Catheter-Based Renal Denervation Exacerbates Blood Pressure Fall During Hemorrhage

Reetu R. Singh, Varsha Sajeesh, Lindsea C. Booth, Zoe McArdle, Clive N. May, Geoffrey A. Head, Karen M. Moritz, Markus P. Schlaich, Kate M. Denton

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)951-964
Number of pages14
JournalJournal of the American College of Cardiology
Volume69
Issue number8
DOIs
Publication statusPublished - 28 Feb 2017

Keywords

  • chronic kidney disease
  • hypertension
  • mean arterial pressure
  • plasma renin activity
  • sheep

Cite this

Singh, Reetu R. ; Sajeesh, Varsha ; Booth, Lindsea C. ; McArdle, Zoe ; May, Clive N. ; Head, Geoffrey A. ; Moritz, Karen M. ; Schlaich, Markus P. ; Denton, Kate M. / Catheter-Based Renal Denervation Exacerbates Blood Pressure Fall During Hemorrhage. In: Journal of the American College of Cardiology. 2017 ; Vol. 69, No. 8. pp. 951-964.
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title = "Catheter-Based Renal Denervation Exacerbates Blood Pressure Fall During Hemorrhage",
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.",
keywords = "chronic kidney disease, hypertension, mean arterial pressure, plasma renin activity, sheep",
author = "Singh, {Reetu R.} and Varsha Sajeesh and Booth, {Lindsea C.} and Zoe McArdle and May, {Clive N.} and Head, {Geoffrey A.} and Moritz, {Karen M.} and Schlaich, {Markus P.} and Denton, {Kate M.}",
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Catheter-Based Renal Denervation Exacerbates Blood Pressure Fall During Hemorrhage. / Singh, Reetu R.; Sajeesh, Varsha; Booth, Lindsea C.; McArdle, Zoe; May, Clive N.; Head, Geoffrey A.; Moritz, Karen M.; Schlaich, Markus P.; Denton, Kate M.

In: Journal of the American College of Cardiology, Vol. 69, No. 8, 28.02.2017, p. 951-964.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Catheter-Based Renal Denervation Exacerbates Blood Pressure Fall During Hemorrhage

AU - Singh, Reetu R.

AU - Sajeesh, Varsha

AU - Booth, Lindsea C.

AU - McArdle, Zoe

AU - May, Clive N.

AU - Head, Geoffrey A.

AU - Moritz, Karen M.

AU - Schlaich, Markus P.

AU - Denton, Kate M.

PY - 2017/2/28

Y1 - 2017/2/28

N2 - 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.

AB - 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.

KW - chronic kidney disease

KW - hypertension

KW - mean arterial pressure

KW - plasma renin activity

KW - sheep

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