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1.
Acute resveratrol supplementation in coronary artery disease: towards patient stratification.
Diaz, M, Avila, A, Degens, H, Coeckelberghs, E, Vanhees, L, Cornelissen, V, Azzawi, M
Scandinavian cardiovascular journal : SCJ. 2020;(1):14-19
Abstract
Objective: Resveratrol (RV) is a polyphenol with antioxidant, anti-inflammatory and cardio-protective properties. Our objective was to investigate whether acute supplementation with high doses of RV would improve flow-mediated dilation (FMD) and oxygen consumption (VO2) kinetics in older coronary artery disease (CAD) patients. Design: We employed a placebo-controlled, single-blind, crossover design in which ten participants (aged 66.6 ± 7.8 years) received either RV or placebo (330 mg, 3× day-1) during three consecutive days plus additional 330 mg in the morning of the fourth day with a seven-day wash-out period in-between. On the fourth day, FMD of the brachial artery and VO2 on-kinetics were determined. Results: RV improved FMD in patients who had undergone coronary artery bypass grafting (CABG; -1.4 vs. 5.0%; p = .004), but not in those who had undergone percutaneous coronary intervention (PCI; 4.2 vs. -0.2%; NS). Conclusion: Acute high dose supplementation with RV improved FMD in patients after CABG surgery but impaired FMD in patients who underwent PCI. The revascularization method-related differential effects of RV may be due to its direct effects on endothelial-dependent dilator responses. Our findings have important implications for personalized treatment and stratification of older CAD patients.
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2.
Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes.
Mackenzie, R, Maxwell, N, Castle, P, Elliott, B, Brickley, G, Watt, P
The Journal of clinical endocrinology and metabolism. 2012;(4):E546-55
Abstract
CONTEXT Hypoxia and muscle contraction stimulate glucose transport activity in vitro. Exercise and hypoxia have additive effects on insulin sensitivity in type 2 diabetics (T2D). OBJECTIVE The objective of the study was to examine the effectiveness of intermittent exercise with and without hypoxia on acute- and moderate-term glucose kinetics and insulin sensitivity in T2D. SETTING The study was conducted at a university research center. DESIGN, PARTICIPANTS, AND INTERVENTIONS Eight male T2D patients completed the following: 1) 60 min of continuous exercise at 90% lactate threshold in hypoxia (HyEx60); 2) intermittent exercise at 120% lactate threshold, separated by periods of passive recovery (5:5 min) in hypoxia [Hy5:5; O₂ ∼ 14.7 (0.2)%]; and 3) intermittent exercise (5:5 min) at 120% lactate threshold in normoxia (O₂ ∼ 20.93%). MAIN OUTCOME MEASURES Glucose appearance and glucose disappearance, using an adapted non-steady-state one-compartment model were measured. Homeostasis models of insulin resistance (HOMA(IR)), fasting insulin resistance index (FIRI), and β-cell function were calculated 24 and 48 h after exercise conditions. RESULTS Glucose disappearance increased from baseline (1.85 mg/kg · min⁻¹) compared with 24 h (2.01 min/kg · min⁻¹) after HyEx60 (P = 0.031). No difference was noted for both Hy5:5 (P = 0.064) and normoxia (P = 0.385). Hy5:5 demonstrated improvements in HOMA(IR) from baseline [d 1, 6.20 (0.40)] when comparisons were made with d 2 [4.83 (0.41)] (P = 0.0013). HOMA(IR) and FIRI improved in the 24 h (HOMA(IR), P = 0.002; FIRI, P = 0.003), remaining reduced 48 h after HyEx60 (HOMA(IR), P = 0.028; and FIRI, P = 0.034). CONCLUSION HyEx60 offered the greatest improvements in acute and moderate-term glucose control in T2D. Intermittent exercise stimulated glucose disposal and improved post-exercise insulin resistance, which was enhanced when exercise was combined with hypoxia (Hy5:5). The data suggest a use of hypoxic exercise in treatment of T2D.
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3.
Effect of acute changes in oxygen tension on flow-mediated dilation. Relation to cardivascular risk.
Frøbert, O, Holmager, P, Jensen, KM, Schmidt, EB, Simonsen, U
Scandinavian cardiovascular journal : SCJ. 2008;(1):38-47
Abstract
OBJECTIVE Oxygen-dependent changes in vascular diameters may be detrimental when the endothelium is dysfunctional. DESIGN Endothelial responsiveness was evaluated by brachial ultrasound and flow-mediated/nitroglycerin-mediated dilation (FMD/NMD). FMD/NMD was investigated in males with increased risk of cardiovascular disease (mean age 44+/-2 years, n=10) and matched controls without risk factors (44+/-2 years, n=10). FMD/NMD was assessed during normoxia (21% O2, 79% N2), while inhaling hypoxic gas (12.5% O2, FMDHyp/NMD), and 100% O2 supplementation (FMDO2/NMD). In a second study we addressed the effect of lipid lowering. Twenty persons with cardiovascular risk (mean age 50+/-2 years) were treated with atorvastatin (80 mg/day) and FMD/NMD was measured during normoxia, hypoxia and oxygen supplementation before, after 1 day and 3 months. RESULTS Oxygen supplementation evoked vasoconstriction, while FMDHyp/NMD was reduced compared to FMD/NMD. Atorvastatin significantly lowered total cholesterol, LDL cholesterol, and ADMA after 1 day of treatment, while triglycerides, ApoB and hsCRP were lowered after 3 months. Atorvastatin did not change FMD/NMD irrespective of oxygen tension. CONCLUSION Irrespective of risk factors or atorvastatin, hypoxia reduced endothelial vasodilation while oxygen supplementation evoked vasoconstriction.
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4.
Supplemental oxygen and muscle metabolism in mitochondrial myopathy patients.
Trenell, MI, Sue, CM, Thompson, CH, Kemp, GJ
European journal of applied physiology. 2007;(5):541-7
Abstract
Patients with mitochondrial myopathy (MM) have a reduced capacity to perform exercise due to a reduced oxidative capacity. We undertook this study to determine whether skeletal muscle metabolism could be improved with oxygen therapy in patients with MM. Six patients with MM and six controls, matched for age, gender and physical activity, underwent (31)P-magnetic resonance spectroscopy ((31)P-MRS) examination. (31)P-MR spectra were collected at rest and in series during exercise and recovery whilst breathing normoxic (0.21 O(2)) or hyperoxic (1.0 O(2)) air. At rest, MM showed an elevated [ADP] (18 +/- 3 micromol/l) and pH (7.03 +/- 0.01) in comparison to the control group (12 +/- 1 micromol/l, 7.01 +/- 0.01) (P < 0.05) consistent with mitochondrial dysfunction. Oxygen supplementation did not change resting metabolites in either MM or the control group (P > 0.05). Inferred maximal ATP synthesis rate improved by 33% with oxygen in MM (21 +/- 3 vs. 28 +/- 5 mmol/(l min), P < 0.05) but only improved by 5% in controls (40 +/- 3 vs. 42 +/- 3 mmol/(l min), P > 0.05). We conclude that oxygen therapy is associated with significant improvements in muscle metabolism in patients with MM. These data suggest that patients with MM could benefit from therapies which improve the provision of oxygen.
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5.
Extracellular amino acid changes in patients during reversible cerebral ischaemia.
Kett-White, R, O'Connell, MT, Hutchinson, PJ, Al-Rawi, PG, Gupta, AK, Pickard, JD, Kirkpatrick, PJ
Acta neurochirurgica. Supplement. 2005;:83-8
Abstract
This study investigated the changes in extracellular chemistry during reversible human cerebral ischaemia. Delayed analysis was performed on samples taken from a subgroup of patients during aneurysm surgery previously reported. Frozen microdialysis samples from 14 patients who had all undergone temporary clipping of the ipsilateral internal carotid artery (ICA) were analysed for another 15 amino acids with HPLC and for glycerol with CMA-600. Changes were characterised according to whether cerebral tissue oxygen pressure (PBO2) decreases were brief or prolonged. Brief ICA clipping (maximum duration of 16 minutes) in 11 patients was not associated with changes in amino acids or glycerol. Cerebral ischaemia, defined by a PBO2 decrease below 1.1 kPa for at least 30 minutes during ICA occlusion, occurred in 3 patients. None of whom developed an infarct in the monitored region. This prolonged reversible ischaemia was associated with transient delayed increases in gamma-amino butyric acid (GABA) as well as glutamate and glycerol, each by two-to-three folds. This study demonstrates detectable transient increases in human extracellular glutamate, GABA and glycerol during identified periods of reversible cerebral ischaemia, maximal 30-60 minutes after onset of ischaemia, but not in other amino acids detected by HPLC.
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6.
Oxidative state in platelets and erythrocytes in aging and Alzheimer's disease.
Kawamoto, EM, Munhoz, CD, Glezer, I, Bahia, VS, Caramelli, P, Nitrini, R, Gorjão, R, Curi, R, Scavone, C, Marcourakis, T
Neurobiology of aging. 2005;(6):857-64
Abstract
Several studies have shown involvement of peroxynitrite anion, a potent oxidative agent, in Alzheimer's disease (AD) neuropathology. Herein, we assessed in platelets and erythrocytes of AD patients, age-matched and young adults controls: thiobarbituric acid-reactive substances (TBARS) production; superoxide dismutase (SOD), nitric oxide synthase (NOS) and Na,K-ATPase activities; cyclic GMP (cGMP) content, both basal and after sodium nitroprusside (SNP) stimulation. Aging was associated with an increase in TBARS production and NOS activity, a decrease in basal cGMP content and no change in SOD and Na,K-ATPase activities. AD patients, compared to aged controls, have: increase in TBARS production and in NOS, SOD and Na,K-ATPase activities but no alteration in basal cGMP content. SNP increased cGMP platelets production in all groups. In conclusion, we demonstrated in platelets and erythrocytes a disruption in systemic modulation of oxidative stress in aging and with more intensity in AD.
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7.
Preexercise metabolic alkalosis induced via bicarbonate ingestion accelerates Vo2 kinetics at the onset of a high-power-output exercise in humans.
Zoladz, JA, Szkutnik, Z, Duda, K, Majerczak, J, Korzeniewski, B
Journal of applied physiology (Bethesda, Md. : 1985). 2005;(3):895-904
Abstract
The present study investigated the effect of preexercise metabolic alkalosis on the primary component of oxygen uptake (Vo(2)) kinetics, characterized by tau(1). Seven healthy physically active nonsmoking men, aged 22.4 +/- 1.8 (mean +/- SD) yr, maximum Vo(2) (Vo(2 max)) 50.4 +/- 4 ml.min(-1).kg(-1), performed two bouts of cycling, corresponding to 40 and 87% of Vo(2 max), lasting 6 min each, separated by a 20-min pause, once as a control study and a few days later at approximately 90 min after ingestion of 3 mmol/kg body wt of NaHCO(3). Blood samples for measurements of bicarbonate concentration and hydrogen ion concentration were taken from antecubital vein via catheter. Pulmonary Vo(2) was measured continuously breath by breath. The values of tau(1) were calculated by using six various approaches published in the literature. Preexercise level of bicarbonate concentration after ingestion of NaHCO(3) was significantly elevated (P < 0.01) compared with the control study (28.96 +/- 2.11 vs. 24.84 +/- 1.18 mmol/l; P < 0.01), and [H(+)] was significantly (P < 0.01) reduced (42.79 +/- 3.38 nmol/l vs. 46.44 +/- 3.51 nmol/l). This shift (P < 0.01) was also present during both bouts of exercise. During cycling at 40% of Vo(2 max), no significant effect of the preexercise alkalosis on the magnitude of tau(1) was found. However, during cycling at 87% of Vo(2 max), the tau(1) calculated by all six approaches was significantly (P < 0.05) reduced, compared with the control study. The tau(1) calculated as in Borrani et al. (Borrani F, Candau R, Millet GY, Perrey S, Fuchsloscher J, and Rouillon JD. J Appl Physiol 90: 2212-2220, 2001) was reduced on average by 7.9 +/- 2.6 s, which was significantly different from zero with both the Student's t-test (P = 0.011) and the Wilcoxon's signed-ranks test (P = 0.014).
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8.
Reduced intracellular oxygen radical production in whole blood leukocytes from COPD patients and asymptomatic smokers.
Wehlin, L, Löfdahl, M, Lundahl, J, Sköld, M
Chest. 2005;(4):2051-8
Abstract
RATIONALE AND OBJECTIVES COPD is characterized by irreversible airflow obstruction. It has, however, become clear that COPD also is a systemic disease. In the present study, we sought to investigate its impact on different peripheral leukocyte subpopulations that are recognized as important effector cells in the lung tissue. METHODS We enrolled 20 patients with stable, moderate COPD (FEV1, 33 to 69%). Ten asymptomatic smokers and 10 nonsmokers served as control groups. Flow cytometry and whole blood analysis were used to minimize unwanted ex vivo modulation. Oxidative burst and adhesion molecule mobilization were analyzed on freshly drawn cells and after in vitro activation. MEASUREMENTS AND MAIN RESULTS We found reduced oxidative burst in neutrophils, monocytes, and eosinophils after in vitro stimulation with tumor necrosis factor (TNF) and the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) in both COPD patients and asymptomatic smokers as compared to nonsmoking control subjects. Vascular involvement was determined as increased soluble intercellular adhesion molecule-1 (sICAM-1) in the COPD group. There were no differences in adhesion molecule expression among the three groups. However, in COPD patients who had smoked the same morning prior to blood sampling, we found a reduced ability to mobilize adhesion molecule CD11b after TNF plus fMLP activation in all investigated cell types. "Acute" smoking did not significantly alter respiratory burst measurements. CONCLUSIONS Both COPD patients and asymptomatic smokers have increased levels of sICAM-1 and a reduced intracellular oxidative burst in vitro, indicating a vascular endothelial activation and a possible state of refractoriness in circulating phagocytes in COPD. Although expression and mobilization of adhesion molecules were similar between groups, the acute smoke effect on CD11b points out the value of information on smoking behavior when analyzing function of peripheral inflammatory cells in a smoking population.
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9.
Is tube feeding associated with altered arterial oxygen saturation in stroke patients?
Dutta, D, Bannerjee, M, Chambers, T
Age and ageing. 2004;(5):493-6
Abstract
BACKGROUND Reduced arterial oxygen saturation (SaO(2)) during swallowing, oral feeding and feeding tube placement has been demonstrated in stroke patients. It is not known if tube feeding causes similar episodes of arterial desaturation and whether there is a case for routine pulse oximetry during tube feeding. OBJECTIVE To determine if tube feeding in stroke patients is associated with hypoxia. METHODS We compared ischaemic or haemorrhagic stroke patients who were NG or PEG fed with a control group of age matched non-dysphagic stroke patients who were orally fed. We excluded people already on supplemental oxygen. Pulse oximetry was performed before, during a meal (for 20 min) and for 10 min after and changes from baseline readings determined. RESULTS Data were collected for 20 controls and 18 tube-fed patients. Mean age was 75 years and median time to assessment 14.5 days. The two groups were reasonably matched for age, sex, type of stroke and time to assessment, but differed significantly in the Oxfordshire Community Stroke Project (OCSP) classification and Rankin score. The mean baseline SaO(2) of controls was 96.5% (SD 1.47) and that of the tube-fed group 96.0% (SD 1.46). Reduction in SaO(2) from baseline during and after feeding ranged from 0.35% to 0.78% with no statistically or clinically significant differences between the two groups. CONCLUSIONS No clinically significant reduction in SaO(2) was found in our tube-fed patients as compared to controls. Our study suggests that routine pulse oximetry during tube feeding is not necessary.
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10.
Cerebral hemodynamics and metabolism in adult moyamoya disease: comparison of angiographic collateral circulation.
Piao, R, Oku, N, Kitagawa, K, Imaizumi, M, Matsushita, K, Yoshikawa, T, Takasawa, M, Osaki, Y, Kimura, Y, Kajimoto, K, et al
Annals of nuclear medicine. 2004;(2):115-21
Abstract
PURPOSE The extent of the hemodynamic and metabolic impairments in adult patients with moyamoya disease is still controversial. The aim of the present study was to evaluate the hemodynamic and metabolic status in relation to the development of basal moyamoya vessels (BMVs). METHODS The cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) were measured using PET in ten patients with ischemic adult moyamoya disease (mean age, 36.6 years) and six age-matched normal controls (mean age, 33.3 years). The cerebrovascular reserve (CVR) after acetazolamide (ACZ) loading was also estimated using iodine-123 N-isopropyl-p-iodo amphetamine single photon emission computed tomography (123I-IMP SPECT). RESULTS Based on the angiographic findings, eleven cerebral hemispheres with well-developed BMV (extensive BMV hemispheres) and nine cerebral hemispheres with diminished BMV (diminished BMV hemispheres) were identified. The main routes of collateral circulation in extensive BMV hemispheres were BMVs and leptomeningeal anastomoses. On the other hand, in diminished BMV hemispheres, transdural anastomosis was predominant, and leptomeningeal anastomoses were less developed. In cortices distal to the occluded internal carotid artery, the extensive BMV hemispheres exhibited a significantly lower CBF, CMRO2, CBF/CBV, and CVR (p < 0.05) and a significantly higher CBV and OEF than in diminished BMV hemispheres and controls (p < 0.05). Except for the CBF in the white matter, the mean hemodynamic and metabolic parameters of the diminished BMV hemispheres were not significantly different from those of the controls. CONCLUSION The extensive development of basal moyamoya vessels is a sign of severe hemodynamic impairment in adult patients with ischemic moyamoya disease. The results may not apply to adults with hemorrhagic onset.