Use of the Peregrine Catheter Infusion System to develop novel targeted renal nerve ablation therapies in hypertensive sheep

Abstract

Background and Objective: Clinical trials have shown that catheter-based total (efferent and afferent) renal denervation (TRDN) can effectively lower arterial pressure in patients with treatment-resistant hypertension (HTN). The Peregrine catheter infusion system deploys microneedles from the renal artery lumen into the renal artery adventitia to inject the neurolytic agent ethanol. The objective of this study was to utilize this catheter to develop novel renal denervation therapies in a large animal model. In this study our aim was to demonstrate that TRDN lowers arterial pressure in the deoxycorticosterone acetate and high salt diet (DOCA-salt) sheep model of HTN. This will establish the utility of this catheter to deliver the afferent nerve neurolytic agent, capsaicin. Our group has shown that selective afferent renal denervation (ARDN) lowers arterial pressure to the same degree as TRDN in DOCA-salt HTN rats. Our long-term goal is to translate these findings to the DOCA-salt sheep model and eventually humans. Methods: Adult Domestic sheep weighing 60-80 kg were implanted with a subcutaneous silicone pellet containing DOCA (350mg/kg) and given access to salted (0.2% NaCl) drinking water and (180mEq Na+/kg) feed. Stellar radio telemeters were implanted for continuous measurement of MAP. 30 days following induction of DOCA-salt HTN, the Peregrine catheter infusion system was used to perform bilateral TRDN. One month after TRDN, animals were terminated and kidneys were harvested to verify denervation efficacy. Preliminary Results: 30 days following implantation of DOCA, 24hr MAP increased ~25mmHg from a baseline of 99mmHg to 123mmHg (n=2). 30 days following TRDN, 24hr MAP decreased to near control levels of 105mmHg. Conclusion and Future Directions: These preliminary results demonstrate that TRDN with the Peregrine catheter lowers MAP in DOCA-salt HTN sheep. The mechanism underlying this response is still being investigated. Sheep studies are underway to utilize the Peregrine catheter to perform ARDN by injection of capsaicin into the renal artery adventitia. The goal is to conduct a translational study to move catheter-based ARDN into clinical trials. If catheter-based ARDN lowers MAP to the same degree as TRDN, efferent renal nerves could be preserved to maintain MAP and blood volume in response to hemorrhagic or septic shock. Supported by NHLBI R01 HL116476. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.