Abnormal neurovascular control during central and peripheral chemoreceptors stimulation in heart failure patients with preserved ejection fraction.

PURPOSE: Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF. METHODS: Patients aged 55-80 years with symptoms of heart failure, body mass index ≤ 35 kg/m2, left ventricular ejection fraction > 50%, left atrial volume index > 34 mL/m2, left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e' index) ≥ 13, and BNP levels > 35 pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O2 and 90% N2, with CO2 titrated) and central chemoreceptors stimulation (7% CO2 and 93% O2) were conducted for 3 min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography. RESULTS: During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF. CONCLUSIONS: Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction.

Dietary nitrate supplementation increases nitrate and nitrite concentrations in human skin interstitial fluid.

Acute dietary nitrate (NO3-) supplementation can increase [NO3-], but not nitrite ([NO2-]), in human skeletal muscle, though its effect on [NO3-] and [NO2-] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO3--rich beetroot juice (BR; 9.6 mmol NO3-), and 6 young adults ingested 140 mL of a NO3--depleted placebo (PL). Skin dialysate, acquired through intradermal microdialysis, and venous blood samples were collected at baseline and every hour post-ingestion up to 4 h to assess dialysate and plasma [NO3-] and [NO2-]. The relative recovery rate of NO3- and NO2- through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO3-] and [NO2-]. Baseline [NO3-] was lower, whereas baseline [NO2-] was higher in the skin interstitial fluid relative to plasma (both P < 0.001). Acute BR ingestion increased [NO3-] and [NO2-] in the skin interstitial fluid and plasma (all P < 0.001), with the magnitude being smaller in the skin interstitial fluid (e.g., 183 ± 54 vs. 491 ± 62 µM for Δ[NO3-] from baseline and 155 ± 190 vs. 217 ± 204 nM for Δ[NO2-] from baseline at 3 h post BR ingestion, both P ≤ 0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO2-] post BR ingestion was higher, whereas [NO3-] was lower relative to plasma (all P < 0.001). These findings extend our understanding of NO3- and NO2- distribution at rest and indicate that acute BR supplementation increases [NO3-] and [NO2-] in human skin interstitial fluid.

Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women.

A reduction in exercise efficiency with aging limits daily living activities. We examined whether 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) increased exercise efficiency and voluntary achievement of interval walking training (IWT) in older women. Ten women [65 ± 3(SD) yr] who had performed IWT for >12 mo and were currently performing IWT participated in this study. The study was conducted in a placebo-controlled, double-blind crossover design. All subjects underwent two trials for 7 days each in which they performed IWT with ALA+SFC (100 and 115 mg/day, respectively) or placebo supplement intake (CNT), intermittently with a 2-wk washout period. Before and after each trial, subjects underwent a graded cycling test at 27.0 °C atmospheric temperature and 50% relative humidity, and oxygen consumption rate, carbon dioxide production rate, and lactate concentration in plasma were measured. Furthermore, for the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. We found that, in the ALA+SFC trial, oxygen consumption rate and carbon dioxide production rate during graded cycling decreased by 12% (P < 0.001) and 11% (P = 0.001) at every workload, respectively, accompanied by a 16% reduction in lactate concentration in plasma (P < 0.001), although all remained unchanged in the CNT trial (P > 0.2). All of the reductions were significantly greater in the ALA+SFC than the CNT trial (P < 0.05). Furthermore, the training days, impulse, and time at fast walking were 42% (P = 0.028), 102% (P = 0.027), and 69% (P = 0.039) higher during the ALA+SFC than the CNT intake period, respectively. Thus ALA+SFC supplementation augmented exercise efficiency and thereby improved IWT achievement in older women.