Muscle oxygen utilization and ventilatory parameters during exercise in people with cystic fibrosis: Role of HbA.

Introduction: Glycated hemoglobin can interfere with oxygen delivery and CO removal during exercise. Additionally, pancreatic insufficiency increases oxidative stress and exacerbates exercise intolerance in people with cystic fibrosis (PwCF). This investigation sought to test the hypotheses that elevated Hemoglobin A (HbA) can negatively affect exercise parameters in PwCF and that reductions in oxidative stress can improve tissue oxygenation in individuals with elevated HbA.

Exercise Intolerance in Cystic Fibrosis: Importance of Skeletal Muscle.

Purpose: Exercise intolerance, evaluated by O2 consumption, predicts mortality in cystic fibrosis (CF). People with CF exhibit skeletal muscle dysfunctions that may contribute to an imbalance between O2 delivery and utilization. Sildenafil, a phosphodiesterase type 5 inhibitor, increases blood flow and improves O2 consumption, although the exact mechanisms in CF have yet to be elucidated.

Sildenafil improves exercise capacity in patients with cystic fibrosis: a proof-of-concept clinical trial.

Background: Exercise intolerance is a common phenotype observed in patients with cystic fibrosis (CF). Treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, has previously been shown to improve exercise capacity (VO peak) in other patient populations. Thus, the present study sought to determine the acute and subacute effects of sildenafil on exercise capacity in patients with CF.

Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress.

Oxidative stress and vascular endothelial dysfunction are established characteristics of cystic fibrosis (CF). Oxidative stress may contribute to vascular dysfunction via inhibition of nitric oxide (NO) bioavailability. .

Acute Tetrahydrobiopterin Improves Endothelial Function in Patients With COPD.

Background: Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH would improve endothelial function in patients with COPD via an increase in NO bioavailability.

A single high-fat meal provokes pathological erythrocyte remodeling and increases myeloperoxidase levels: implications for acute coronary syndrome.

High-fat meal (HFM) consumption can produce acute lipemia and trigger myocardial infarction in patients with atherosclerosis, but the mechanisms are poorly understood. Erythrocytes (red blood cells, RBCs) intimately interact with inflammatory cells and blood vessels and play a complex role in regulating vascular function. Chronic high-fat feeding in mice induces pathological RBC remodeling, suggesting a novel link between HFM, RBCs, and vascular dysfunction.

Blood flow regulation and oxidative stress during submaximal cycling exercise in patients with cystic fibrosis.

Background: The impact of blood flow regulation and oxidative stress during exercise in cystic fibrosis (CF) has yet to be investigated.

Methods: A maximal graded exercise test was conducted to determine exercise capacity (VO peak) and peak workload in 14 pediatric patients with mild CF (age 14±3y, FEV 93±16 % predicted) and 14 demographically-matched controls. On a separate visit, participants performed submaximal cycling up to 60% of peak workload where brachial artery blood velocity was determined using Doppler ultrasound.

A single bout of maximal exercise improves lung function in patients with cystic fibrosis.

Background: Responses to a single bout of exercise may provide critical information for maximizing improvements in pulmonary function following exercise training in cystic fibrosis (CF). We sought to determine if acute maximal exercise improves pulmonary function in patients with CF.

Methods: Thirty-three patients with CF completed a comprehensive assessment of pulmonary function to determine forced vital capacity (FVC), forced expiratory volume in one second (FEV), and lung clearance index (LCI) prior to and immediately following maximal aerobic exercise on a cycle ergometer.

BH4 improves postprandial endothelial function after a high-fat meal in men and postmenopausal women.

Objective: The timing and duration of menopause is important when evaluating the risk for cardiovascular disease in postmenopausal women, likely related in part to nitric oxide (NO) bioavailability. The flow-mediated dilation (FMD) test is a noninvasive assessment of NO bioavailability in humans, and tetrahydrobiopterin (BH4) is essential for NO synthesis. A high-fat meal (HFM) has been used to increase lipemia and reduce NO bioavailability.

Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test.

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a pathological condition characterized mainly by a disruption in the balance between vasodilator and vasoconstrictor substances and is proposed to play an important role in the development of atherosclerotic cardiovascular disease. Therefore, a precise evaluation of endothelial function in humans represents an important tool that could help better understand the etiology of multiple cardio-centric pathologies.

Evidence of microvascular dysfunction in patients with cystic fibrosis.

Cystic fibrosis (CF) is a genetic, multisystemic disorder with broad clinical manifestations apart from the well-characterized pulmonary dysfunction. Recent findings have described impairment in conduit vessel function in patients with CF; however, whether microvascular function is affected in this population has yet to be elucidated. Using laser-Doppler imaging, we evaluated microvascular function through postocclusive reactive hyperemia (PORH), local thermal hyperemia (LTH), and iontophoresis with acetylcholine (ACh).

Assessments of endothelial function and arterial stiffness are reproducible in patients with COPD.

Background: Elevated cardiovascular disease risk is observed in patients with COPD. Non-invasive assessments of endothelial dysfunction and arterial stiffness have recently emerged to provide mechanistic insight into cardiovascular disease risk in COPD; however, the reproducibility of endothelial function and arterial stiffness has yet to be investigated in this patient population.

Objectives: This study sought to examine the within-day and between-day reproducibility of endothelial function and arterial stiffness in patients with COPD.

Oxygen uptake kinetics and exercise capacity in children with cystic fibrosis.

Exercise capacity, an objective measure of exercise intolerance, is known to predict quality of life and mortality in cystic fibrosis (CF). The mechanisms for exercise intolerance in patients with cystic fibrosis (CF), however, have yet to be fully elucidated. Accordingly, this study sought to investigate oxygen uptake kinetics and the impact of fat-free mass (FFM) on exercise capacity in young patients with CF.

Skeletal muscle oxidative capacity in patients with cystic fibrosis.

What is the central question of this study? Do patients with cystic fibrosis have reduced skeletal muscle oxidative capacity, measured with near-infrared spectroscopy, compared with demographically matched control subjects? What is the main finding and is its importance? Patients with cystic fibrosis have impairments in skeletal muscle oxidative capacity. This reduced skeletal muscle oxidative capacity not only appears to be accelerated by age, but it may also contribute to exercise intolerance in patients with cystic fibrosis. Exercise intolerance predicts mortality in patients with cystic fibrosis (CF); however, the mechanisms have yet to be elucidated fully.

Association beween resting heart rate, shear and flow-mediated dilation in healthy adults.

Preclinical data have demonstrated that heart rate (HR) can directly impact vascular endothelial function, in part, through a shear-stress mechanism. This study sought to explore, in humans, the associations between resting heart rate and both shear and endothelial function assessed by flow-mediated dilation (FMD). The brachial artery FMD test was performed in 31 apparently healthy volunteers.

Epithelial sodium channel inhibition by amiloride on blood pressure and cardiovascular disease risk in young prehypertensives.

Overactivity of the epithelial sodium channel (ENaC) is considered to be one mechanism underlying obesity-related blood pressure (BP) elevation. In an open-labeled, nonplacebo-controlled clinical trial (Clinicaltrials.gov: NCT-01308983), the authors aimed to comprehensively evaluate the effects of amiloride monotherapy, an ENaC blocker, on BP and cardiovascular risk in young adults with prehypertension (n=17).