Catheter-based renal denervation effectively abolished renal nerve activity initially, but by 11 months post-denervation, functional and anatomical markers returned to normal, indicating reinnervation.
Does catheter-based renal denervation effectively denervate renal nerves and does reinnervation occur in sheep?
Catheter-based renal denervation is initially effective in abolishing renal sympathetic nerve activity, but complete functional and anatomical reinnervation occurs by 11 months in a sheep model.
New Findings What is the topic of this review? Does catheter‐based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur? What advances does it highlight? Following catheter‐based renal denervation, the afferent and efferent responses to electrical stimulation were abolished, renal sympathetic nerve activity was absent, and levels of renal noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin gene‐related peptide were significantly reduced. By 11 months after renal denervation, both the functional responses and anatomical markers of afferent and efferent renal nerves had returned to normal, indicating reinnervation. Renal denervation reduces blood pressure in animals with experimental hypertension and, recently, catheter‐based renal denervation was shown to cause a prolonged decrease in blood pressure in patients with resistant hypertension. The randomized, sham‐controlled Symplicity HTN‐3 trial failed to meet its primary efficacy end‐point, but there is evidence that renal denervation was incomplete in many patients. Currently, there is little information regarding the effectiveness of catheter‐based renal denervation and the extent of reinnervation. We assessed the effectiveness of renal nerve denervation with the Symplicity Flex catheter and the functional and anatomical reinnervation at 5.5 and 11 months postdenervation. In anaesthetized, non‐denervated sheep, there was a high level of renal sympathetic nerve activity, and electrical stimulation of the renal nerve increased blood pressure and reduced heart rate (afferent response) and caused renal vasoconstriction and reduced renal blood flow (efferent response). Immediately after renal denervation, renal sympathetic nerve activity and the responses to electrical stimulation were absent, indicating effective denervation. By 11 months after denervation, renal sympathetic nerve activity was present and the responses to electrical stimulation were normal, indicating reinnervation. Anatomical measures of renal innervation by sympathetic efferent nerves (tissue noradrenaline and tyrosine hydroxylase) and afferent sensory nerves (calcitonin gene‐related peptide) demonstrated large decreases at 1 week postdenervation, but normal levels at 11 months postdenervation. In summary, catheter‐based renal denervation is effective, but reinnervation occurs. Studies of central and renal changes postdenervation are required to understand the causes of the prolonged hypotensive response to catheter‐based renal denervation in human hypertension.
Booth et al. (Thu,) conducted a other in Renal denervation. Catheter-based renal denervation (Symplicity Flex catheter) vs. Pre-denervation baseline was evaluated on Functional and anatomical reinnervation (renal sympathetic nerve activity, responses to electrical stimulation, and anatomical markers). Catheter-based renal denervation effectively abolished renal nerve activity initially, but by 11 months post-denervation, functional and anatomical markers returned to normal, indicating reinnervation.