Interventions for hypertension and stroke

Translational value of preclinical models for renal denervation: a histological comparison of human versus porcine renal nerve anatomy

EuroIntervention 2023;18:e1120-e1128. DOI: 10.4244/EIJ-D-22-00369

Yu Sato
Yu Sato1, MD; Andrew S.P. Sharp2, MD; Felix Mahfoud3, MD; Stefan Tunev4, DVM; Ashley Forster1, BS; Matthew Ellis1, BS; Ana Gomez1; Roma Dhingra1; Jeremy Ullman1; Markus Schlaich5, MD; David Lee6, MD; Julie Trudel4, PhD; Douglas A. Hettrick4, PhD; David E. Kandzari7, MD; Renu Virmani1, MD; Aloke V. Finn1,8, MD
1. CVPath Institute Inc., Gaithersburg, MD, USA; 2. University Hospital of Wales, Cardiff, UK; 3. Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Hospital, Hamburg, Germany; 4. Medtronic, Santa Rosa, CA, USA; 5. University of Western Australia, Perth, Australia; 6. Stanford Hospital and Clinics, Palo Alto, CA, USA; 7. Department of Cardiovascular Surgery, Marcus Valve Center, Piedmont Heart Institute, Atlanta, GA, USA; 8. University of Maryland, Baltimore, MD, USA

Background: Preclinical models have provided key insights into the response of local tissues to radiofrequency (RF) renal denervation (RDN) that is unobtainable from human studies. However, the anatomic translatability of these models to the procedure in humans is incompletely understood. 

Aims: We aimed to compare the renal arterial anatomy in normotensive pigs treated with RF-RDN to that of human cadavers to evaluate the suitability of normotensive pigs for determining the safety of RF-RDN.

Methods: Histopathologic analyses were performed on RF-treated renal arteries in a porcine model and untreated control renal arteries. Similar analyses were performed on untreated renal arteries from human cadavers. 

Results: In both human and porcine renal arteries, the median number of nerves was lower in the more distal sections (the numbers in the proximal, middle, distal, 1st bifurcation, and 2nd bifurcation sections were 65, 58, 47, 22.5, and 14.7 in humans, respectively, and 39, 26, 29, 16.5, and 9.3 in the porcine models, respectively). Renal nerves were common in the regions between arteries and adjacent veins, but only 3% and 13% of the renal nerves in humans and pigs, respectively, were located behind the renal vein. The semiquantitative score of RF-induced renal arterial nerve necrosis was significantly greater at 7 days than 28 days (0.98 vs 0.75; p=0.01), and injury to surrounding organs was rarely observed.

Conclusions: The distribution of nerve tissue and the relative distribution of extravascular anatomic structures along the renal artery was similar between humans and pigs, which validates the translational value of the normotensive porcine model for RDN. 

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