Strength training increases walking tolerance in intermittent claudication patients: randomized trial

Objective: To analyse the effects of strength training (ST) in walking capacity in patients with intermittent claudication (IC) compared with walking training (WT) effects. Methods. Thirty patients with IC were randomized into ST and WT. Both groups trained twice a week for 12 weeks at the same rate of perceived exertion. ST consisted of three sets of 10 repetitions of whole body exercises. WT consisted of 15 bouts of 2-minute walking. Before and after the training program walking capacity, peak VO(2), VO(2) at the first stage of treadmill test, ankle brachial index, ischemic window, and knee extension strength were measured. Results: ST improved initial claudication distance (358 +/- 224 vs 504 +/- 276 meters; P < .01), total walking distance (618 +/- 282 to 775 +/- 334 meters; P < .01), VO(2), at the first stage of treadmill test (9.7 +/- 2.6 vs 8.1 +/- 1.7 mL . kg(-1) . minute; P < .01), ischemic window (0.81 +/- 1.16 vs 0.43 +/- 0.47 mm Hg minute meters(-1); P = .04), and knee extension strength (19 +/- 9 vs 21 +/- 8 kg and 21 +/- 9 vs 23 +/- 9; P < .01). Strength increases correlated with the increase in initial claudication distance (r = 0.64; P = .01.) and with the decrease ill VO(2) measured at the first stage of the treadmill test (r = -0.52; P = .04 and r = -0.55; P = .03). Adaptations following ST were similar to the ones observed after WT; however, patients reported lower pain during ST than WT (P < .01). Conclusion: ST improves functional limitation similarly to WT but it produces lower pain, suggesting that this type of exercise could be useful and should be considered in patients with IC. (J Vase Surg 2010;51:89-95.)

Pain threshold is achieved at intensity above anaerobic threshold in patients with intermittent claudication

PURPOSE: Walking training is considered as the first treatment option for patients with peripheral arterial disease and intermittent claudication (IC). Walking exercise has been prescribed for these patients by relative intensity of peak oxygen uptake (VO(2)peak), ranging from 40% to 70% VO(2)peak, or pain threshold (PT). However, the relationship between these methods and anaerobic threshold (AT), which is considered one of the best metabolic markers for establishing training intensity, has not been analyzed. Thus, the aim of this study was to compare, in IC patients, the physiological responses at exercise intensities usually prescribed for training (% VO(2) peak or % PT) with the ones observed at AT. METHODS: Thirty-three IC patients performed maximal graded cardiopulmonary treadmill test to assess exercise tolerance. During the test, heart rate (HR), VO(2), and systolic blood pressure were measured and responses were analyzed at the following: 40% of VO(2)peak; 70% of VO(2)peak; AT; and PT. RESULTS: Heart rate and VO(2) at 40% and 70% of VO(2)peak were lower than those at AT (HR: -13 +/- 9% and -3 +/- 8%, P < .01, respectively; VO(2): -52 +/- 12% and -13 +/- 15%, P < .01, respectively). Conversely, HR and VO(2) at PT were slightly higher than those at AT (HR: +3 +/- 8%, P < .01; VO(2): + 6 +/- 15%, P = .04). None of the patients achieved the respiratory compensation point. CONCLUSION: Prescribing exercise for IC patients between 40% and 70% of VO(2)peak will induce a lower stimulus than that at AT, whereas prescribing exercise at PT will result in a stimulus above AT. Thus, prescribing exercise training for IC patients on the basis of PT will probably produce a greater metabolic stimulus, promoting better cardiovascular benefits.

Physiological and perceived exertion responses at intermittent critical power and intermittent maximal lactate steady state

Okuno, NM, Perandini, LAB, Bishop, D, Simoes, HG, Pereira, G, Berthoin, S, Kokubun, E, and Nakamura, FY. Physiological and perceived exertion responses at intermittent critical power and intermittent maximal lactate steady state. J Strength Cond Res 25(7): 2053-2058, 2011-The aim of this study was to compare the power outputs of the intermittent critical power (CPi) with the intermittent maximal lactate steady state (MLSSi) and to compare the physiological and perceptual responses exercising at CPi and MLSSi. Ten subjects performed intermittent trials on a cycle ergometer to determine CPi and MLSSi using 30: 30 seconds of effort and pause. The oxygen uptake ((V) over dotO(2)), heart rate (HR), blood lactate concentration ([Lac]), and rating of perceived exertion (RPE) responses were compared during 30-minute cycling at CPi and MLSSi. The CPi (267 6 45 W) was similar to MLSSi (254 6 39 W), and they were correlated (r = 0.88; p<0.05). The (V) over dotO(2) and HR responses stabilized throughout exercising at CPi (2.52 +/- 0.52 L.min(-1); 156 +/- 8 b.min(-1)) and MLSSi (2.41 +/- 0.32 L.min(-1); 152 +/- 10 b.min(-1)). These physiological variables were similar between conditions. However, the [Lac] and RPE were higher from the middle to the end of exercise duration at CPi ([Lac] = 6.9 +/- 2.6 mM; RPE = 17.1 +/- 2.1 a.u.) compared to MLSSi ([Lac] = 5.1 +/- 0.9 mM; RPE = 15.7 +/- 1.8 a.u.). Therefore, CPi intensity determined from 30: 30 seconds of effort and rest periods on a cycle ergometer is equivalent to the MLSSi, and there is a physiological steady state throughout both exercise intensities, although the [Lac] and RPE responses at CPi are higher than at MLSSi. Thus, the CPi and MLSSi may be used as tools for intermittent training evaluation and prescription.

Air trapping: The major factor limiting diaphragm mobility in chronic obstructive pulmonary disease patients

Background and objective: Patients with COPD can have impaired diaphragm mechanics. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. This study evaluated the relationship between pulmonary function and diaphragm mobility, as well as that between respiratory muscle strength and diaphragm mobility, in COPD patients. Methods: COPD patients with pulmonary hyperinflation (n = 54) and healthy subjects (n = 20) were studied. Patients were tested for pulmonary function, maximal respiratory pressures and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein. Results: COPD patients had less diaphragm mobility than did healthy individuals (36.5 +/- 10.9 mm vs 46.3 +/- 9.5 mm, P = 0.001). In COPD patients, diaphragm mobility correlated strongly with pulmonary function parameters that quantify air trapping (RV: r = -0.60, P < 0.001; RV/TLC: r = -0.76, P < 0.001), moderately with airway obstruction (FEV1: r = 0.55, P < 0.001; airway resistance: r = -0.32, P = 0.02) and weakly with pulmonary hyperinflation (TLC: r = -0.28, P = 0.04). No relationship was observed between diaphragm mobility and respiratory muscle strength (maximal inspiratory pressure: r = -0.11, P = 0.43; maximal expiratory pressure: r = 0.03, P = 0.80). Conclusion: The results of this study suggest that the reduction in diaphragm mobility in COPD patients is mainly due to air trapping and is not influenced by respiratory muscle strength or pulmonary hyperinflation.

Hypoxia Inducible Factor-Dependent Regulation of Angiogenesis by Nitro-Fatty Acids

Objective-Nitro-fatty acids (NO(2)-FAs) are emerging as a new class of cell signaling mediators. Because NO(2)-FAs are found in the vascular compartment and their impact on vascularization remains unknown, we aimed to investigate the role of NO(2)-FAs in angiogenesis. Methods and Results-The effects of nitrolinoleic acid and nitrooleic acid were evaluated on migration of endothelial cell (EC) in vitro, EC sprouting ex vivo, and angiogenesis in the chorioallantoic membrane assay in vivo. At 10 mu mol/L, both NO(2)-FAs induced EC migration and the formation of sprouts and promoted angiogenesis in vivo in an NO-dependent manner. In addition, NO(2)-FAs increased intracellular NO concentration, upregulated protein expression of the hypoxia inducible factor-1 alpha (HIF-1 alpha) transcription factor by an NO-mediated mechanism, and induced expression of HIF-1 alpha target genes, such as vascular endothelial growth factor, glucose transporter-1, and adrenomedullin. Compared with typical NO donors such as spermine-NONOate and deta-NONOate, NO(2)-FAs were slightly less potent inducers of EC migration and HIF-1 alpha expression. Short hairpin RNA-mediated knockdown of HIF-1 alpha attenuated the induction of vascular endothelial growth factor mRNA expression and EC migration stimulated by NO(2)-FAs. Conclusion-Our data disclose a novel physiological role for NO(2)-FAs, indicating that these compounds induce angiogenesis in an NO-dependent mechanism via activation of HIF-1 alpha. (Arterioscler Thromb Vasc Biol. 2011;31:1360-1367.)

The Absence of Coronary Calcification Does Not Exclude Obstructive Coronary Artery Disease or the Need for Revascularization in Patients Referred for Conventional Coronary Angiography

Objectives This study was designed to evaluate whether the absence of coronary calcium could rule out >= 50% coronary stenosis or the need for revascularization. Background The latest American Heart Association guidelines suggest that a calcium score (CS) of zero might exclude the need for coronary angiography among symptomatic patients. Methods A substudy was made of the CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors) multicenter trial comparing the diagnostic performance of 64-detector computed tomography to conventional angiography. Patients clinically referred for conventional angiography were asked to undergo a CS scan up to 30 days before. Results In all, 291 patients were included, of whom 214 (73%) were male, and the mean age was 59.3 +/- 10.0 years. A total of 14 (5%) patients had low, 218 (75%) had intermediate, and 59 (20%) had high pre-test probability of obstructive coronary artery disease. The overall prevalence of >= 50% stenosis was 56%. A total of 72 patients had CS = 0, among whom 14 (19%) had at least 1 >= 50% stenosis. The overall sensitivity for CS = 0 to predict the absence of >= 50% stenosis was 45%, specificity was 91%, negative predictive value was 68%, and positive predictive value was 81%. Additionally, revascularization was performed in 9 (12.5%) CS = 0 patients within 30 days of the CS. From a total of 383 vessels without any coronary calcification, 47 (12%) presented with >= 50% stenosis; and from a total of 64 totally occluded vessels, 13 (20%) had no calcium. Conclusions The absence of coronary calcification does not exclude obstructive stenosis or the need for revascularization among patients with high enough suspicion of coronary artery disease to be referred for coronary angiography, in contrast with the published recommendations. Total coronary occlusion frequently occurs in the absence of any detectable calcification. (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors [CORE-64]; NCT00738218) (J Am Coll Cardiol 2010;55:627-34) (C) 2010 by the American College of Cardiology Foundation

Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia

Purpose Dasatinib is a BCR-ABL inhibitor, 325-fold more potent than imatinib against unmutated BCR-ABL in vitro. Phase II studies have demonstrated efficacy and safety with dasatinib 70 mg twice daily in chronic-phase (CP) chronic myelogenous leukemia (CML) after imatinib treatment failure. In phase I, responses occurred with once-daily administration despite only intermittent BCR-ABL inhibition. Once-daily treatment resulted in less toxicity, suggesting that toxicity results from continuous inhibition of unintended targets. Here, a dose-and schedule-optimization study is reported. Patients and Methods In this open-label phase III trial, 670 patients with imatinib-resistant or -intolerant CP-CML were randomly assigned 1: 1: 1: 1 between four dasatinib treatment groups: 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. Results With minimum follow-up of 6 months (median treatment duration, 8 months; range, = 1 to 15 months), marked and comparable hematologic (complete, 86% to 92%) and cytogenetic (major, 54% to 59%; complete, 41% to 45%) response rates were observed across the four groups. Time to and duration of cytogenetic response were similar, as was progression-free survival (8% to 11% of patients experienced disease progression or died). Compared with the approved 70-mg twice-daily regimen, dasatinib 100 mg once daily resulted in significantly lower rates of pleural effusion (all grades, 7% v 16%; P = .024) and grade 3 to 4 thrombocytopenia (22% v 37%; P = .004), and fewer patients required dose interruption (51% v 68%), reduction (30% v 55%), or discontinuation (16% v 23%). Conclusion Dasatinib 100 mg once daily retains the efficacy of 70 mg twice daily with less toxicity. Intermittent target inhibition with tyrosine kinase inhibitors may preserve efficacy and reduce adverse events.

Abatacept Improves Health-Related Quality of Life, Pain, Sleep Quality, and Daily Participation in Subjects With Juvenile Idiopathic Arthritis

Objective. To assess health-related quality of life (HRQOL) in abatacept-treated children/adolescents with juvenile idiopathic arthritis (JIA). Methods. In this phase III, double-blind, placebo-controlled trial, subjects with active polyarticular course JIA and an inadequate response/intolerance to >= 1 disease-modifying antirheumatic drug (including biologics) received abatacept 10 mg/kg plus methotrexate (MTX) during the 4-month open-label period (period A). Subjects achieving the American College of Rheumatology Pediatric 30 criteria for improvement (defined ""responders"") were randomized to abatacept or placebo (plus MTX) in the 6-month double-blind withdrawal period (period B). HRQOL assessments included 15 Child Health Questionnaire (CHQ) health concepts plus the physical (PhS) and psychosocial summary scores (PsS), pain (100-mm visual analog scale), the Children`s Sleep Habits Questionnaire, and a daily activity participation questionnaire. Results. A total of 190 subjects from period A and 122 from period B were eligible for analysis. In period A, there were substantial improvements across all of the CHQ domains (greatest improvement was in pain/discomfort) and the PhS (8.3 units) and PsS (4.3 units) with abatacept. At the end of period B, abatacept-treated subjects had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement patterns were seen with pain and sleep. For participation in daily activities, an additional 2.6 school days/month and 2.3 parents` usual activity days/month were gained in period A responders with abatacept, and further gains were made in period B (1.9 versus 0.9 [P = 0.033] and 0.2 versus -1.3 [P = 0.109] school days/month and parents` usual activity days/month, respectively, in abatacept-versus placebo-treated subjects). Conclusion. Improvements in HRQOL were observed with abatacept, providing real-life tangible benefits to children with JIA and their parents/caregivers.

Skeletal Microstructural Abnormalities in Postmenopausal Women With Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is associated with osteoporosis and fragility fractures. The objectives of this study were to assess static and dynamic indices of cancellous and cortical bone structure in postmenopausal women with COPD. Twenty women with COPD who had not received chronic oral glucocorticoids underwent bone biopsies after double tetracycline labeling. Biopsies were analyzed by histomorphometry and mu CT and compared with age-matched controls. Distribution of the patients according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was: Type I (15%), Type II (40%), Type III (30%), and Type IV (15%). Mean (+/-SD) cancellous bone volume (15.20 +/- 5.91 versus 21.34 +/- 5.53%, p = .01), trabecular number (1.31 +/- 0.26 versus 1.77 +/- 0.51/mm, p = .003), and trabecular thickness (141 +/- 23 versus 174 +/- 36 mu m, p = .006) were lower in patients than in controls. Connectivity density was lower in COPD (5.56 +/- 2.78 versus 7.94 +/- 3.08 mu m, p = .04), and correlated negatively with smoking (r = -0.67; p = .0005). Trabecular separation (785 +/- 183 versus 614 +/- 136 mu m, p = .01) and cortical porosity (4.11 +/- 1.02 versus 2.32 +/- 0.94 voids/mm(2); p < .0001) were higher in COPD while cortical width (458 +/- 214 versus 762 +/- 240 mu m; p < .0001) was lower. Dynamic parameters showed significantly lower mineral apposition rate in COPD (0.56 +/- 0.16 versus 0.66 +/- 0.12 mu m/day; p = .01). Patients with more severe disease, GOLD III and IV, presented lower bone formation rate than GOLDI and II (0.028 +/- 0.009 versus 0.016 +/- 0.011 mu m(3)/mu m(2)/day;p = 04). This is the first evaluation of bone microstructure and remodeling in COPD. The skeletal abnormalities seen in cancellous and cortical bone provide an explanation for the high prevalence of vertebral fractures in this disease. (C) 2010 American Society for Bone and Mineral Research.

Prevalence of Metabolic Syndrome in Patients With Intermittent Claudication and its Correlation With the Segment of Arterial Obstruction

The metabolic syndrome (MetS) is associated with increased cardiovascular morbidity and mortality. Intermittent claudication reflects the presence of peripheral arterial disease (PAD). The aim of this study is to determine the prevalence of the MetS in claudicants and its correlation with age, gender, localization of arterial obstruction, and symptomatic coronary disease. Patients (n = 170) with intermittent claudication were studied. The mean age was 65 years (33-89). Metabolic syndrome was diagnosed in 98 patients (57.6%). The mean age of patients with MetS was 63.5 years compared with 67.0 years for patients without MetS (P = .027). Considering patients aged >= 65 years, MetS was present in 46 (48.9%) individuals and in 52 (68.4%) patients younger than 65 years (P = .011). Metabolic syndrome must be actively searched for in claudicant patients.

Potassium in Hemorrhagic Shock: A Potential Marker of Tissue Hypoxia

Background: This study was designed to evaluate serum potassium level variation in a porcine model of hemorrhagic shock ( HS). Methods: Eight pigs were studied in a controlled hemorrhage model of HS. Blood withdrawal began at a 50 mL/min to 70 mL/min rate, adjusted to reach a mean arterial pressure ( MAP) level of 60 mm Hg in 10 minutes. When MAP reached 60 mm Hg, the blood withdrawal rate was adjusted to maintain a MAP decrease rate of 10 mm Hg every 2 minutes to 4 minutes. Arterial and mixed venous blood samples were collected at MAP levels of 60 mm Hg, 50 mm Hg, 40 mm Hg, 30 mm Hg, 20 mm Hg, and 10 mm Hg and analyzed for oxygen saturation, PO(2), PCO(2), potassium, lactate, bicarbonate, hemoglobin, pH, and standard base excess. Results: Significant increase in serum potassium occurred early in all animals. The rate of rise in serum potassium and its levels accompanied the hemodynamic deterioration. Hyperkalemia ( K >5 mmol/L) incidence was 12.5% at 60 mm Hg and 50 mm Hg, 62.5% at 40 mm Hg, 87.5% at 30 mm Hg, and 100% at 20 mm Hg. Strong correlations were found between potassium levels and lactate ( R = 0.82), SvO(2) ( R = 0.87), Delta pH ( R = 0.83), and Delta PCO(2) ( R = 0.82). Conclusions: Serum potassium increase accompanies the onset of HS. The rise in serum potassium was directly related to the hemodynamic deterioration of HS and strongly correlated with markers of tissue hypoxia.

Chronic obstructive pulmonary disease in Brazil: mortality and hospitalization trends and rates, 1996-2008

SETTING: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death among adults in Brazil. OBJECTIVE: To evaluate the mortality and hospitalisation trends in Brazil caused by COPD during the period 1996-2008. DESIGN: We used the health official statistics system to obtain data about mortality (1996-2008) and morbidity (1998-2008) due to COPD and all respiratory diseases (tuberculosis: codes A15-16; lung cancer: code C34, and all diseases coded from J40 to 47 in the 10th Revision of the International Classification of Diseases) as the underlying cause, in persons aged 45-74 years. We used the Joinpoint Regression Program log-linear model using Poisson regression that creates a Monte Carlo permutation test to identify points where trend lines change significantly in magnitude/direction to verify peaks and trends. RESULTS: The annual per cent change in age-adjusted death rates due to COPD declined by 2.7% in men (95%CI -3.6 to -1.8) and -2.0% (95%CI -2.9 to -1.0) in women; and due to all respiratory causes it declined by -1.7% (95%CI 2.4 to -1.0) in men and -1.1% (95%CI -1.8 to -0.3) in women. Although hospitalisation rates for COPD are declining, the hospital admission fatality rate increased in both sexes. CONCLUSION: COPD is still a leading cause of mortality in Brazil despite the observed decline in the mortality/hospitalisation rates for both sexes.

Effects of carbohydrate supplementation on competitive runners undergoing overload training followed by a session of intermittent exercise

This study evaluated the effects of a micro cycle of overload training (1st-8th day) on metabolic and hormonal responses in male runners with or without carbohydrate supplementation and investigated the cumulative effects of this period on a session of intermittent high-intensity running and maximum-performance-test (9th day). The participants were 24 male runners divided into two groups, receiving 61% of their energy intake as CHO (carbohydrate-group) and 54% in the control-group (CON). The testosterone was higher for the CHO than the CON group after the overload training (694.0 +/- A 54.6 vs. CON 610.8 +/- A 47.9 pmol/l). On the ninth day participants performed 10 x 800 m at mean 3 km velocity. An all-out 1000 m running was performed before and after the 10 x 800 m. Before, during, and after this protocol, the runners received solution containing CHO or the CON equivalent. The performance on 800 m series did not differ in either group between the first and last series of 800 m, but for the all-out 1000 m test the performance decrement was lower for CHO group (5.3 +/- A 1.0 vs. 10.6 +/- A 1.3%). The cortisol concentrations were lower in the CHO group in relation to CON group (22.4 +/- A 0.9 vs. 27.6 +/- A 1.4 pmol/l) and the IGF1/IGFBP3 ratio increased 12.7% in the CHO group. During recovery, blood glucose concentrations remained higher in the CHO group in comparison with the CON group. It was concluded that CHO supplementation possibly attenuated the suppression of the hypothalamic-pituitary-gonadal axis and resulted in less catabolic stress, and thus improved running performance.

Test-retest reliability of isokinetic strength and endurance tests in patients with intermittent claudication

The objective was to determine the reliability of isokinetic strength and endurance testing in the ankle joints of patients with intermittent claudication. Twenty-three patients with peripheral artery disease (PAD) and symptoms of intermittent claudication participated in the study. Isokinetic strength and endurance testing of the ankle joint were performed in symptomatic and asymptomatic legs on 3 separate days. Intraclass coefficient correlation of peak torque (PT) and total work (TW) ranged from 0.77 to 0.92 and 0.89 to 0.96, respectively. PT and TW increased significantly and similarly in both legs from day 1 to day 2 (PT: +42 +/- 84% in the symptomatic leg and +33 +/- 51% in the asymptomatic leg, p < 0.05;TW: +38 +/- 26% in the symptomatic leg and +26 +/- 50% in the asymptomatic leg, p < 0.05). In conclusion, isokinetic strength and endurance testing in the ankle joints of patients with PAD presents reliability coefficients ranging from 0.77 to 0.96. However, strength and endurance increased between the first and the other test sessions performed on separate days, suggesting that two test sessions are necessary for the accurate evaluation of strength and endurance in patients with PAD.

Periodic limb movements during sleep and restless legs syndrome in patients with ASIA A spinal cord injury

Objective: To establish the occurrence of Periodic Leg Movements (PLM) and Restless Legs Syndrome (RLS) in Spinal Cord Injury (SCI) subjects. Methods: In this study, twenty four patients were submitted to a full night polysomnography and were assessed with Epworth Sleepiness Scale and an adapted form of International Restless Legs Syndrome Scale Rating Scale (IRLS Rating Scale). Control Group (CG) was composed of 16 subjects, 50% of each sex, age: 24.38 +/- 4 years old. Spinal Cord Injury Group (SCIG) was composed of 8 subjects (29 +/- 5 years old) with a complete SCI (ASIA A) of about three and a half years of duration, 100% males. Results: 100% of SCIG had RLS compared to 17% in CG ( p < 0.0001). SCIG had 18.11 +/- 20.07 of PLM index while CG had 5.96 +/- 11.93 (p = 0.01). Arousals related to PLM were recorded in CG and SCIG. There was a positive moderate correlation between RLS and age (r = 0.5; p = 0.01), RLS and PLM (r = 0.49; p = 0.01), adapted IRLS Rating Scale and PLM index (r = 0.64; p = 0.03) and also a negative moderate correlation between Epworth Sleepiness Scale and PLM index (r = -0.4; p = 0.04) in both groups. Conclusion: RLS and PLM are common findings in SCI patients with a complete injury. (C) 2010 Elsevier B.V. All rights reserved.