Association Between Hemodynamic Profile, Physical Capacity and Quality of Life in Pulmonary Hypertension

Background: No studies have described and evaluated the association between hemodynamics, physical limitations and quality of life in patients with pulmonary hypertension (PH) without concomitant cardiovascular or respiratory disease. Objective: To describe the hemodynamic profile, quality of life and physical capacity of patients with PH from groups I and IV and to study the association between these outcomes. Methods: Cross-sectional study of patients with PH from clinical groups I and IV and functional classes II and III undergoing the following assessments: hemodynamics, exercise tolerance and quality of life. Results: This study assessed 20 patients with a mean age of 46.8 ± 14.3 years. They had pulmonary capillary wedge pressure of 10.5 ± 3.7 mm Hg, 6-minute walk distance test (6MWDT) of 463 ± 78 m, oxygen consumption at peak exercise of 12.9 ± 4.3 mLO2.kg-1.min-1 and scores of quality of life domains < 60%. There were associations between cardiac index (CI) and ventilatory equivalent for CO2 (r=-0.59, p <0.01), IC and ventilatory equivalent for oxygen (r=-0.49, p<0.05), right atrial pressure (RAP) and 'general health perception' domain (r=-0.61, p<0.01), RAP and 6MWTD (r=-0.49, p<0.05), pulmonary vascular resistance (PVR) and 'physical functioning' domain (r=-0.56, p<0.01), PVR and 6MWTD (r=-0.49, p<0.05) and PVR index and physical capacity (r=-0.51, p<0.01). Conclusion: Patients with PH from groups I and IV and functional classes II and III exhibit a reduction in physical capacity and in the physical and mental components of quality of life. The hemodynamic variables CI, diastolic pulmonary arterial pressure, RAP, PVR and PVR index are associated with exercise tolerance and quality of life domains.

Replacement therapy for iron deficiency improves exercise capacity and quality of life in patients with cyanotic congenital heart disease and/or the Eisenmenger syndrome

La teràpia suplementària de ferro millora la capacitat d’exercici i la qualitat de vida en malalts amb una cardiopatia congènita cianòtica i/ o síndrome d’Eisenmenger El dèficit de ferro és una troballa comú en la cardiopatia congènita cianòtica, i pot ser la causa d’una reducció en la capacitat d’exercici. Actualment, està indicada la reposició dels dipòsits de ferro en aquest grup de malalts, éssent les evidències científiques escasses. En el present treball investiguem la seguretat i eficàcia del tractament amb ferro en malalts amb una cardiopatia congènita cianòtica. Per tal motiu, vint-i-cinc malalts amb una cardiopatia congenita cianòtica i dèficit de ferro van ser inclosos de forma prospectiva entre Agost del 2008 i Gener del 2009. El tractament utilitzat fou fumarat ferròs oral, fins a una dosi màxima de 200 mg tres vegades al dia. En l’anàlisi basal i als tres mesos de seguiment es va utilitzar el test de qualitat de vida “CAMPHOR”, el test de la marxa dels 6 minuts i la prova d’esforç amb consum d’oxigen. L’edat mitja fou 39.9+/-10.9 anys, 80% dones. Catorze malalts tenien la síndrome d’Eisenmenger, sis una malaltia cianòtica complexa i cinc circulació de Fontan. Cap d’ells va haver d'interrompre el tractament degut a efectes adversos. Després de tres mesos de tractament, l’hemoglobina (19.0+/-2.9g/dL a 20.4+/-2.7g/dL, p&0.001), ferritina (13.3+/-4.7mug/L a 54.1+/-24.2mug/L, p&0.001) i saturació de transferrina (17.8+/-9.6% a 34.8+/-23.4%, p&0.001) van augmentar significativament. També hi va haver una millora significativa en la puntuació del test de qualitat de vida (20.7+/-10.9 a 16.2+/-10.4, p=0.001) i el test de la marxa (371.7+/-84.7m a 402.8.0+/-74.9m, p=0.001). No es van evidenciar canvis significatius en els valors de consum d’oxigen (40.7+/-9.2% a 43.8+/-12.4%, p=0.15). En definitiva, la teràpia suplementària amb ferro en els malats amb una cardiopatia congènita cianòtica i dèficit de ferro és segura i millora la qualitat de vida i la capacitat funcional. En aquest grup de malalts, per tant, és aconsellable identificar el dèficit de ferro i restaurar-ne els seus dipòsits.

Cytotoxic T cells deficient in both functional fas ligand and perforin show residual cytolytic activity yet lose their capacity to induce lethal acute graft-versus-host disease.

Graft-versus-host disease (GVHD) is the main complication after allogeneic bone marrow transplantation. Although the tissue damage and subsequent patient mortality are clearly dependent on T lymphocytes present in the grafted inoculum, the lethal effector molecules are unknown. Here, we show that acute lethal GVHD, induced by the transfer of splenocytes from C57BL/6 mice into sensitive BALB/c recipients, is dependent on both perforin and Fas ligand (FasL)-mediated lytic pathways. When spleen cells from mutant mice lacking both effector molecules were transferred to sublethally irradiated allogeneic recipients, mice survived. Delayed mortality was observed with grafted cells deficient in only one lytic mediator. In contrast, protection from lethal acute GVHD in resistant mice was exclusively perforin dependent. Perforin-FasL-deficient T cells failed to lyse most target cells in vitro. However, they still efficiently killed tumor necrosis factor alpha-sensitive fibroblasts, demonstrating that cytotoxic T cells possess a third lytic pathway.

Stressing schizotypy: The modulating role of stress-relieving behaviours and intellectual capacity on functional hemispheric asymmetry.

Relative cognitive impairments are common along the schizophrenia spectrum reflecting potential psychopathological markers. Yet stress, a vulnerability marker in schizophrenia (including its spectrum), is likewise related to cognitive impairments. We investigated whether one such cognitive marker (attenuated functional hemispheric asymmetry) during stressful life periods might be linked to individuals' schizotypal features or rather to individuals' stress-related experiences and behaviours. A total of 58 students performed a left hemisphere dominant (lateralised lexical decisions) and right hemisphere dominant (sex decisions on composite faces) task. In order to account for individual differences in stress sensitivity we separated participants into groups of high or low cognitive reserve according to their average current marks. In addition, participants filled in questionnaires on schizotypy (short O-LIFE), perceived stress, stress response, and a newly adapted questionnaire that enquired about potential stress compensation behaviour (elevated substance use). The most important finding was that enhanced substance use and cognitive disorganisation contributed to a right and left hemisphere shift in language dominance, respectively. We discuss that (i) former reports on right hemisphere shifts in language dominance with positive schizotypy might be explained by an associated higher substance use and (ii) cognitive disorganisation relates to unstable cognitive functioning that depend on individuals' life circumstances, contributing to published reports on inconsistent laterality-schizotypy relationships.

Effects of bisoprolol fumarate on left ventricular size, function, and exercise capacity in patients with heart failure: analysis with magnetic resonance myocardial tagging.

BACKGROUND: Recent data suggest that beta-blockers can be beneficial in subgroups of patients with chronic heart failure (CHF). For metoprolol and carvedilol, an increase in ejection fraction has been shown and favorable effects on the myocardial remodeling process have been reported in some studies. We examined the effects of bisoprolol fumarate on exercise capacity and left ventricular volume with magnetic resonance imaging (MRI) and applied a novel high-resolution MRI tagging technique to determine myocardial rotation and relaxation velocity. METHODS: Twenty-eight patients (mean age, 57 +/- 11 years; mean ejection fraction, 26 +/- 6%) were randomized to bisoprolol fumarate (n = 13) or to placebo therapy (n = 15). The dosage of the drugs was titrated to match that of the the Cardiac Insufficiency Bisoprolol Study protocol. Hemodynamic and gas exchange responses to exercise, MRI measurements of left ventricular end-systolic and end-diastolic volumes and ejection fraction, and left ventricular rotation and relaxation velocities were measured before the administration of the drug and 6 and 12 months later. RESULTS: After 1 year, heart rate was reduced in the bisoprolol fumarate group both at rest (81 +/- 12 before therapy versus 61 +/- 11 after therapy; P <.01) and peak exercise (144 +/- 20 before therapy versus 127 +/- 17 after therapy; P <.01), which indicated a reduction in sympathetic drive. No differences were observed in heart rate responses in the placebo group. No differences were observed within or between groups in peak oxygen uptake, although work rate achieved was higher (117.9 +/- 36 watts versus 146.1 +/- 33 watts; P <.05) and exercise time tended to be higher (9.1 +/- 1.7 minutes versus 11.4 +/- 2.8 minutes; P =.06) in the bisoprolol fumarate group. A trend for a reduction in left ventricular end-diastolic volume (-54 mL) and left ventricular end-systolic volume (-62 mL) in the bisoprolol fumarate group occurred after 1 year. Ejection fraction was higher in the bisoprolol fumarate group (25.0 +/- 7 versus 36.2 +/- 9%; P <.05), and the placebo group remained unchanged. Most changes in volume and ejection fraction occurred during the latter 6 months of treatment. With myocardial tagging, insignificant reductions in left ventricular rotation velocity were observed in both groups, whereas relaxation velocity was reduced only after bisoprolol fumarate therapy (by 39%; P <.05). CONCLUSION: One year of bisoprolol fumarate therapy resulted in an improvement in exercise capacity, showed trends for reductions in end-diastolic and end-systolic volumes, increased ejection fraction, and significantly reduced relaxation velocity. Although these results generally confirm the beneficial effects of beta-blockade in patients with chronic heart failure, they show differential effects on systolic and diastolic function.

Functional changes of human quadriceps muscle injured by eccentric exercise

The present study evaluated functional changes of quadriceps muscle after injury induced by eccentric exercise. Maximal isometric torque of quadriceps and the surface electromyography (root mean square, RMS, and median frequency, MDF) of the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles were examined before, immediately after and during the first 7 days after injury. Serum creatine kinase (CK) levels and magnetic resonance imaging (MRI) were used to identify muscle injury. The subject was used as her own control and percent refers to pre-injury data. Experiments were carried out with a sedentary 23-year-old female. Injury was induced by 4 bouts of 15 maximal isokinetic eccentric contractions (angular velocity of 5º/s; range of motion from 40º to 110º of knee flexion). The isometric torque of the quadriceps (knee at 90º flexion) decreased 52% immediately after eccentric exercise and recovered on the 5th day. The highest reduction of RMS occurred on the 2nd day after injury in both VL (63%) and VMO (66%) and only VL recovered to the pre-injury level on the 7th day. Immediately after injury, the MDF decreased by 5 and 3% (VMO and VL, respectively) and recovered one day later. Serum CK levels increased by 109% on the 2nd day and were still increased by 32% on the 7th day. MRI showed large areas of injury especially in the deep region of quadriceps. In conclusion, eccentric exercise decreased the isometric torque and electromyographic signals of quadriceps muscle, which were recovered in one week, despite the muscle regeneration signals.

Functional and morphological effects of resistance exercise on disuse-induced skeletal muscle atrophy

Abstract The reduction of skeletal muscle loss in pathological states, such as muscle disuse, has considerable effects in terms of rehabilitation and quality of life. Since there is no currently effective and safe treatment available for skeletal muscle atrophy, the search for new alternatives is necessary. Resistance exercise (RE) seems to be an important tool in the treatment of disuse-induced skeletal muscle atrophy by promoting positive functional (strength and power) and structural (hypertrophy and phenotypic changes) adaptive responses. Human and animal studies using different types of resistance exercise (flywheel, vascular occlusion, dynamic, isometric, and eccentric) have obtained results of great importance. However, since RE is a complex phenomenon, lack of strict control of its variables (volume, frequency, intensity, muscle action, rest intervals) limits the interpretation of the impact of the manipulation on skeletal muscle remodeling and function under disuse. The aim of this review is to critically describe the functional and morphological role of resistance exercise in disuse-induced skeletal muscle atrophy with emphasis on the principles of training.

Intensity and physiological responses to the 6-minute walk test in middle-aged and older adults: a comparison with cardiopulmonary exercise testing

The 6-minute walk test (6MWT) is a simple field test that is widely used in clinical settings to assess functional exercise capacity. However, studies with healthy subjects are scarce. We hypothesized that the 6MWT might be useful to assess exercise capacity in healthy subjects. The purpose of this study was to evaluate 6MWT intensity in middle-aged and older adults, as well as to develop a simple equation to predict oxygen uptake ( V ˙ O 2 ) from the 6-min walk distance (6MWD). Eighty-six participants, 40 men and 46 women, 40-74 years of age and with a mean body mass index of 28±6 kg/m2, performed the 6MWT according to American Thoracic Society guidelines. Physiological responses were evaluated during the 6MWT using a K4b2 Cosmed telemetry gas analyzer. On a different occasion, the subjects performed ramp protocol cardiopulmonary exercise testing (CPET) on a treadmill. Peak V ˙ O 2 in the 6MWT corresponded to 78±13% of the peak V ˙ O 2 during CPET, and the maximum heart rate corresponded to 80±23% of that obtained in CPET. Peak V ˙ O 2 in CPET was adequately predicted by the 6MWD by a linear regression equation: V ˙ O 2 mL·min-1·kg-1 = -2.863 + (0.0563×6MWDm) (R2=0.76). The 6MWT represents a moderate-to-high intensity activity in middle-aged and older adults and proved to be useful for predicting cardiorespiratory fitness in the present study. Our results suggest that the 6MWT may also be useful in asymptomatic individuals, and its use in walk-based conditioning programs should be encouraged.

Commercial spices and industrial ingredients: evaluation of antioxidant capacity and flavonoids content for functional foods development

The aim of this work was to evaluate spices and industrial ingredients for the development of functional foods with high phenolic contents and antioxidant capacity. Basil, bay, chives, onion, oregano, parsley, rosemary, turmeric and powdered industrial ingredients (β-carotene, green tea extract, lutein, lycopene and olive extract) had their in vitro antioxidant capacity evaluated by means of the Folin-Ciocalteu reducing capacity and DPPH scavenging ability. Flavonoids identification and quantification were performed by High Performance Liquid Chromatography (HPLC). The results showed that spices presented a large variation in flavonoids content and in vitro antioxidant capacity, according to kind, brand and batches. Oregano had the highest antioxidant capacity and parsley had the highest flavonoid content. The industrial ingredient with the highest antioxidant capacity was green tea extract, which presented a high content of epigalocatechin gallate. Olive extract also showed a high antioxidant activity and it was a good source of chlorogenic acid. This study suggests that oregano, parsley, olive and green tea extract have an excellent potential for the development of functional foods rich in flavonoids as antioxidant, as long as the variability between batches/brands is controlled.

The effects of upper extremity functional electrically stimulated (FES) exercise training on upper limb function in individuals with tetraplegia

Functional Electrically Stimulated (FES) ami cycle ergometry is a relatively new technique for exercise in individuals with impairments of the upper limbs. The purpose of this study was to determine the effects of 12 weeks of FES arm cycle ergometry on upper limb function and cardiovascular fitness in individuals with tetraplegia. F!ve subjects (4M/1F; mean age 43.8 ± 15.4 years) with a spinal cord injury of the cervical spine (C3- C7; ASIA B-D) participated in 12 weeks of3 times per week FES arm cycle ergometry training. Exercise performance measures (time to fatigue, distance to fatigue, work rate) were taken at baseline, 6 weeks, and following 12 weeks of training. Cardiovascular measures (MAP, resting HR, average and peak HR during exercise, cardiovascular efficiency) and self reported upper limb function (as determined by the CUE, sf-QIF, SCI-SET questionnaires) were taken at baseline and following 12 weeks of training. Increases were found in time to fatigue (84.4%), distance to fatigue (111.7%), and work rate (51.3%). These changes were non-significant. There was a significant decrease in MAP (91.1 ± 13.9 vs. 87.7 ± 14.7 mmHg) following 12 weeks ofFES arm cycle ergometry. There was no significant change in resting HR or average and peak HR during exercise. Cardiovascular efficiency showed an increase following the 12 weeks ofFES training (142.9%), which was non-significant. There were no significant changes in the measures of upper limb function and spasticity. Overall, FES arm cycle ergometry is an effective method of cardiovascular exercise for individuals with tetraplegia, as evidenced by a significant decrease in MAP, however it is unclear whether 12 weeks of thrice weekly FES arm cycle ergometry may effectively improve upper limb function in all individuals with a cervical SCI.

Canadian Society for Exercise Physiology Position Paper: Resistance Training in Children and Adolescents

Many position stands and review papers have refuted the myths associated with resistance training (RT) in children and adolescents. With proper training methods, RT for children and adolescents can be relatively safe and improve overall health. The objective of this position paper and review is to highlight research and provide recommendations in aspects of RT that have not been extensively reported in the pediatric literature. In addition to the well-documented increases in muscular strength and endurance, RT has been used to improve function in pediatric patients with cystic fibrosis, cerebral palsy and burn victims. Increases in children’s muscular strength have been attributed primarily to neurological adaptations due to the disproportionately higher increase in muscle strength than in muscle size. Although most studies using anthropometric measures have not shown significant muscle hypertrophy in children, more sensitive measures such as magnetic resonance imaging and ultrasound have suggested hypertrophy may occur. There is no minimum age for RT for children. However the training and instruction must be appropriate for children and adolescents involving a proper warm-up, cool-down and an appropriate choice of exercises. It is recommended that low-to-moderate intensity resistance should be utilized 2-3 times per week on non-consecutive days, with 1-2 sets initially, progressing to 4 sets of 8-15 repetitions for 8-12 exercises. These exercises can include more advanced movements such as Olympic style lifting, plyometrics and balance training, which can enhance strength, power, co-ordination and balance. However specific guidelines for these more advanced techniques need to be established for youth. In conclusion, a RT program that is within a child’s or adolescent’s capacity, involves gradual progression under qualified instruction and supervision with appropriately sized equipment can involve more advanced or intense RT exercises which can lead to functional (i.e. muscular strength, endurance, power, balance and co-ordination) and health benefits.

Switching curve control of functional electrical stimulation assisted rowing exercise in paraplegia

An indoor rowing machine has been modified for functional electrical stimulation (FES) assisted rowing exercise in paraplegia. To perform the rowing manoeuvre successfully, however, the voluntarily controlled upper body movements must be co-ordinated with the movements of the electrically stimulated paralysed legs. To achieve such co-ordination, an automatic FES controller was developed that employs two levels of hierarchy. At the upper level, a finite state controller identifies the state or phase of the rowing cycle and activates the appropriate lower-level controller, in which electrical stimulation to the paralysed leg muscles is applied with reference to switching curves representing the desired seat velocity as a function of the seat position. In a pilot study, the hierarchical control of FES rowing was shown to be intuitive, reliable and easy to use. Compared with open-loop control of stimulation, all three variants of the closed-loop switching curve controllers used less muscle stimulation per rowing cycle (73% of the open-loop control on average). Further, the closed-loop controller that used switching curves derived from normal rowing kinematics used the lowest muscle stimulation (65% of the open-loop control) and was the most convenient to use for the client.

Using gap-crossing capacity to evaluate functional connectivity of two Atlantic rainforest birds and their response to fragmentation

One of the main consequences of habitat loss and fragmentation is the increase in patch isolation and the consequent decrease in landscape connectivity. In this context, species persistence depends on their responses to this new landscape configuration, particularly on their capacity to move through the interhabitat matrix. Here, we aimed first to determine gap-crossing probabilities related to different gap widths for two forest birds (Thamnophilus caerulescens, Thamnophilidae, and Basileuterus culicivorus, Parulidae) from the Brazilian Atlantic rainforest. These values were defined with a playback technique and then used in analyses based on graph theory to determine functional connections among forest patches. Both species were capable of crossing forest gaps between patches, and these movements were related to gap width. The probability of crossing 40 m gaps was 50% for both species. This probability falls to 10% when the gaps are 60 m (for B. culicivorus) or 80 m (for T caerulescens). Actually, birds responded to stimulation about two times more distant inside forest trials (control) than in gap-crossing trials. Models that included gap-crossing capacity improved the explanatory power of species abundance variation in comparison to strictly structural models based merely on patch area and distance measurements. These results highlighted that even very simple functional connectivity measurements related to gap-crossing capacity can improve the understanding of the effect of habitat fragmentation on bird occurrence and abundance.

Brainstem oxytocinergic modulation of heart rate control in rats: effects of hypertension and exercise training

Oxytocinergic brainstem projections participate in the autonomic control of the circulation. We investigated the effects of hypertension and training on cardiovascular parameters after oxytocin (OT) receptor blockade within the nucleus tractus solitarii (NTS) and NTS OT and OT receptor expression. Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were trained (55% of maximal exercise capacity) or kept sedentary for 3 months and chronically instrumented (NTS and arterial cannulae). Mean arterial blood pressure (MAP) and heart rate (HR) were measured at rest and during an acute bout of exercise after NTS pretreatment with vehicle or OT antagonist (20 pmol of OT antagonist (200 nl of vehicle)-1). Oxytocin and OT receptor were quantified (35S-oligonucleotide probes, in situ hybridization) in other groups of rats. The SHR exhibited high MAP and HR (P < 0.05). Exercise training improved treadmill performance and reduced basal HR (on average -11%) in both groups, but did not change basal MAP. Blockade of NTS OT receptor increased exercise tachycardia only in trained groups, with a larger effect on trained WKY rats (+31 +/- 9 versus +12 +/- 3 beats min-1 in the trained SHR). Hypertension specifically reduced NTS OT receptor mRNA density (-46% versus sedentary WKY rats, P < 0.05); training did not change OT receptor density, but significantly increased OT mRNA expression (+2.5-fold in trained WKY rats and +15% in trained SHR). Concurrent hypertension- and training-induced plastic (peptide/receptor changes) and functional adjustments (HR changes) of oxytocinergic control support both the elevated basal HR in the SHR group and the slowing of the heart rate (rest and exercise) observed in trained WKY rats and SHR.