Impact of Acute Antioxidant and Tetrahydrobiopterin (BH4) Administration on Locomotor Muscle Microvascular Function in Patients With Heart Failure | Circulation: Heart Failure
BACKGROUND: Peripheral microvascular dysfunction is a hallmark feature of both heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) pathophysiology, due partly to impairments in nitric oxide signaling secondary to tetrahydrobiopterin (BH4) deficiency and oxidative stress. METHODS: Using a randomized, double-blind, placebo-controlled crossover design, this study examined the impact of enteral BH4 (10 mg/kg), an antioxidant cocktail (AOx), and coadministration of these 2 agents (BH4+AOx) on microvascular function in patients with HFrEF (n=14, 64±10 years) and HFpEF (n=19, 74±9 years). Passive limb movement was utilized to assess locomotor muscle microvascular function, and biomarkers of inflammation and oxidative damage were measured. RESULTS: Compared with placebo, the peak change in leg blood flow was not statistically different after AOx administration (HFrEF, P=0.60; HFpEF, P=0.61), but improved following BH4 (P=0.033) and BH4+AOx (P=0.019) in
