Abstract
Chronic underperfusion of the skeletal muscle tissues is a contributor to a decrease in exercise capacity in patients with heart failure with reduced ejection fraction (HFrEF). This underperfusion is due, at least in part, to impaired nitric oxide (NO) bioavailability. Oral inorganic nitrate supplementation increases NO bioavailability and may be used to improve exercise capacity, vascular function, and mitochondrial respiration. Sixteen patients with HFrEF (fifteen men, 63 ± 4 yr, body mass index: 31.8 ± 2.1 kg/m2) participated in a randomized, double-blind, crossover design study. Following consumption of either nitrate-rich beetroot juice (16 mmol nitrate/day) or a nitrate-depleted placebo for 5 days, participants completed separate visits for assessment of exercise capacity, endothelial function, and muscle mitochondrial respiration. Participants then had a 2-wk washout before completion of the same protocol with the other intervention. Statistical significance was set a priori at P < 0.05, and between-treatment differences were analyzed via paired t test analysis. Following nitrate supplementation, both plasma nitrate and nitrite increased (933%, P < 0.001 and 94%, P < 0.05, respectively). No differences were observed for peak oxygen consumption (nitrate: 18.5 ± 1.4 mL·kg-1·min-1, placebo: 19.3 ± 1.4 mL·kg-1·min-1; P = 0.13) or time to exhaustion (nitrate: 1,165 ± 92 s, placebo: 1,207 ± 96 s; P = 0.16) following supplementation. There were no differences between interventions for measures of vascular function, mitochondrial respiratory function, or protein expression (all P > 0.05). Inorganic nitrate supplementation did not improve exercise capacity and skeletal muscle mitochondrial respiratory function in HFrEF. Future studies should explore alternative interventions to improve peripheral muscle tissue function in HFrEF.NEW & NOTEWORTHY This is the largest study to date to examine the effects of inorganic nitrate supplementation in patients with heart failure with reduced ejection fraction (HFrEF) and the first to include measures of vascular function and mitochondrial respiration. Although daily supplementation increased plasma nitrite, our data indicate that supplementation with inorganic nitrate as a standalone treatment is ineffective at improving exercise capacity, vascular function, or mitochondrial respiration in patients with HFrEF.
Highlights
Patients with chronic heart failure (CHF) are characterised by reduced aerobic capacity (VO2peak) and early fatigue [6]
This is the largest study to date to examine the effects of inorganic nitrate supplementation in patients with heart failure reduced ejection fraction (HFrEF) and the first to include measures of vascular function and mitochondrial respiration
While daily supplementation increased plasma nitrite, our data indicates that supplementation with inorganic nitrate as a standalone treatment is ineffective at improving exercise capacity, vascular function or mitochondrial respiration in patients with HFrEF
Summary
Patients with chronic heart failure (CHF) are characterised by reduced aerobic capacity (VO2peak) and early fatigue [6]. It is well accepted that impairments in peripheral tissues have a significant contribution to the reduced exercise capacity in patients with CHF [3]. It is important to uncover whether increasing NO bioavailability through exogenous NO precursors can improve peripheral function and exercise capacity in patients with CHF. Chronic under perfusion of the skeletal muscle tissues is a contributor to a decrease in exercise capacity in patients with heart failure reduced ejection fraction (HFrEF). This under perfusion is due, at least in part, to impaired nitric oxide (NO) bioavailability.
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