Journal article
α-Adrenergic regulation of skeletal muscle blood flow during exercise in patients with heart failure with preserved ejection fraction
The Journal of physiology, Vol.602(14), pp.3401-3422
07/01/2024
DOI: 10.1113/JP285526
PMCID: PMC11250769
PMID: 38843407
Abstract
Heart failure with preserved ejection fraction (HFpEF) has been characterized by lower blood flow to exercising limbs and lower peak oxygen utilization (
), possibly associated with disease-related changes in sympathetic (α-adrenergic) signaling. Thus, in seven patients with HFpEF (70 ± 6 years, 3 female/4 male) and seven controls (CON) (66 ± 3 years, 3 female/4 male), we examined changes (%Δ) in leg blood flow (LBF, Doppler ultrasound) and leg
to intra-arterial infusion of phentolamine (PHEN, α-adrenergic antagonist) or phenylephrine (PE, α
-adrenergic agonist) at rest and during single-leg knee-extension exercise (0, 5 and 10 W). At rest, the PHEN-induced increase in LBF was not different between groups, but PE-induced reductions in LBF were lower in HFpEF (-16% ± 4% vs. -26% ± 5%, HFpEF vs. CON; P < 0.05). During exercise, the PHEN-induced increase in LBF was greater in HFpEF at 10 W (16% ± 8% vs. 8% ± 5%; P < 0.05). PHEN increased leg
in HFpEF (10% ± 3%, 11% ± 6%, 15% ± 7% at 0, 5 and 10 W; P < 0.05) but not in controls (-1% ± 9%, -4% ± 2%, -1% ± 5%; P = 0.24). The 'magnitude of sympatholysis' (PE-induced %Δ LBF at rest - PE-induced %Δ LBF during exercise) was lower in patients with HFpEF (-6% ± 4%, -6% ± 6%, -7% ± 5% vs. -13% ± 6%, -17% ± 5%, -20% ± 5% at 0, 5 and 10 W; P < 0.05) and was positively related to LBF, leg oxygen delivery, leg
, and the PHEN-induced increase in LBF (P < 0.05). Together, these data indicate that excessive α-adrenergic vasoconstriction restrains blood flow and limits
of the exercising leg in patients with HFpEF, and is related to impaired functional sympatholysis in this patient group. KEY POINTS: Sympathetic (α-adrenergic)-mediated vasoconstriction is exaggerated during exercise in patients with heart failure with preserved ejection fraction (HFpEF), which may contribute to limitations of blood flow, oxygen delivery and oxygen utilization in the exercising muscle. The ability to adequately attenuate α
-adrenergic vasoconstriction (i.e. functional sympatholysis) within the vasculature of the exercising muscle is impaired in patients with HFpEF. These observations extend our current understanding of HFpEF pathophysiology by implicating excessive α-adrenergic restraint and impaired functional sympatholysis as important contributors to disease-related impairments in exercising muscle blood flow and oxygen utilization in these patients.
Details
- Title: Subtitle
- α-Adrenergic regulation of skeletal muscle blood flow during exercise in patients with heart failure with preserved ejection fraction
- Creators
- Jeremy K Alpenglow - University of UtahKanokwan Bunsawat - University of UtahMichael A Francisco - Geriatric Research Education and Clinical CenterRyan M Broxterman - University of UtahJesse C Craig - University of UtahJarred J Iacovelli - University of UtahJoshua C Weavil - Geriatric Research Education and Clinical CenterJonathan D Harrison - University of UtahDavid E Morgan - University of UtahNatalie A Silverton - University of UtahVan R Reese - University of UtahChristy L Ma - Department of Internal Medicine, Division of Cardiovascular Medicine, Salt Lake City, UT, USAJohn J Ryan - University of UtahD Walter Wray - University of Utah
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.602(14), pp.3401-3422
- DOI
- 10.1113/JP285526
- PMID
- 38843407
- PMCID
- PMC11250769
- NLM abbreviation
- J Physiol
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Grant note
- I8POST33960192 / American Heart Association (AHA) CX002152 / US Department of Veterans Affairs (VA) R01 HL162856 / NHLBI NIH HHS HL139451 / HHS | National Institutes of Health (NIH) IK2RX003670 / US Department of Veterans Affairs (VA) IK2 RX003670 / RRD VA IK2 RX003913 / RRD VA HL162856 / HHS | National Institutes of Health (NIH) I01 CX002152 / CSRD VA T32 HL139451 / NHLBI NIH HHS
- Language
- English
- Date published
- 07/01/2024
- Academic Unit
- Health, Sport, and Human Physiology
- Record Identifier
- 9984948142502771
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