Renal denervation by CT-guided periarterial injection of hyperosmolar saline, vincristine, paclitaxel and guanethidine in a pig model

EuroIntervention. 2017 Apr 7;12(18):e2262-e2270. doi: 10.4244/EIJ-D-15-00354.

Abstract

Aims: The aim of the study was to evaluate the feasibility, safety and efficacy of renal sympathetic denervation with CT-guided periarterial injection of potentially neurolytic agents in pigs.

Methods and results: Unilateral injection of formulations containing either 5M hyperosmolar saline, vincristine, paclitaxel or guanethidine around the renal artery was performed in 24 normotensive pigs with six animals per group. Needle placement and injections were performed under CT fluoroscopy guidance. Blood pressure measurements and CT scans were performed immediately before and after the intervention and four weeks after treatment. After euthanasia, norepinephrine (NE) concentrations of both kidneys were determined. The renal arteries and surrounding tissue were examined histologically to evaluate nerve fibre degeneration. Procedures were technically successful with good periarterial distribution of the injectant in all but one pig in the guanethidine group. No major adverse events or post-interventional complications occurred. In the vincristine group, NE concentrations of the renal parenchyma were lower on the treated side in all pigs with a mean decrease of 53% (38%-62%, p<0.01) compared to the contralateral control. Correspondingly, histological examination revealed neural degeneration in all animals treated with vincristine. In the other groups, no significant drop of NE values, or histological signs of nerve fibre degeneration were found.

Conclusions: CT-guided periarterial injection of the different substances was feasible and safe. Renal sympathetic denervation was achieved with vincristine. In contrast, hyperosmolar saline, paclitaxel and guanethidine do not seem to be appropriate for renal denervation in a pig model at the dosage used.

MeSH terms

  • Animals
  • Blood Pressure
  • Guanethidine / administration & dosage*
  • Kidney / chemistry
  • Kidney / diagnostic imaging
  • Kidney / innervation*
  • Kidney / pathology
  • Norepinephrine / analysis
  • Paclitaxel / administration & dosage*
  • Swine
  • Sympathectomy / methods*
  • Tomography, X-Ray Computed / methods*
  • Vincristine / administration & dosage*

Substances

  • Vincristine
  • Paclitaxel
  • Norepinephrine
  • Guanethidine