A non-vascular treatment for resistant hypertension: preclinical and first in man experience

Abstract

Purpose: Studies show that renal denervation or the interruption of renal afferent nerve activity attenuates systemic sympathetic tone, thereby lowering blood pressure. The natural orifice denervation system developed by Verve Medical directs radiofrequency energy to the renal pelvis where the preponderance of afferent nerves are located and closely accessible. We present our early porcine studies looking at both histopathology of nerve ablation as well as levels of nore-pinephrine in the acute and chronic model. Method: Eight female domestic swine weighing 60-65kg underwent renal pelvic denervation via ureteral access. Three were euthanized immediately after delivery of RF energy; five animals were survived for 7 days. Renal cortical nore-pinephrine levels were measured in both groups of animals. We also assessed histopathology in the treated zone for confirmation of nerve damage. The animals were sedated with Ketamine, intubated, and maintained on isoflu-rane anesthesia throughout the procedure. A ventral midline laparotomy was performed to expose the urinary bladder. A 5cm incision was made in the ventral aspect of the bladder to access the ureteral orifice. The VERVE device was passed retrograde over a 0.035'' guidewire from the bladder to the renal pelvis and RF performed. The procedure was repeated in the contralateral kidney. In 2 animals, RF energy was not applied to the contralateral kidney (sham procedure). The urinary bladder and laparotomy were closed and the animal was recovered from anesthesia. Animals were survived for 7 days. In 2 animals, bilateral pyelogram, ureterogram, and renal angiography was performed prior to euthanasia with KCl under general anesthesia. Immediately following euthanasia renal cortical tissue was harvested for determination of tissue norepinephrine concentration by HPLC. The kidneys were then perfusion fixed and harvested for histopathologic analysis. Result: Follow-up pyelography, ureterography, and renal arterial angiography were performed in 2 animals and were unremarkable. In all animals there was a reduction of norepinephrine levels compared to control samples. Reduction of tissue norepinephrine concentration ranged from 11% to 89% with a mean reduction of 61%. Histopathology confirmed nerve ablation. Conclusion: In this small series of acute and chronic animals, we see a promising non-vascular alternative for renal denervation. The catheter introduction requires little skill with no damage to surrounding tissue and can be performed without systematic contrast utilization. The first in man experience will be available at the time of the presentation.