Folic Acid Supplementation Improves Vascular Function in Professional Dancers With Endothelial Dysfunction

Objective To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. Design Prospective cross-sectional study. Setting Academic institution in the Midwestern United States. Subjects Twenty-two professional ballet dancers volunteered for this study. Main Outcome Measures Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flow-induced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of Results Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (P\u3c .0001). Conclusions This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention

Association Between the Female Athlete Triad and Endothelial Dysfunction in Dancers

Objective: To determine the prevalence of the 3 components of the female athlete triad [disordered eating, menstrual dysfunction, low bone mineral density (BMD)] and their relationships with brachial artery flow-mediated dilation in professional dancers. Design: Prospective study. Setting: Academic institution in the Midwest. Participants: Twenty-two professional ballet dancers volunteered for this study. Interventions: The prevalence of the female athlete triad and its relationship to endothelial dysfunction. Main Outcome Measures: Subjects completed questionnaires to assess disordered eating and menstrual status/history. They also completed a 3-day food record and wore an accelerometer for 3 days to determine energy availability. Serum baseline thyrotropin, prolactin, and hormonal concentrations were obtained. Bone mineral density and body composition were measured with a GE Lunar Prodigy dual-energy X-ray absorptiometry. Endothelial function was determined as flow-mediated vasodilation measured by high-frequency ultrasound in the brachial artery. An increase in brachial diameter Results: Seventeen dancers (77%) had evidence of low/negative energy availability. Thirty-two percent had disordered eating (EDE-Q score). Thirty-six percent had menstrual dysfunction and 14% were currently using hormone contraception. Twenty-three percent had evidence of low bone density (Z-score \u3c -1.0). Sixty-four percent had abnormal brachial artery flow-mediated dilation ( Conclusions: Endothelial dysfunction was correlated with reduced BMD, menstrual dysfunction, and low serum estrogen. These findings may have profound implications for cardiovascular and bone health in professional women dancers

Impaired Hyperemic Response to Exercise Post Stroke

Individuals with chronic stroke have reduced perfusion of the paretic lower limb at rest; however, the hyperemic response to graded muscle contractions in this patient population has not been examined. This study quantified blood flow to the paretic and non-paretic lower limbs of subjects with chronic stroke after submaximal contractions of the knee extensor muscles and correlated those measures with limb function and activity. Ten subjects with chronic stroke and ten controls had blood flow through the superficial femoral artery quantified with ultrasonography before and immediately after 10 second contractions of the knee extensor muscles at 20, 40, 60, and 80% of the maximal voluntary contraction (MVC) of the test limb. Blood flow to the paretic and non-paretic limb of stroke subjects was significantly reduced at all load levels compared to control subjects even after normalization to lean muscle mass. Of variables measured, increased blood flow after an 80% MVC was the single best predictor of paretic limb strength, the symmetry of strength between the paretic and non-paretic limbs, coordination of the paretic limb, and physical activity. The impaired hemodynamic response to high intensity contractions was a better predictor of lower limb function than resting perfusion measures. Stroke-dependent weakness and atrophy of the paretic limb do not explain the reduced hyperemic response to muscle contraction alone as the response is similarly reduced in the non-paretic limb when compared to controls. These data may suggest a role for perfusion therapies to optimize rehabilitation post stroke

Two Weeks of Ischemic Conditioning Improves Walking Speed and Reduces Neuromuscular Fatigability in Chronic Stroke Survivors

This pilot study examined whether ischemic conditioning (IC), a noninvasive, cost-effective, and easy-to-administer intervention, could improve gait speed and paretic leg muscle function in stroke survivors. We hypothesized that 2 wk of IC training would increase self-selected walking speed, increase paretic muscle strength, and reduce neuromuscular fatigability in chronic stroke survivors. Twenty-two chronic stroke survivors received either IC or IC Sham on their paretic leg every other day for 2 wk (7 total sessions). IC involved 5-min bouts of ischemia, repeated five times, using a cuff inflated to 225 mmHg on the paretic thigh. For IC Sham, the cuff inflation pressure was 10 mmHg. Self-selected walking speed was assessed using the 10-m walk test, and paretic leg knee extensor strength and fatigability were assessed using a Biodex dynamometer. Self-selected walking speed increased in the IC group (0.86 ± 0.21 m/s pretest vs. 1.04 ± 0.22 m/s posttest, means ± SD; P\u3c 0.001) but not in the IC Sham group (0.92 ± 0.47 m/s pretest vs. 0.96 ± 0.46 m/s posttest; P= 0.25). Paretic leg maximum voluntary contractions were unchanged in both groups (103 ± 57 N·m pre-IC vs. 109 ± 65 N·m post-IC; 103 ± 59 N·m pre-IC Sham vs. 108 ± 67 N·m post-IC Sham; P = 0.81); however, participants in the IC group maintained a submaximal isometric contraction longer than participants in the IC Sham group (278 ± 163 s pre-IC vs. 496 ± 313 s post-IC, P = 0.004; 397 ± 203 s pre-IC Sham vs. 355 ± 195 s post-IC Sham; P = 0.46). The results from this pilot study thus indicate that IC training has the potential to improve walking speed and paretic muscle fatigue resistance poststroke

Prediction of immediate ventricular arrhythmias after coronary artery ligation

AbstractObjectives. Our aim was to test the hypothesis that increased beat to beat morphologic variations in the body surface electrocardiogram (ECG) are associated with fragmented diastolic electrical activity that appears after coronary artery ligation and to correlate the appearance of spontaneous ventricular fibrillation after coronary ligation with the magnitude of the ECG beat to beat variability.Background. Unstable and variably delayed electrical activation precedes the development of ventricular fibrillation in dogs with acute ischemia. Detection of these highly variable low amplitude signals from the body surface is currently impossible. We have developed a system designed to measure the degree of beat to beat variability of the ECG.Methods. With high fidelity electrocardiography, subtle beat to beat ECG morphologic variations were detected in epicardial and body surface electrograms and quantified as the variance of the ECG voltage at specific points of the cardiac cycle. The ratio of the variance at the QRS offset to that of the QRS onset (beat to beat variability index) was then calculated.Results. Ventricular fibrillation developed in 12 of 27 dogs after left anterior descending coronary artery ligation. In 7 of the 12 dogs it occurred immediately (<15 min) after ligation; in the other 5 it developed late (15 min) after ligation. Dogs with subsequently immediate ventricular fibrillation had a significantly higher beat to beat variability index than that of dogs with late or no ventricular fibrillation both before coronary ligation (4.7 ± 1.4 vs. 1.1 ± 0.2 and 0.8 ± 0.1, respectively, p < 0.001) and after ligation (6.4 ± 2.6, 1.0 ± 0.6 and 1.2 ± 0.6, respectively, p < 0.001). In dogs that developed ventricular fibrillation immediately after coronary ligation, the arrhythmia was preceded by fragmented diastolic electrical activity on the epicardial electrogram and a simultaneous increase in the beat to beat morphologic variability of the terminal portion of the body surface ECG QRS complex.Conclusions. Beat to beat QRS offset morphologic variations appear to be increased before and further increased after coronary artery ligation in dogs that develop ventricular fibrillation immediately after ligation. Increased beat to beat variability index may be associated with the presence of electrophysiologic instability and can predict early ventricular fibrillation

Ischemic Conditioning Increases Strength and Volitional Activation of Paretic Muscle in Chronic Stroke: A Pilot Study

7siIschemic conditioning (IC) on the arm or leg has emerged as an intervention to improve strength and performance in healthy populations, but the effects on neurologic populations are unknown. The purpose of this study was to quantify the effects of a single session of IC on knee extensor strength and muscle activation in chronic stroke survivors. Maximal knee extensor torque measurements and surface EMG were quantified in 10 chronic stroke survivors (>1 year post-stroke) with hemiparesis before and after a single session of IC or Sham on the paretic leg. IC consisted of five minutes of compression with a proximal thigh cuff (inflation pressure = 225 mmHg for IC or 25 mmHg for Sham) followed by five minutes of rest. This was repeated five times. Maximal knee extensor strength, EMG magnitude, and motor unit firing behavior were measured before and immediately after IC or Sham. IC increased paretic leg strength by 10.6plus minus8.5 Nm while no difference was observed in the Sham group (change in Sham = 1.3plus minus2.9 Nm; p = 0.001 IC vs. Sham). IC-induced increases in strength were accompanied by a 31plus minus15% increase in the magnitude of muscle EMG during maximal contractions and a 5% decrease in motor unit recruitment thresholds during sub-maximal contractions. Individuals who had the most asymmetry in strength between their paretic and non-paretic legs had the largest increases in strength (r2= 0.54). This study provides evidence that a single session of IC can increase strength through improved muscle activation in chronic stroke survivors.openembargoed_20190204Hyngstrom, Allison S; Murphy, Spencer A; Nguyen, Jennifer; Schmit, Brian D; Negro, Francesco; Gutterman, David D; Durand, Matthew JHyngstrom, Allison S; Murphy, Spencer A; Nguyen, Jennifer; Schmit, Brian D; Negro, Francesco; Gutterman, David D; Durand, Matthew

Mechanisms of Vascular Dysfunction in COPD and Effects of a Novel Soluble Epoxide Hydrolase Inhibitor in Smokers.

BACKGROUND: Smoking and COPD are risk factors for cardiovascular disease, and the pathogenesis may involve endothelial dysfunction. We tested the hypothesis that endothelium-derived epoxyeicosatrienoic acid (EET)-mediated endothelial function is impaired in patients with COPD and that a novel soluble epoxide hydrolase inhibitor, GSK2256294, attenuates EET-mediated endothelial dysfunction in human resistance vessels both in vitro and in vivo. METHODS: Endogenous and stimulated endothelial release of EETs was assessed in 12 patients with COPD, 11 overweight smokers, and two matched control groups, using forearm plethysmography with intraarterial infusions of fluconazole, bradykinin, and the combination. The effects of GSK2256294 on EET-mediated vasodilation in human resistance arteries were assessed in vitro and in vivo in a phase I clinical trial in healthy overweight smokers. RESULTS: Compared with control groups, there was reduced vasodilation with bradykinin (P = .005), a blunted effect of fluconazole on bradykinin-induced vasodilation (P = .03), and a trend toward reduced basal EET/dihydroxyepoxyeicosatrienoic acid ratio in patients with COPD (P = .08). A similar pattern was observed in overweight smokers. In vitro, 10 μM GSK2256294 increased 11,12-EET-mediated vasodilation compared with vehicle (90% ± 4.2% vs 72.6% ± 6.2% maximal dilatation) and shifted the bradykinin half-maximal effective concentration (EC50) (-8.33 ± 0.172 logM vs -8.10 ± 0.118 logM; P = .001 for EC50). In vivo, 18 mg GSK2256294 improved the maximum bradykinin response from 338% ± 46% before a dose to 566% ± 110% after a single dose (P = .02) and to 503% ± 123% after a chronic dose (P = .003). CONCLUSIONS: GSK2256294 attenuates smoking-related EET-mediated endothelial dysfunction, suggesting potential therapeutic benefits in patients with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01762774; URL: www.clinicaltrials.gov.This work was supported by GSK [SEH114068] and Innovate UK (ERICA Consortium 10037625), the Wellcome Trust grant numbers 100780/Z/12/Z, and WT103782AIA awarded to LY, and DEN respectively; the Raymond and Beverley Sackler fellowship awarded to LY; National Institute for Health Research funding awarded to IBW, and JC in the Cambridge Comprehensive Biomedical Research, and the British Heart Foundation grant numbers CH/0 9/002, and RG66885 RCZA/008 awarded to DEN, and IBW. JLG and ZA are funded by the Medical Research Council (Medical Research Council Lipid Profiling and Signalling, MC UP A90 1006 & Lipid Dynamics and Regulation, MC PC 130 30)

In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs

Comment in Lowering the High Cost of Cancer Drugs--III. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--I. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--IV. [Mayo Clin Proc. 2016] In Reply--Lowering the High Cost of Cancer Drugs. [Mayo Clin Proc. 2016] US oncologists call for government regulation to curb drug price rises. [BMJ. 2015