Reetu R Singh1, Varsha Sajeesh2, Lindsea C Booth3, Zoe McArdle2, Clive N May3, Geoffrey A Head4, Karen M Moritz5, Markus P Schlaich6, Kate M Denton2. 1. Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, Australia. Electronic address: reetu.singh@monash.edu. 2. Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, Australia. 3. The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia. 4. Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia. 5. School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia. 6. Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia.
Abstract
BACKGROUND: Clinical trials applying catheter-based radiofrequency renal denervation (RDN) demonstrated a favorable safety profile with minimal acute or procedural adverse events. Whether ablation of renal nerves adversely affects compensatory responses to hemodynamic challenge has not been extensively investigated. OBJECTIVES: The aim of this study was to examine the effect of RDN on mean arterial pressure, renal function, and the reflex response to hemorrhage in sheep with normotension (control) or with hypertensive chronic kidney disease (CKD). METHODS: Sheep underwent RDN (control-RDN, n = 8; CKD-RDN, n = 7) or sham procedures (control-intact, n = 6; CKD-intact, n = 7). Response to hemorrhage (20% loss of blood volume), including plasma renin activity, was assessed at 2 and 5 months post-procedure. RESULTS: RDN caused a complete reversal of hypertension and improved renal function in CKD-RDN sheep (p < 0.0001 for 2 and 5 months vs. pre-RDN). In response to hemorrhage, mean arterial pressure fell in all groups, with the fall being greater in the RDN than the intact group (2-month fall in mean arterial pressure: control-intact, -10 ± 1 mm Hg; control-RDN, -15 ± 1 mm Hg; p < 0.05; CKD-intact, -11 ± 3 mm Hg; CKD-RDN, -19 ± 9 mm Hg; p < 0.001). Hemorrhage increased heart rate and plasma renin activity in intact sheep, but these responses were significantly attenuated in control-RDN and CKD-RDN animals. Responses to hemorrhage were remarkably similar at 2 and 5 months post-RDN, which suggests that nerve function had not returned within this time frame. CONCLUSIONS: In hypertensive CKD sheep, RDN reduced blood pressure and improved basal renal function but markedly compromised compensatory hemodynamic responses to hemorrhage. Therefore, the capacity to respond to a physiological challenge to body fluid homeostasis may be compromised following RDN.
BACKGROUND: Clinical trials applying catheter-based radiofrequency renal denervation (RDN) demonstrated a favorable safety profile with minimal acute or procedural adverse events. Whether ablation of renal nerves adversely affects compensatory responses to hemodynamic challenge has not been extensively investigated. OBJECTIVES: The aim of this study was to examine the effect of RDN on mean arterial pressure, renal function, and the reflex response to hemorrhage in sheep with normotension (control) or with hypertensive chronic kidney disease (CKD). METHODS:Sheep underwent RDN (control-RDN, n = 8; CKD-RDN, n = 7) or sham procedures (control-intact, n = 6; CKD-intact, n = 7). Response to hemorrhage (20% loss of blood volume), including plasma renin activity, was assessed at 2 and 5 months post-procedure. RESULTS: RDN caused a complete reversal of hypertension and improved renal function in CKD-RDN sheep (p < 0.0001 for 2 and 5 months vs. pre-RDN). In response to hemorrhage, mean arterial pressure fell in all groups, with the fall being greater in the RDN than the intact group (2-month fall in mean arterial pressure: control-intact, -10 ± 1 mm Hg; control-RDN, -15 ± 1 mm Hg; p < 0.05; CKD-intact, -11 ± 3 mm Hg; CKD-RDN, -19 ± 9 mm Hg; p < 0.001). Hemorrhage increased heart rate and plasma renin activity in intact sheep, but these responses were significantly attenuated in control-RDN and CKD-RDN animals. Responses to hemorrhage were remarkably similar at 2 and 5 months post-RDN, which suggests that nerve function had not returned within this time frame. CONCLUSIONS: In hypertensive CKD sheep, RDN reduced blood pressure and improved basal renal function but markedly compromised compensatory hemodynamic responses to hemorrhage. Therefore, the capacity to respond to a physiological challenge to body fluid homeostasis may be compromised following RDN.
Authors: Nathalia R Lopes; Maycon I O Milanez; Beatriz S Martins; Amanda C Veiga; Giovanna R Ferreira; Guiomar N Gomes; Adriana C Girardi; Polliane M Carvalho; Fernando N Nogueira; Ruy R Campos; Cássia T Bergamaschi; Erika E Nishi Journal: Pflugers Arch Date: 2020-01-10 Impact factor: 3.657
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Authors: Reetu R Singh; Zoe McArdle; Harshil Singh; Lindsea C Booth; Clive N May; Geoffrey A Head; Karen M Moritz; Markus P Schlaich; Kate M Denton Journal: Sci Rep Date: 2021-07-20 Impact factor: 4.379
Authors: Yann Vuignier; Eric Grouzmann; Olivier Muller; Nima Vakilzadeh; Mohamed Faouzi; Marc P Maillard; Salah D Qanadli; Michel Burnier; Grégoire Wuerzner Journal: Front Cardiovasc Med Date: 2018-05-23