Predictive Value of V̇O in Adult Congenital Heart Disease in Comparison with Heart Failure with Reduced Ejection Fraction.

Background: Peak oxygen consumption (V̇O ) is used to predict outcomes and the timing of transplantation in patients with heart failure with reduced ejection fraction (HFrEF); V̇O also has predictive utility in patients with adult congenital heart disease (ACHD). However, the predictive value of a given V̇O in patients with ACHD compared to those with HFrEF, especially after adjustment for age and sex, is not clear.

Methods: To address this, we performed a longitudinal cohort study comparing patients with ACHD to patients with HFrEF.

Preworkout dietary nitrate magnifies training-induced benefits to physical function in late postmenopausal women: a randomized pilot study.

To inform end points for future work, we explored the utility of preworkout (i.e., an acute dose before training) beetroot juice (BRJ) combined with exercise (BRJ + EX) to augment indices of physical function in postmenopausal women compared with exercise only (EX).

Dietary NO does not enhance endothelial dependent cutaneous vascular conductance in older women.

Prior work has yet to determine whether the reduction of dietary nitrate (NO) to NO, via the enterosalivary pathway, may modify cutaneous vascular conductance (CVC) responses to local heating in older women. Changes occurring with the transition to menopause related to hormonal flux, increased adiposity, and/or decreased physical activity may further compound the negative influence of aging on nitric oxide (NO)-dependent CVC. Herein, we characterized changes in NO-dependent CVC following acute ingestion of 140 mL of NO-rich beetroot juice in 24 older women (age: 65 ± 5 y, BMI: 31.

Beetroot juice supplementation and exercise performance: is there more to the story than just nitrate?

This mini-review summarizes the comparative effects of different sources of dietary nitrate (NO), beetroot juice (BRJ) and nitrate salts (NIT), on physiological function and exercise capacity. Our objectives were to determine whether BRJ is superior to NIT in enhancing exercise-related outcomes, and to explore the potential contribution of other putatively beneficial compounds in BRJ beyond NO. We conducted a comparative analysis of recent studies focused on the impact of BRJ versus NIT on submaximal oxygen consumption (VO), endurance performance, adaptations to training, and recovery from muscle-damaging exercise.

The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design.

Background: Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF).

Short-term beetroot juice supplementation improves muscle speed and power but does not reduce blood pressure or oxidative stress in 65-79 y old men and women.

We have previously demonstrated that acute ingestion of inorganic nitrate (NO)-rich beetroot juice (BRJ), a source of nitric oxide (NO) via the NO → nitrite (NO) → NO pathway, can improve muscle speed and power in older individuals. It is not known, however, whether this effect is maintained or perhaps even enhanced with repeated ingestion, or if tolerance develops as with organic nitrates, e.g.

The influence of acute dietary nitrate supplementation on skeletal muscle fatigue and recovery in older women.

Older individuals fatigue more rapidly during, and recover more slowly from, dynamic exercise. Women are particularly vulnerable to these deleterious effects of aging, which increases their risk of falling. We have shown that dietary nitrate (NO ), a source of nitric oxide (NO) via the NO  → nitrite (NO ) → NO pathway, enhances muscle speed and power in older individuals in the non-fatigued state; however, it is unclear if it reduces fatigability and/or improves recoverability in this population.

The influence of acute dietary nitrate supplementation on skeletal muscle fatigue and recovery in older women.

Older individuals fatigue more rapidly during, and recover more slowly from, dynamic exercise. Women are particularly vulnerable to these deleterious effects of aging, which increases their risk of falling. We have shown that dietary nitrate (NO ), a source of nitric oxide (NO) via the NO → nitrite (NO ) → NO pathway, enhances muscle speed and power in older individuals in the non-fatigued state; however, it is unclear if it reduces fatigability and/or improves recoverability in this population.

Klotho: An Emerging Factor With Ergogenic Potential.

Sarcopenia and impaired cardiorespiratory fitness are commonly observed in older individuals and patients with chronic kidney disease (CKD). Declines in skeletal muscle function and aerobic capacity can progress into impaired physical function and inability to perform activities of daily living. Physical function is highly associated with important clinical outcomes such as hospitalization, functional independence, quality of life, and mortality.

Skeletal muscle blood flow during exercise is reduced in a rat model of pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is characterized by exercise intolerance. Muscle blood flow may be reduced during exercise in PAH; however, this has not been directly measured. Therefore, we investigated blood flow during exercise in a rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH).

Initiation of Dialysis Is Associated With Impaired Cardiovascular Functional Capacity.

Background The transition to dialysis period carries a substantial increased cardiovascular risk in patients with chronic kidney disease. Despite this, alterations in cardiovascular functional capacity during this transition are largely unknown. The present study therefore sought to assess ventilatory exercise response measures in patients within 1 year of initiating dialysis.

Skeletal Muscle Contractile Function in Heart Failure With Reduced Ejection Fraction-A Focus on Nitric Oxide.

Despite advances over the past few decades, heart failure with reduced ejection fraction (HFrEF) remains not only a mortal but a disabling disease. Indeed, the New York Heart Association classification of HFrEF severity is based on how much exercise a patient can perform. Moreover, exercise capacity-both aerobic exercise performance and muscle power-are intimately linked with survival in patients with HFrEF.

Nitric oxide and skeletal muscle contractile function.

Nitric oxide (NO) is complex modulator of skeletal muscle contractile function, capable of increasing or decreasing force and power output depending on multiple factors. This review explores the effects and potential mechanisms for modulation of skeletal muscle contractile function by NO, from pharmacological agents in isolated muscle preparations to dietary nitrate supplementation in humans and animals. Pharmacological manipulation in vitro suggests that NO signaling diminishes submaximal isometric force, whereas dietary manipulation in vivo suggest that NO enhances submaximal force.

Dietary Nitrate Supplementation and Exercise-Related Performance.

Over the last decade, there has been a growing interest in the utility of nitrate (NO3) supplementation to improve exercise-related performance. After consumption, dietary NO3 can be reduced to nitric oxide, a free radical gas involved in numerous physiological actions including blood vessel vasodilation, mitochondrial respiration, and skeletal muscle contractile function. Emerging evidence indicates that dietary NO3 supplementation has a small but nevertheless significant beneficial effect on endurance performance through the combined effects of enhanced tissue oxygenation and metabolic efficiency in active skeletal muscle.

Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis.

Background: Previous narrative reviews have concluded that dietary nitrate (NO) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO on various aspects of exercise performance (i.

Dose-Response Effect of Dietary Nitrate on Muscle Contractility and Blood Pressure in Older Subjects: A Pilot Study.

We have recently demonstrated that dietary nitrate, a source of nitric oxide (NO) via the nitrate → nitrite → NO enterosalivary pathway, can improve muscle contractility in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in some, but not all, studies of older individuals. However, the optimal dose for eliciting these beneficial effects is unknown.

Simultaneous Pharmacokinetic Analysis of Nitrate and its Reduced Metabolite, Nitrite, Following Ingestion of Inorganic Nitrate in a Mixed Patient Population.

Purpose: The pharmacokinetic properties of plasma NO and its reduced metabolite, NO, have been separately described, but there has been no reported attempt to simultaneously model their pharmacokinetics following NO ingestion. This report describes development of such a model from retrospective analyses of concentrations largely obtained from primary endpoint efficacy trials.

Methods: Linear and non-linear mixed effects analyses were used to statistically define concentration dependency on time, dose, as well as patient and study variables, and to integrate NO and NO concentrations from studies conducted at different times, locations, patient groups, and several studies in which sample range was limited to a few hours.

Cardiovascular Functional Changes in Chronic Kidney Disease: Integrative Physiology, Pathophysiology and Applications of Cardiopulmonary Exercise Testing.

The development of cardiovascular disease during renal impairment involves striking multi-tiered, multi-dimensional complex alterations encompassing the entire oxygen transport system. Complex interactions between target organ systems involving alterations of the heart, vascular, musculoskeletal and respiratory systems occur in Chronic Kidney Disease (CKD) and collectively contribute to impairment of cardiovascular function. These systemic changes have challenged our diagnostic and therapeutic efforts, particularly given that imaging cardiac structure at rest, rather than ascertainment under the stress of exercise, may not accurately reflect the risk of premature death in CKD.

Potential health effects of dietary nitrate supplementation in aging and chronic degenerative disease.

In the United States, latest projections indicate the number of adults 65 years of age and older is expected to double by 2050. Given that increased oxidative stress is a hallmark of aging, it is understandable that waning nitric oxide and chronic degenerative disease arise in tandem. To this end, translational evidence-based strategies are needed to mitigate the impending toll on personal and public health.