Training heart failure patients with reduced ejection fraction attenuates muscle sympathetic nerve activation during mild dynamic exercise.
Catherine F Notarius, Philip J Millar, Daniel A Keir, Hisayoshi Murai, Nobuhiko Haruki, Emma O'Donnell, Susan Marzolini, Paul Oh, John S Floras
Author Information
Catherine F Notarius: Division of Cardiology, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Philip J Millar: Division of Cardiology, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. ORCID
Daniel A Keir: Division of Cardiology, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Hisayoshi Murai: Division of Cardiology, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Nobuhiko Haruki: Division of Cardiology, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Emma O'Donnell: Division of Cardiology, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Susan Marzolini: Cardiovascular Prevention and Rehabilitation Program, Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada.
Paul Oh: Cardiovascular Prevention and Rehabilitation Program, Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada.
John S Floras: Division of Cardiology, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Muscle sympathetic nerve activity (MSNA) decreases during low-intensity dynamic one-leg exercise in healthy subjects but increases in patients with heart failure with reduced ejection fraction (HFrEF). We hypothesized that increased peak oxygen uptake (V̇o) after aerobic training would be accompanied by less sympathoexcitation during both mild and moderate one-leg dynamic cycling, an attenuated muscle metaboreflex, and greater skin vasodilation. We studied 27 stable, treated HFrEF patients (6 women; mean age: 65 ± 2 SE yr; mean left ventricular ejection fraction: 30 ± 1%) and 18 healthy age-matched volunteers (6 women; mean age: 57 ± 2 yr). We assessed V̇o (open-circuit spirometry) and the skin microcirculatory response to reactive hyperemia (laser flowmetry). Fibular MSNA (microneurography) was recorded before and during one-leg cycling (2 min unloaded and 2 min at 50% of V̇o) and, to assess the muscle metaboreflex, during posthandgrip ischemia (PHGI). HFrEF patients were evaluated before and after 6 mo of exercise-based cardiac rehabilitation. Pretraining V̇o and skin vasodilatation were lower ( < 0.001) and resting MSNA higher ( = 0.01) in HFrEF than control subjects. Training improved V̇o (+3.0 ± 1.0 mL·kg·min; < 0.001) and cutaneous vasodilation and diminished resting MSNA (-6.0 ± 2.0, = 0.01) plus exercise MSNA during unloaded (-4.0 ± 2.5, = 0.04) but not loaded cycling (-1.0 ± 4.0 bursts/min, = 0.34) and MSNA during PHGI ( < 0.05). In HFrEF patients, exercise training lowers MSNA at rest, desensitizes the sympathoexcitatory metaboreflex, and diminishes MSNA elicited by mild but not moderate cycling. Training-induced downregulation of resting MSNA and attenuated reflex sympathetic excitation may improve exercise capacity and survival.
