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Peripheral chemoreflex activation contributes to sympathetic baroreflex impairment in chronic heart failure

Despas, Fabiena,b,c; Lambert, Elisabethd; Vaccaro, Angelicaa,b; Labrunee, Marca,b; Franchitto, Nicolasa,b; Lebrin, Marinea,b; Galinier, Michela,b,d; Senard, Jean-Michela,b,c; Lambert, Gavind; Esler, Murrayd; Pathak, Atula,b,c,d,e

doi: 10.1097/HJH.0b013e328350136c
ORIGINAL PAPERS: Sympathetic activity
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Background: Chemoreflex-mediated sympathetic activation contributes to both initiation and progression of chronic heart failure (CHF).

Method: To study the direct role of increased peripheral chemosensitivity in reducing sympathetic baroreflex function in CHF patients, we compared sympathetic baroreflex function, assessed by the slope of the relationship between muscle sympathetic nerve activity (MSNA) and DBP, in CHF patients with augmented (n = 18) and normal (n = 20) peripheral chemosensitivity. Using a double-blind, randomized, vehicle-controlled study, we examined the effect of chemoreflex deactivation (by breathing 100% oxygen for 15 min) on sympathetic baroreflex function in CHF patients with elevated and with normal chemosensitivity.

Results: Baseline MSNA was elevated (60.6 ± 3.2 vs. 48.9 ± 3.7 bursts/min, P < 0.05) and sympathetic baroreflex function impaired (3.06 ± 0.55 vs. 5.51 ± 0.69 %bursts/mmHg, P < 0.05) in CHF patients with augmented peripheral chemosensitivity compared with controls. Administration of 100% oxygen led to a significant decrease in MSNA (from 60.5 ± 3.2 to 52.6 ± 3.2 bursts/min, P < 0.001) and increase in sympathetic baroreflex (from 2.95 ± 0.56 to 6.18 ± 0.77, P < 0.001) in CHF patients with enhanced chemoreflex sensitivity. In contrast, neither room air nor 100% oxygen changed MSNA, hemodynamics or sympathetic baroreflex function in CHF patients with normal chemosensitivity.

Conclusion: We report for the first time that increased peripheral chemoreflex sensitivity directly decreases sympathetic baroreflex function in CHF patients. This interaction contributes to sympathetic overactivity and blunted sympathetic baroreflex function of CHF patients and may explain how chemoreceptors contribute to the bad prognosis of CHF patients.

aInstitut National de la Sante et de la Recherche Médicale, UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires

bUniversité de Toulouse III Paul Sabatier

cDepartment of Clinical Pharmacology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France

dHuman Neurotransmitter Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia

eDepartment of Cardiology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France

Correspondence to Fabien Despas, PharmD, PhD, University Hospital Toulouse, UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, F-31432 Toulouse, France. Tel: +33 686273359l; fax: +33 561255116; e-mail: fabien.despas@univ-tlse3.fr

Abbreviations: BP, blood pressure; CHF, chronic heart failure; HR, heart rate; LVEF, left ventricular ejection fraction; MSNA, muscle sympathetic nerve activity; NYHA, New York Heart Association

Received 30 September, 2011

Revised 22 November, 2011

Accepted 6 December, 2011

This work has been partly presented at ESH Meeting, 17–21 June 2011, Milan, Italy.

© 2012 Lippincott Williams & Wilkins, Inc.