Krum H (2009) Catheter-based renal denervation reduces total body and renal noradrenaline spillover and blood pressure in resistant hypertension. J Hypertens 27(suppl 4):s167

    Google Scholar 

  19. Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, Hoppe UC, Vonend O, Rump LC, Sobotka PA, Krum H, Esler M, Bohm M (2011) Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation 123(18):1940–1946. doi:10.1161/CIRCULATIONAHA.110.991869

    Article  PubMed  CAS  Google Scholar 

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Conflict of Interest

Authors MKR, KLD, and CKZ are independent consultants paid for their time. Authors DZ, NCB, and AW are employees and stockholders of Medtronic Ardian.

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Correspondence to Marian K. Rippy.

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Rippy, M.K., Zarins, D., Barman, N.C. et al. Catheter-based renal sympathetic denervation: chronic preclinical evidence for renal artery safety. Clin Res Cardiol 100, 1095–1101 (2011). https://doi.org/10.1007/s00392-011-0346-8

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  • DOI: https://doi.org/10.1007/s00392-011-0346-8

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