Short-term effects of catheter-based renal denervation on cardiac sympathetic drive and cardiac baroreflex function in heart failure.
OBJECTIVE
Sympathetic drive, especially to the heart, is elevated in heart failure and is strongly associated with poor outcome. The mechanisms causing the increased sympathetic drive to the heart remain poorly understood. Catheter-based renal denervation (RDN), which reduces blood pressure (BP) and sympathetic drive in hypertensive patients, is a potential treatment in heart failure. The aim of this study was to investigate the short-term effects of catheter-based RDN on BP, heart rate (HR) and cardiac sympathetic nerve activity (CSNA) and on baroreflex function in a conscious, large animal model of heart failure.


METHODS
Adult Merino ewes were paced into heart failure (ejection fraction<40%) and then instrumented to directly record CSNA. The resting levels and baroreflex control of CSNA and HR were measured before and 24h after bilateral renal (n=6) or sham (n=6) denervation. RDN was performed using the Symplicity Flex Catheter System® (Medtronic) using the same algorithm as in patients.


RESULTS
Catheter-based RDN significantly reduced resting diastolic BP (P<0.01) and mean arterial blood pressure (P<0.05), but did not change resting HR or CSNA compared with sham denervation. Renal denervation reduced the BP at which CSNA was at 50% of maximum (BP50; P<0.005) compared with sham denervation.


CONCLUSIONS
In an ovine model of heart failure, catheter-based RDN did not reduce resting CSNA in the short-term. There was, however, a lack of a reflex increase in CSNA in response to the fall in arterial pressure due to a leftward shift in the baroreflex control of CSNA, which may be due to denervation of renal efferent and/or afferent nerves.
Florey Institute of Neuroscience and Mental Health, Melbourne, Australia. Electronic address: lindsea.booth@florey.edu.au.
Lindsea C
LC
Booth
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Markus P
MP
Schlaich
Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; Department of Physiology, Cardiovascular Division, Federal University of São Paulo, São Paulo, Brazil.
Erika E
EE
Nishi
Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.
Song T
ST
Yao
Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai, China.
Jianzhong
J
Xu
Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; Department of Physiology, University of Auckland, Auckland, New Zealand.
Rohit
R
Ramchandra
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Gavin W
GW
Lambert
Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.
Clive N
CN
May
D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D002404:Catheterization / Q000379:methods*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000601:surgery*; D006339:Heart Rate / Q000502:physiology; D007668:Kidney / Q000294:innervation* / Q000601:surgery*; D012756:Sheep; D013562:Sympathectomy / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
Animal model; Arterial baroreflex; Cardiac sympathetic nerve activity; Radiofrequency-ablation; Renal denervation