Heart failure with preserved ejection fraction diminishes peripheral hemodynamics and accelerates exercise-induced neuromuscular fatigue.

This study investigated the impact of HFpEF on neuromuscular fatigue and peripheral hemodynamics during small muscle mass exercise not limited by cardiac output. Eight HFpEF patients (NYHA II-III, ejection-fraction: 61 ± 2%) and eight healthy controls performed dynamic knee extension exercise (80% peak workload) to task failure and maximal intermittent quadriceps contractions (8 × 15 s). Controls repeated knee extension at the same absolute intensity as HFpEF. Leg blood flow (QL) was quantified using Doppler ultrasound. Pre/postexercise changes in quadriceps twitch torque (ΔQtw; peripheral fatigue), voluntary activation (ΔVA; central fatigue), and corticospinal excitability were quantified. At the same relative intensity, HFpEF (24 ± 5 W) and controls (42 ± 6 W) had a similar time-to-task failure (∼10 min), ΔQtw (∼50%), and ΔVA (∼6%). This resulted in a greater exercise-induced change in neuromuscular function per unit work in HFpEF, which was significantly correlated with a slower QL response time. Knee extension exercise at the same absolute intensity resulted in an ∼40% lower QL and greater ΔQtw and ΔVA in HFpEF than in controls. Corticospinal excitability remained unaltered during exercise in both groups. Finally, despite a similar ΔVA, ΔQtw was larger in HFpEF versus controls during isometric exercise. In conclusion, HFpEF patients are characterized by a similar development of central and peripheral fatigue as healthy controls when tested at the same relative intensity during exercise not limited by cardiac output. However, HFpEF patients have a greater susceptibility to neuromuscular fatigue during exercise at a given absolute intensity, and this impairs functional capacity. The patients' compromised QL response to exercise likely accounts, at least partly, for the patients' attenuated fatigue resistance.NEW & NOTEWORTHY The susceptibility to neuromuscular fatigue during exercise is substantially exaggerated in individuals with heart failure with a preserved ejection fraction. The faster rate of fatigue development is associated with the compromised peripheral hemodynamic response characterizing these patients during exercise. Given the role of neuromuscular fatigue as a factor limiting exercise, this impairment likely accounts for a significant portion of the exercise intolerance typical for this population.

Human skeletal muscle feed arteries: evidence of regulatory potential.

AIM: Recently, it has been recognized that human skeletal muscle feed arteries can be harvested during exploratory surgery for melanoma. This approach provides vessels for in vitro study from a wide spectrum of relatively healthy humans. Although, the regulatory role of skeletal muscle feed arteries in rodent models has been documented, whether such vessels in humans possess this functionality is unknown. METHODS: Therefore, skeletal muscle feed arteries (~950 µm OD) from 10 humans (48 ± 4, 27-64 years) were studied using pressure myography. Vessel function was assessed using potassium chloride (KCl), phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP) concentration-response curves (CRCs) to characterize non-receptor and receptor-mediated vasoconstriction as well as endothelium-dependent and independent vasodilation respectively. To understand the physiological relevance of the diameter changes as a result of pharmacological stimulation, the estimated conductance ratio (CR) was calculated. RESULTS: Vessel function protocols revealed significant vasoconstriction in response to PE and KCl (35 ± 6; 43 ± 9%vasoconstriction, respectively) and significant vasodilation with ACh and SNP (85 ± 7; 121 ± 17% vasodilation, respectively). Both PE and KCl significantly reduced the CR (0.26 ± 0.05 and 0.23 ± 0.07, respectively), whereas ACh and SNP increased the CR (2.56 ± 0.10 and 5.32 ± 1.3, respectively). CONCLUSION: These novel findings provide evidence that human skeletal muscle feed arteries are capable of generating significant diameter changes that would translate into significant changes in vascular conductance. Thus, human skeletal muscle feed arteries likely play a significant role in regulating vascular conductance and subsequently blood flow in vivo.