title: Dietary nitrate supplementation and exercise tolerance in patients with heart failure with reduced ejection fraction.
abstract: Endothelial dysfunction and reduced nitric oxide (NO) signaling are key abnormalities leading to skeletal muscle oxygen delivery-utilization mismatch and poor physical capacity in patients with heart failure with reduced ejection fraction (HFrEF). Oral inorganic nitrate supplementation provides an exogenous source of NO that may enhance locomotor muscle function and oxygenation with consequent improvement in exercise tolerance in HFrEF. Thirteen patients (left ventricular ejection fraction ≤40%) were enrolled in a double-blind, randomized crossover study to receive concentrated nitrate-rich (nitrate) or nitrate-depleted (placebo) beetroot juice for 9 days. Low- and high-intensity constant-load cardiopulmonary exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary oxygen uptake, quadriceps muscle oxygenation (near-infrared spectroscopy), and blood lactate concentration. Ten patients completed the study with no adverse clinical effects. Nitrate-rich supplementation resulted in significantly higher plasma nitrite concentration compared with placebo (240 ± 48 vs. 56 ± 8 nM, respectively; P < 0.05). There was no significant difference in the primary outcome of time to exercise intolerance between nitrate and placebo (495 ± 53 vs. 489 ± 58 s, respectively; P > 0.05). Similarly, there were no significant differences in central hemodynamics, arterial blood pressure, pulmonary oxygen uptake kinetics, skeletal muscle oxygenation, or blood lactate concentration from rest to low- or high-intensity exercise between conditions. Oral inorganic nitrate supplementation with concentrated beetroot juice did not present with beneficial effects on central or peripheral components of the oxygen transport pathway thereby failing to improve exercise tolerance in patients with moderate HFrEF.
authors: Department of Medicine, Division of Respirology, Laboratory of Clinical Exercise Physiology, Queen's University, Kingston, Ontario, Canada; d.hirai@yahoo.com.|Department of Medicine, Respiratory Division, Pulmonary Function and Clinical Exercise Physiology Unit, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors: Daniel M
authors: DM
authors: Hirai
authors: Department of Medicine, Division of Respirology, Laboratory of Clinical Exercise Physiology, Queen's University, Kingston, Ontario, Canada.
authors: Joel T
authors: JT
authors: Zelt
authors: Department of Medicine, Division of Respirology, Laboratory of Clinical Exercise Physiology, Queen's University, Kingston, Ontario, Canada.
authors: Joshua H
authors: JH
authors: Jones
authors: Department of Medicine, Division of Respirology, Laboratory of Clinical Exercise Physiology, Queen's University, Kingston, Ontario, Canada.
authors: Luiza G
authors: LG
authors: Castanhas
authors: School of Kinesiology and Health Studies, Human Vascular Control Laboratory, Queen's University, Kingston, Ontario, Canada.
authors: Robert F
authors: RF
authors: Bentley
authors: Department of Medicine, Division of Cardiology, Queen's University, Kingston, Ontario, Canada; and.
authors: Wendy
authors: W
authors: Earle
authors: Department of Medicine, Division of Cardiology, Queen's University, Kingston, Ontario, Canada; and.
authors: Patti
authors: P
authors: Staples
authors: School of Kinesiology and Health Studies, Human Vascular Control Laboratory, Queen's University, Kingston, Ontario, Canada.
authors: Michael E
authors: ME
authors: Tschakovsky
authors: Department of Medicine, Division of Cardiology, Queen's University, Kingston, Ontario, Canada; and.
authors: John
authors: J
authors: McCans
authors: Department of Medicine, Division of Respirology, Respiratory Investigation Unit, Queen's University, Kingston, Ontario, Canada.
authors: Denis E
authors: DE
authors: O'Donnell
authors: Department of Medicine, Division of Respirology, Laboratory of Clinical Exercise Physiology, Queen's University, Kingston, Ontario, Canada.
authors: J Alberto
authors: JA
authors: Neder
mesh_terms: D019587:Dietary Supplements; D004311:Double-Blind Method; D005080:Exercise Test / Q000187:drug effects; D017079:Exercise Tolerance / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage*; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D009566:Nitrates
keywords: blood pressure; nitric oxide; nitrite; oxygen consumption; skeletal muscle