title: Exercise training improves neurovascular control and calcium cycling gene expression in patients with heart failure with cardiac resynchronization therapy.
abstract: Heart failure (HF) is characterized by decreased exercise capacity, attributable to neurocirculatory and skeletal muscle factors. Cardiac resynchronization therapy (CRT) and exercise training have each been shown to decrease muscle sympathetic nerve activity (MSNA) and increase exercise capacity in patients with HF. We hypothesized that exercise training in the setting of CRT would further reduce MSNA and vasoconstriction and would increase Ca2+-handling gene expression in skeletal muscle in patients with chronic systolic HF. Thirty patients with HF, ejection fraction <35% and CRT for 1 mo, were randomized into two groups: exercise-trained (ET, n = 14) and untrained (NoET, n = 16) groups. The following parameters were compared at baseline and after 4 mo in each group: V̇o2 peak, MSNA (microneurography), forearm blood flow, and Ca2+-handling gene expression in vastus lateralis muscle. After 4 mo, exercise duration and V̇o2 peakwere significantly increased in the ET group (P = 0.04 and P = 0.01, respectively), but not in the NoET group. MSNA was significantly reduced in the ET (P = 0.001), but not in NoET, group. Similarly, forearm vascular conductance significantly increased in the ET (P = 0.0004), but not in the NoET, group. The expression of the Na+/Ca2+exchanger (P = 0.01) was increased, and ryanodine receptor expression was preserved in ET compared with NoET. In conclusion, the exercise training in the setting of CRT improves exercise tolerance and neurovascular control and alters Ca2+-handling gene expression in the skeletal muscle of patients with systolic HF. These findings highlight the importance of including exercise training in the treatment of patients with HF even following CRT.
authors: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors: Thais S
authors: TS
authors: Nobre
authors: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors: Ligia M
authors: LM
authors: Antunes-Correa
authors: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors: Raphaela V
authors: RV
authors: Groehs
authors: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors: Maria Janieire N N
authors: MJ
authors: Alves
authors: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors: Adriana O
authors: AO
authors: Sarmento
authors: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors: Aline V
authors: AV
authors: Bacurau
authors: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors: Ursula
authors: U
authors: Urias
authors: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors: Guilherme B
authors: GB
authors: Alves
authors: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors: Maria Urbana P B
authors: MU
authors: Rondon
authors: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors: Patrícia C
authors: 0000-0002-4750-6506
authors: PC
authors: Brum
authors: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors: Martino
authors: M
authors: Martinelli
authors: Department of Medicine (Cardiology) and Physiology, Geffen School of Medicine at UCLA, University of California, Los Angeles, California.
authors: Holly R
authors: HR
authors: Middlekauff
authors: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil; cndnegrao@incor.usp.br.|School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors: Carlos E
authors: CE
authors: Negrao
mesh_terms: D002118:Calcium / Q000378:metabolism*; D058406:Cardiac Resynchronization Therapy; D004452:Echocardiography; D015444:Exercise; D005080:Exercise Test; D005081:Exercise Therapy; D017079:Exercise Tolerance; D005260:Female; D005542:Forearm / Q000098:blood supply; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism; D000069336:Neurovascular Coupling; D010101:Oxygen Consumption; D052097:Quadriceps Muscle / Q000294:innervation / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D019831:Sodium-Calcium Exchanger / Q000235:genetics; D013564:Sympathetic Nervous System / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D002118:Calcium
keywords: cardiac resynchronization; exercise; heart failure; neurovascular control; skeletal muscle