Early Morphologic Alterations in Renal Artery Wall and Renal Nerves in Response to Catheter-Based Renal Denervation Procedure in Sheep: Difference Between Single-Point and Multiple-Point Ablation Catheters

Abstract

Renal sympathetic hyperactivity is critically involved in hypertension pathophysiology; renal denervation (RDN) presents a novel strategy for treatment of resistant hypertension cases. This study assessed effects of two RDN systems to detect acute intravascular, vascular and peri-vascular changes in the renal artery, and renal nerve alterations, in the sheep. The procedures using a single-point or multi-point ablation catheters, Symplicity FlexTM, Medtronic versus EnligHTNTM, St. Jude Medical were compared; the intact contralateral kidneys served as controls. Histopathological and immunohistochemical assessments were performed 48 h after RDN procedures; the kidney and suprarenal gland morphology was also evaluated. Special staining methods were applied for histologic analysis, to adequately score the injury of renal artery and adjacent renal nerves. These were more pronounced in the animals treated with the multi-point compared with the single-point catheter. However, neither RDN procedure led to complete renal nerve ablation. Forty-eight hours after the procedure no significant changes in plasma and renal tissue catecholamines were detected. The morphologic changes elicited by application of both RDN systems appeared to be dependent on individual anatomical variability of renal nerves in the sheep. Similar variability in humans may limit the therapeutic effectiveness of RDN procedures used in patients with resistant hypertension.

Evaluation of Later Morphologic Alterations in Renal Artery Wall and Renal Nerves in Response to Catheter-Based Renal Denervation in Sheep: Comparison of the Single-Point and Multiple-Point Ablation Catheters

“…To follow our previous study (Táborský et al 2017), the animals were randomly assigned into two mixed sex groups (n=6 in each group). All intervention procedures were designed as described recently (Táborský et al 2017): anesthesia was induced with combination of propofol (10 mg/kg; Fresenius Kabi, Bad Homburg, Germany) and fentanyl (3 mg/kg; Torrex, Chiesi, Wien, Austria) given intravenously. After endotracheal intubation, anesthesia was maintained with 0.5 % to 2.0 % isoflurane (Isofluran Rhodia, Nicholas Piramar, Mumbai, India) -O 2 /air mixture.…”

“…(Torbugesic, Zoetis Manufacturing and Research Spain S.L., Vall de Bianya, Spain) was administered. 10 days post-RDN the animals were anesthetized and prepared by the same procedure as described above for the second angiography of both renal arteries via left femoral artery (Táborský et al 2017). After that, the animals were euthanized by an anesthetics overdose (thiopental, VUAB Brno, Czech Republic) with KCl.…”

“…Therefore, Vol. 67 experimental approaches are still important to reveal direct morphologic alterations in the renal artery and renal nerves in response to catheter-based RDN (Rippy et al 2011, Steigerwald et al 2012, Cohen-Mazor et al 2014, Sakakura et al 2015, Táborský et al 2017.…”

“…In our previous study (Táborský et al 2017), we elucidated single-point and multi-point RDN-induced early changes in sheep as vascular and nerve injury score along the renal artery 48 h post procedure. Although the multi-point system displayed significantly higher efficiency in comparison with single-point device, we determined that neither of the RDN systems achieved complete damage of the targeted renal nerve plexus or significantly reduced the level of catecholamines in the post-RDN kidney.…”

“…Histopathology and immunohistochemistry evaluation was also performed to describe present alterations to the affected renal artery and accompanying renal nerve plexus in comparison with the contralateral renal artery. We focused on the description of radio-frequency ablation induced subacute intravascular, vascular and peri-vascular changes by single-point and multiple-point ablation catheters as we reported previously (Táborský et al 2017).…”