Journal article
Impact of Acute Antioxidant and Tetrahydrobiopterin (BH4) Administration on Locomotor Muscle Microvascular Function in Patients With Heart Failure
Circulation. Heart failure, Vol.18(6), pp.593-604
06/2025
DOI: 10.1161/CIRCHEARTFAILURE.124.012446
PMCID: PMC12173787
PMID: 40270242
Abstract
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 both HFrEF (placebo: 234±31; BH4: 357±45; BH4+AOx: 355±49 mL/min) and HFpEF (placebo: 269±33; BH4: 367±47; BH4+AOx: 394±65 mL/min). The total hyperemic response to passive limb movement (leg blood flow area under the curve) was not statistically different across treatments in patients with HFrEF (P=0.29), but increased following BH4 (P=0.016) and BH4+AOx (P=0.040) in the HFpEF group. CRP (C-reactive protein) was lower following BH4 (P=0.007) and BH4+AOx (P=0.007) in HFpEF (placebo: 4268±547; BH4: 2721±391; BH4+AOx: 2779±376 ng/mL), but was not statistically different in HFrEF (P=0.39).
CONCLUSIONS:
Together, these results provide new evidence for the efficacy of acute BH4 administration to improve some aspects of locomotor muscle microvascular function in patients with HFrEF and HFpEF, with no apparent benefit of AOx administration, alone or in combination with BH4, in either group. These findings lend further conceptual support for the nitric oxide pathway as a modifiable target in the treatment of heart failure.
Details
- Title: Subtitle
- Impact of Acute Antioxidant and Tetrahydrobiopterin (BH4) Administration on Locomotor Muscle Microvascular Function in Patients With Heart Failure
- Creators
- Stephen M. Ratchford - University of UtahHeather L. Clifton - University of UtahJayson R Gifford - University of UtahD. Taylor LaSalle - University of UtahTaylor S. Thurston - University of UtahKanokwan Bunsawat - Health, Sport, and Human PhysiologyJeremy K Alpenglow - University of UtahJosephine B. Wright - University of UtahMarkus Amann - University of UtahJohn J Ryan - University of UtahD. Walter Wray - University of Utah
- Resource Type
- Journal article
- Publication Details
- Circulation. Heart failure, Vol.18(6), pp.593-604
- DOI
- 10.1161/CIRCHEARTFAILURE.124.012446
- PMID
- 40270242
- PMCID
- PMC12173787
- NLM abbreviation
- Circ Heart Fail
- ISSN
- 1941-3289
- eISSN
- 1941-3297
- Publisher
- Lippincott Williams & Wilkins
- Language
- English
- Date published
- 06/2025
- Academic Unit
- Health, Sport, and Human Physiology
- Record Identifier
- 9984948046502771
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