Key result
Intra-arterial phentolamine increased leg blood flow more in HFrEF patients than controls at rest and during exercise, implying increased alpha-adrenergic vasoconstriction.
Why the study?
Patients with HFrEF experience impaired limb blood flow during exercise, which may be caused by a disease-related increase in alpha-adrenergic receptor vasoconstriction.
Does α-adrenergic receptor blockade with phentolamine improve skeletal muscle blood flow during exercise more in HFrEF patients compared to healthy controls?
Does α-adrenergic receptor blockade with phentolamine improve skeletal muscle blood flow during exercise more in HFrEF patients compared to healthy controls?
In patients with HFrEF, an exaggerated α-adrenergic vasoconstriction restrains skeletal muscle blood flow during exercise, which may contribute to diminished exercise capacity.
Answers are grounded in this paper and cite their sources.
May limit muscle perfusion during exercise in HFrEF; leaves open whether α-blockade improves capacity in trials.
Patients suffering from heart failure with reduced ejection fraction (HFrEF) experience impaired limb blood flow during exercise, which may be due to a disease-related increase in α-adrenergic receptor vasoconstriction. Thus, in eight patients with HFrEF (63 ± 4 yr) and eight well-matched controls (63 ± 2 yr), we examined changes in leg blood flow (Doppler ultrasound) during intra-arterial infusion of phenylephrine (PE; an α 1 -adrenergic receptor agonist) and phentolamine (Phen; a nonspecific α-adrenergic receptor antagonist) at rest and during dynamic single-leg knee-extensor exercise (0, 5, and 10 W). At rest, the PE-induced reduction in blood flow was significantly attenuated in patients with HFrEF (−15 ± 7%) compared with controls (−36 ± 5%). During exercise, the controls exhibited a blunted reduction in blood flow induced by PE (−12 ± 4, −10 ± 4, and −9 ± 2% at 0, 5, and 10 W, respectively) compared with rest, while the PE-induced change in blood flow was unchanged compared with rest in the HFrEF group (−8 ± 5, −10 ± 3, and −14 ± 3%, respectively). Phen administration increased leg blood flow to a greater extent in the HFrEF group at rest (+178 ± 34% vs. +114 ± 28%, HFrEF vs. control) and during exercise (36 ± 6, 37 ± 7, and 39 ± 6% vs. 13 ± 3, 14 ± 1, and 8 ± 3% at 0, 5, and 10 W, respectively, in HFrEF vs. control). Together, these findings imply that a HFrEF-related increase in α-adrenergic vasoconstriction restrains exercising skeletal muscle blood flow, potentially contributing to diminished exercise capacity in this population.
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Barrett‐O’Keefe et al. (2019) studied Heart failure with reduced ejection fraction (HFrEF) (n=16). Intra-arterial infusion of phenylephrine and phentolamine vs. Well-matched controls was evaluated on Change in leg blood flow during intra-arterial infusion of phentolamine at rest. Intra-arterial phentolamine increased leg blood flow more in HFrEF patients than controls at rest and during exercise, implying increased alpha-adrenergic vasoconstriction.
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