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PubMed2003

Effects of the mammary gland on functional capacities of blood mononuclear leukocyte populations from periparturient cows.

The composition and functional capacity of peripheral blood mononuclear leukocyte populations from dairy cows are altered substantially during the peripartal period. These changes are associated with a heightened susceptibility of the mammary gland to infection. It has been postulated that the metabolic demands associated with lactogenesis may impact negatively leukocyte function during the periparturient period. In the present study, serum immunoglobulin G1 concentration and functional capacities of peripheral blood mononuclear leukocytes from intact (n = 6) and mastectomized (n = 6) periparturient Jersey cows were evaluated and compared. Cell function assessments included lymphocyte proliferation, immunoglobulin M secretion, and interferon-gamma secretion by unstimulated and pokeweed mitogen stimulated mononuclear leukocytes. Data were summarized as mean responses for 5-d periods beginning 21 d prepartum and concluding at 19 d postpartum. The progressive decrease in serum immunoglobulin G in intact but not mastectomized cows before parturition likely was attributable to the selective uptake of this isotype by the mammary gland. Lymphocyte proliferation and secretion of interferon-gamma and polyclonal IgM by mitogen-stimulated leukocytes from intact cows decreased during the 15-d period before calving, reaching a nadir at 0 to 4 d postpartum. From 5 to 19 d postpartum, these functions often were comparable to those observed 2 to 3 wk prepartum. Functions of leukocytes from mastectomized cows did not change during the study period, although they often were of lower magnitude than those of cells from nonlactating cows. These results reconfirm the occurrence of a generalized reduction in blood mononuclear leukocyte function during the periparturient period. They also suggest that the reduction in leukocyte function during the period may be, in part, due to the physiologic demands imposed on the dairy cow by the lactating mammary gland.

Animals↗

PubMed2005

The association between NT-proBNP levels, functional capacity and stage in patients with heart failure.

OBJECTIVE: Amino-terminal probrain natriuretic peptide (NT-proBNP), a biologically inactive derivative of BNP, is clinically more useful owing to its longer half-life, higher plasma concentrations, lesser variation among individuals, and higher in vitro stability. In this regard, NT-proBNP may be a better indicator of the severity of ventricular dysfunction. In this study, the association of NT-proBNP levels with functional capacity and stage of heart failure was explored in patients with CHF. Also, we particularly focused on the presence and significance of neurohormonal activation in the group of patients classified as stage-A according to ACC/AHA guidelines. METHODS AND RESULTS: 64 patients with CHF (31 men, 33 women; mean age 58.26 +/- 10.59 y) and 36 healthy controls (24 men, 12 women; mean age 57.47 +/- 10.83) were included in this study. The New York Heart Association (NYHA) classification system (I, II, III, IV) was used to define the functional capacity; and the stage of the heart failure was based on the ACC/AHA guidelines (A, B, C, D). Healthy female participants had higher NT-proBNP levels compared to their male counterparts (p < 0.001). Left ventricular ejection fraction (LVEF) did not correlate significantly with functional capacity and stage of the disease. CHF patients had higher NT-proBNP compared to controls (p < 0.001). There was a positive correlation between NT-proBNP and functional capacity in patients, and NT-proBNP increased significantly with each increasing class of the disease. Similarly, a positive correlation existed between the stage of heart failure and NT-proBNP levels, which increased significantly with increasing stages of the disease. Patients with NYHA I and stage A disease had higher NT-proBNP levels compared to controls (p = 0.04). CONCLUSIONS: The severity of CHF can be objectively assessed by measuring the circulating levels of NT-proBNP. Even in NYHA I and stage A disease, NT-proBNP levels are higher compared to controls (p = 0.04). NT-proBNP can provide objective information regarding the severity of the disease and also aid in treatment decisions in patients with CHF.

Aged↗

PubMed2006

The value of estimated functional capacity in estimating outcome: results from the NHBLI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study.

OBJECTIVES: Our objective was to determine the prognostic value of estimated metabolic equivalents (METs) based on self-reported functional capacity by the Duke Activity Status Index (DASI) in symptomatic women. BACKGROUND: Functional capacity is an important component affecting the predictive value of exercise testing, yet current guidelines offer limited assistance regarding identification of functional impairment and choice of pharmacologic stress testing. METHODS: A total of 914 women underwent clinically indicated coronary angiography and completed the 12-item DASI questionnaire; a subgroup of 251 women also underwent exercise testing. Cox proportional hazards modeling was used to estimate five-year death or myocardial infarction by DASI scores. In a secondary analysis, additional events included unstable angina, heart failure, or stroke at five years. RESULTS: Average DASI-estimated functional capacity was 5.7 +/- 4.2 METs and, for exercising women, 6.0 +/- 2.6 METs. In the 914 women, event-free survival ranged from 83% to 95% in subgroups with < or =4.7 to >9.9 METs (p = 0.009); 67% of the events occurred in women scoring < or =4.7 METs (p = 0.003). Event rates were similar by exercise and DASI MET values. In women with DASI-estimated METs < or =4.7 (n = 75), ischemia occurred less (39% vs. 64%, p < 0.0001), and exercise testing results were more often indeterminate (<85% predicted maximum heart rate = 37% vs. 6%, p = 0.001) as compared to women achieving >4.7 METs. CONCLUSIONS: Among women with suspected myocardial ischemia, functional impairment estimated by the DASI correlates with indeterminate exercise test results and is associated with an adverse prognosis. Use of the DASI before exercise testing can risk stratify symptomatic women and may improve the identification of higher-risk, functionally impaired subjects that would benefit from pharmacologic stress imaging and targeted risk management.

Adult↗

PubMedDate not supplied

[Motor function and functional capacity in hemiplegia with global aphasia after rehabilitation].

PURPOSE: The influence of global aphasia on the outcome rehabilitation of hemiplegia has been considered in very few case studies. Aim of this study is to evaluate motor function and functional capacities of patients whit hemiplegia and global aphasia after rehabilitation. PATIENTS AND METHODS: A consecutive sample of 54 first-stroke patients was assessed. The mean age of the patients was 64.9. Assessments were made using the Barthel Index, Fugl-Meyer Scale and Standard Language Examination of Basso. RESULTS: At admission 98.1% of the patients showed a complete paresis of the upper limb, while 72.2% provided a complete paresis of the lower limb. After rehabilitation 90.7% of the cases showed a complete paresis of the upper limb while 29.6% maintained the paresis of the lower limb. The lower limb had motriciy in flexor- and extensor synergies, while the upper limb only in flexor-synergies. At admission all patients showed severe or very severe disability. After rehabilitation disability was very severe in 9.2% of the patients, severe in 16.7%, moderate in 38.9% and light in 35.2%. At discharge 33.3% of the patients had a Berthel Index score above 70 while the mean score was 59.2/100. The higher self-sufficiency was detected in the personal hygiene (83% self-sufficient) and walking (61.1%); a lower degree of self-sufficiency was observed in eating, dressing and toileting (100% of the patients needed assistance). The patients aged less than 65 years showed a recovery in the functional capacities better than the level detected in patients older than 65 (p < 0.001). CONCLUSIONS: These results demonstrate that patients whit hemiplegia and global aphasia recovery better functional capacities than motor function after rehabilitation.

Aged↗

PubMed1994

[Body fluid withdrawal with isolated ultrafiltration effects persistent improvement of functional capacity in patients with chronic congestive heart failure. Furosemide does not produce the same result].

In moderate congestive heart failure pulmonary overhydration may be detected at chest X-ray even if therapy is optimized to keep the urinary output normal and to prevent weight gain and dependent edema formation. Removal of overhydration of the lung may help to define its significance. This study was aimed at investigating whether a subclinical accumulation of fluid in the lung interstitium in moderate congestive heart failure interferes with the patient's functional capacity, and whether furosemide is able to promote reabsorption of the excessive fluid. Patients whose digoxin, oral furosemide and ACE-inhibitor therapeutic regimen was kept constant, were randomly allocated to ultrafiltration (8 cases) or iv bolus (mean dose = 248 mg) of supplemental furosemide (8 cases). The amount of body fluid removed with each method approximated 1.600 ml. Functional performance was assessed with cardiopulmonary exercise tests. Soon after fluid withdrawal with either procedure the filling pressures of the two ventricles and body weight were reduced and plasma renin activity, norepinephrine and aldosterone were augmented. After furosemide hormones remained elevated in the subsequent 4 days, and, during this period, patients had positive water metabolism, recovery of the elevated ventricular filling pressures, recurrence of lung congestion without any improvement in functional capacity. In ultrafiltrated patients, renin, norepinephrine and aldosterone fell below control values within the first 48 hours and water metabolism was equilibrated at a new set point (less fluid intake and diuresis without weight gain). Functional capacity in these patients was improved through favorable circulatory and ventilatory adjustments consequent on reabsorption of lung water. This may also have restored the ability of the lung to clear norepinephrine, thus restraining its facilitation of renin release. Improvement persisted at 3 months after the procedure. In congestive heart failure the set point of fluid balance is altered despite oral furosemide; supplemental iv furosemide does not shift the set point, at least in the presence of ACE-inhibition; excessive, although silent, lung water limits the functional capacity of the patient.

Aged↗

PubMed1997

New method and device for assessment of functional capacity of upper extremity with chronic ischemia.

BACKGROUND: The aim of this study is to establish an objective diagnostic method, through which the functional capacity of the upper extremity with chronic ischemia could be best assessed. METHODS: For a 9-year period (1986-1994) 74 patients suffering Arterial Occlusive Disease (AOD) of the upper extremity with chronic ischemia were treated. Fifty five of them (74.3%) were males (an average age of 52.4 years) and 19 females (25.6%), (an average age of 42.5 years). Forty nine of them (66.2%) were in second stage according to the adapted Fontain's classification. An original method and device have been established for the investigation of the abilities of the upper extremity to make repeated movements till they get an intermittent claudication. The apparatus consists of tree modules: a mechanical device, an interface adapter and a microcomputer. RESULTS: During the flexion of the fingers the patient overcomes the resistance of springs which is 1.82 Nm. An Ischemic Fatigue Index (IFI) is calculated--it gives the quantitative value of the functional capacity of the limb. IFI in patients in second stage of Chronic Arterial Ischemia (CAI) is from 0.14 to 0.76 during the diagnostic test and from 0.18 to 1.0 after the operative or drug treatment or Percutaneous Transluminal Angioplasty (PTA). A retrospective analysis shows that in patients who were operated on, the preoperative IFI was less than 0.50. The measurement of Arm-Arm Blood Pressure Index (AABPI) before treatment and after it in some cases shows normal values in spite of the presence of subclavian artery stenoses. The angiographies that were done could not help for the evaluation of the functional capacity of the upper extremities. The presence of pulse in 9 patients (18.4%) does not exclude a presence of occlusion. CONCLUSIONS: IFI is a quantitative indicator for the upper extremity capacity. It shows whether the symptoms are severe enough to justify the surgery. The periodical measurement of IFI is a monitoring of the development of AOD.

Adolescent↗

PubMedDate not supplied

The functional capacity evaluation: measuring maximal work abilities.

Functional capacity evaluation (FCE) is a systematic, comprehensive, objective measurement of an individual's maximal work abilities. This article describes the uses, objectives, and components of FCEs, the various types of FCEs employed, and their advantages and disadvantages.

Accidents, Occupational↗

PubMed2005

Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity.

The monocyte population in blood is considered a possible source of endothelial precursors. Because endothelial-specific receptor tyrosine kinases act as regulators of endothelial cell function, we investigated whether expression of the vascular endothelial growth factor receptor-2 (VEGFR-2) on monocytes is important for their endothelial-like functional capacity. Peripheral-blood monocytes expressing vascular endothelial growth factor receptor-2 (VEGFR-2), or CD14+/VEGFR-2+, were isolated, and their phenotypic, morphologic, and functional capacities were compared with those of monocytes negative for this marker (CD14+/VEGFR-2-). CD14+/VEGFR-2+ cells constituted approximately 2% +/- 0.5% of the total population of monocytes and 0.08% +/- 0.04% of mononuclear cells in blood. CD14+/VEGFR-2+ cells exhibited the potential to differentiate in vitro into cells with endothelial characteristics. The cells were efficiently transduced by a lentiviral vector driving expression of the green fluorescence protein (GFP). Transplantation of GFP-transduced cells into balloon-injured femoral arteries of nude mice significantly contributed to efficient reendothelialization. CD14+/VEGFR-2- did not exhibit any of these characteristics. These data demonstrate that the expression of VEGFR-2 on peripheral blood monocytes is essential for their endothelial-like functional capacity and support the notion of a common precursor for monocytic and endothelial cell lineage. Our results help clarify which subpopulations may restore damaged endothelium and may participate in the maintenance of vascular homeostasis.

Animals↗

PubMed2005

Determinants of functional capacity in patients with chronic heart failure: role of filling pressure and systolic and diastolic function.

BACKGROUND: Previous work suggesting a better correlation of diastolic than systolic function with exercise capacity in heart failure may reflect the relative insensitivity and load-dependence of ejection fraction (EF). We sought the correlation of new and more sensitive methods of quantifying systolic and diastolic function and filling pressure with functional capacity. METHODS: We studied 155 consecutive exercise tests on 95 patients with congestive heart failure (81 male, aged 62 +/- 10 years), who underwent resting 2-dimensional echocardiography and tissue Doppler imaging before and after measurement of maximum oxygen uptake (peak VO2). RESULTS: The resting EF was 31% +/- 10% and a peak VO2 was 13 +/- 5 mL/kg.min; the majority of these patients (80%) had an ischemic cardiomyopathy. Resting EF (r = 0.14, P = .09) correlated poorly with peak VO2 and mean systolic (r = 0.23, P = .004) and diastolic tissue velocities (r = 0.18, P = .02). Peak EF was weakly correlated with the mean systolic (r = 0.18, P = .02) and diastolic velocities (r = 0.16, P < .04). The mean sum of systolic and diastolic velocities in both annuli (r = 0.30, P < .001) and E/Ea ratio (r = -0.31, P < .001) were better correlated with peak VO2 . Prediction of peak VO2 was similar with models based on models of filling pressure (R = 0.61), systolic factors (R = 0.63), and diastolic factors (R = 0.59), although a composite model of filling pressure, systolic and diastolic function was a superior predictor of peak VO2 (R = 0.69; all P < .001). CONCLUSIONS: The reported association of diastolic rather than systolic function with functional capacity may have reflected the limitations of EF. Functional capacity appears related not only to diastolic function, but also to systolic function and filling pressure, and is most closely associated with a combination of these factors.

Aged↗

PubMed2006

Association of socioeconomic status with functional capacity, heart rate recovery, and all-cause mortality.

CONTEXT: Lower socioeconomic status (SES) confers heightened cardiovascular risk and mortality, although the mediating pathways are unclear. OBJECTIVE: To evaluate the extent to which exercise physiologic characteristics account for the association between lower SES and mortality. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 30 043 consecutive patients living in 7 counties in northeast Ohio referred between 1990 and 2002 for symptom-limited stress testing for evaluation of known or suspected coronary artery disease. Follow-up for mortality continued through February 2004. MAIN OUTCOME MEASURES: Estimated functional capacity in metabolic equivalents and heart rate recovery, physiologic characteristics that are determined directly from exercise; testing and all-cause mortality during a median follow-up of 6.5 years. RESULTS: Multivariable models adjusting for demographics, insurance status, smoking status, and clinical confounders demonstrated a strong association between a composite SES score based on census block data and functional capacity (adjusted odds ratio comparing 25th with 75th percentile values, 1.72; 95% confidence interval [CI], 1.56-1.89; P<.001) as well as heart rate recovery (adjusted odds ratio comparing 25th with 75th percentile values, 1.18; 95% CI, 1.07-1.30; P<.001). There were 2174 deaths, with mortality risk increasing from 5% to 10% as SES decreased by quartile (P<.001). Cox proportional hazards models that included all confounding variables except exercise physiologic characteristics demonstrated increased mortality as SES decreased (adjusted hazard ratio comparing 25th with 75th percentile values, 1.32; 95% CI, 1.22-1.42; P<.001). After further adding functional capacity and heart rate recovery, the magnitude of this relationship was reduced (comparing 25th with 75th percentile values; adjusted hazard ratio, 1.17; 95% CI, 1.08-1.26; P<.001), with these variables explaining 47% of the association. CONCLUSIONS: Impaired functional capacity and abnormal heart rate recovery were strongly associated with lower SES and accounted for a major proportion of the correlation between SES and mortality. Efforts to modify these clinical features among patients with low SES may narrow disparities in mortality.

Adult↗

PubMed2003

A single bisphosphonate infusion is associated with improved functional capacity in elderly subjects with primary hyperparathyroidism.

BACKGROUND AND AIMS: Neuromuscular symptoms are frequent features of primary hyperparathyroidism in elderly patients. Whether these symptoms are related to concomitant disorders or to hypercalcemia is of major importance in selecting patients who could benefit by parathyroidectomy. To address this hypothesis, we investigated the effects of transient normalization of calcemia on functional capacity by the administration of a single infusion of the bone resorption inhibitors pamidronate or clodronate. METHODS: Functional capacity was evaluated by the functional independence measure (FIM) in 25 patients aged 87.1+/-0.8 years (means+/-SEM) with primary hyperparathyroidism. Nine patients aged 88.4+/-1.1 with primary hyperparathyroidism, not receiving any bisphosphonate, were used as controls. RESULTS: By inhibiting bone resorption, bisphosphonate administration caused transient normalization of calcemia, associated with improved FIM, at a significantly higher level than in untreated patients (+16.1+/-6.0 vs +4.2+/-3.2%, p<0.05). CONCLUSIONS: If confirmed in a randomized prospective study, these results indicate that a single bisphosphonate infusion, with consecutive transient improvement of functional capacity in relation to plasma calcium normalization, could help in identifying elderly patients who would benefit by parathyroidectomy.

Activities of Daily Living↗

PubMed1994

Functional capacity before and after cardioversion of atrial fibrillation: a controlled study.

OBJECTIVE: To evaluate the effect of cardioversion on peak oxygen consumption (peak VO2) in patients with long-standing atrial fibrillation, to assess the importance of underlying heart disease with respect to the response to exercise, and to relate functional capacity to long-term arrhythmia outcome. DESIGN: Prospective controlled clinical trial. SETTING: Tertiary referral centre. PATIENTS: 63 consecutive patients with chronic atrial fibrillation accepted for treatment with electrical cardioversion. Before cardioversion all patients were treated with digoxin, verapamil, or a combination of both to attain a resting heart rate < or = 100 beats per minute. INTERVENTIONS: Electrical cardioversion. MAIN OUTCOME MEASURES: Peak VO2 measured before and 1 month after electrical cardioversion to compare patients who were in sinus rhythm and those in atrial fibrillation at these times. Maintenance of sinus rhythm for a mean follow up of 19 (7) months. RESULTS: Mean (1SD) peak VO2 in patients in sinus rhythm after 1 month (n = 37) increased from 21.4 (5.8) to 23.7 (6.4) ml/min/kg (+11%, P < 0.05), whereas in patients with a recurrence of atrial fibrillation 1 month after cardioversion (n = 26) peak VO2 was unchanged. In patients who were in sinus rhythm both those with and without underlying heart disease improved, and improvement was not related to functional capacity or left ventricular function before cardioversion. Baseline peak VO2 was not a predictive factor for long-term arrhythmia outcome. CONCLUSION: Restoration of sinus rhythm improved peak VO2 in patients with atrial fibrillation, irrespective of the presence of underlying heart disease. Peak VO2 was not a predictive factor for long-term arrhythmia outcome after cardioversion of atrial fibrillation. These findings suggest that cardioversion is the best method of improving functional capacity in patients with atrial fibrillation, whether or not they have underlying heart disease and whatever their functional state.

Atrial Fibrillation↗

PubMed2003

Composition and functional capacity of blood mononuclear leukocyte populations from neonatal calves on standard and intensified milk replacer diets.

Effects of increased dietary energy and protein on the composition and functional capacities of blood mononuclear leukocyte populations from milk replacer-fed calves were investigated. Holstein bull calves (average age: 4.2 d; n = 19) were assigned randomly to one of two treatment groups. Treatment 1 calves (n = 9) were fed a 20% crude protein, 20% fat milk replacer at a rate of 1.4% body weight of dry matter/d for 8 wk, whereas treatment 2 calves (n = 10) were fed a 30% crude protein, 20% fat milk replacer at a rate of 2.5% body weight of dry matter per day. Composition and functional capacities of mononuclear leukocyte populations from blood samples collected at 4, 18, 32, 46, and 60 d of age were characterized by flow cytometry and ex vivo cell function assays. From 11 to 60 d of age, the mean daily weight gain of treatment 2 calves (1.20 kg/d) was greater than daily weight gain of treatment 1 calves (0.55 kg/d). At 60 d of age, the mean body weight of treatment two calves was 53% (39 kg) greater than the mean body weight of treatment 1 calves. Total numbers of blood leukocytes and the composition of the mononuclear leukocyte population were unaffected by the plane of nutrition. Mitogen-induced DNA-synthesis and immunoglobulin M secretion also were unaffected by dietary treatment. Blood mononuclear leukocytes from calves on intensified diets, however, produced less interferon-gamma and more inducible nitric oxide, suggesting that increased dietary energy and protein affects specific aspects of leukocyte function associated with cell-mediated immunity. The impact of altered interferon-gamma and NO production on the calf s susceptibility to infectious disease are not known. Mononuclear leukocyte populations from all calves also demonstrated age-related changes in composition and functional capacity, likely reflecting natural exposure to infectious agents and maturation of the calfs immune system.

Aging↗

PubMed2006

Utility of plasma N-terminal brain natriuretic peptide as a marker of functional capacity in patients with chronic severe mitral regurgitation.

Plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) are elevated in severe mitral regurgitation, but their relation to functional capacity and cardiac remodeling is not well defined. We evaluated the role of NT-pro-BNP as a marker of functional capacity, symptoms, and cardiac remodeling in 38 patients with severe degenerative mitral regurgitation and preserved left ventricular ejection fraction. The NT-pro-BNP levels increased progressively with New York Heart Association (NYHA) functional class: NYHA class I (geometric mean [GM] 97.1 pg/ml), NYHA class II (GM 169.8 pg/ml), and NYHA III (GM 457.6 pg/ml; p = 0.015). The end-systolic volume index (r = 0.52, p = 0.001), end-diastolic volume index (r = 0.46, p = 0.003), left atrial volume index (r = 0.4, p = 0.01), regurgitant volume index (r = 0.38, p = 0.02), regurgitant fraction (r = 0.46, p = 0.003), and end-diastolic sphericity index (r = 0.56, p <0.001) all correlated significantly with NT-pro-BNP. The NT-pro-BNP levels correlated significantly with the exercise parameters: maximum oxygen uptake (r = -0.6, p <0.001), exercise time (r = -0.52, p <0.001), and oxygen pulse (r = -0.57, p <0.001). In contrast, only weak correlations were obtained between the exercise and echocardiographic variables. NT-pro-BNP was a strong independent predictor of maximum oxygen uptake (p = 0.001). In conclusion, the results of this study have demonstrated that NT-pro-BNP increases progressively with worsening symptoms, is linked to the extent of LV remodeling, and is an independent predictor of functional capacity. NT-pro-BNP may have a role in the optimal treatment of patients with severe mitral regurgitation.

Analysis of Variance↗

PubMed1999

Comparison of performance-based and self-rated functional capacity in Spanish elderly.

Recent data have shown differences between Spain and the United States in the prevalence of reported disability among community elderly. Differences in reporting functional capacity by culture may contribute to these observed differences. The purpose of this study was to estimate the agreement between self-report of disability and performance-based measures for some basic mobility tasks in the community-dwelling elderly of a Mediterranean country. Interviews containing questions about difficulty for walking and rising from a chair, and performance-based measures (walking speed and chair stand tests) were carried out in 626 individuals aged 72 years and older in Barcelona, Spain. Kappa statistics were calculated, and logistic regression models were constructed to identify possible factors associated with under- and overreporting functional capacity. Moderate kappas (0.41-0.55) were found between self-report and performance-based measures. Patients who rated their health as "poor or very poor" were less likely to underreport disability (adjusted odds ratio (OR) = 0.2, 0.4) but more likely to overreport it (adjusted OR = 23.4, 9.9). No significant agreement differences by sex or informant source were found. These findings suggest that Spanish elderly self-report functional capacity accurately and that, contrary to previous results among US elderly, the direction of the observed disagreement is not systematic.

Activities of Daily Living↗

PubMed2003

Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension.

BACKGROUND: The prognosis and functional capacity of patients with pulmonary arterial hypertension (PAH) is poor, and there is a need for safe, effective, inexpensive oral treatments. A single dose of sildenafil, an oral phosphodiesterase type-5 (PD-5) inhibitor, is an effective and selective pulmonary vasodilator in PAH. However, the long-term effects of PD-5 inhibition and its mechanism of action in human pulmonary arteries (PAs) are unknown. METHODS AND RESULTS: We hypothesized that 3 months of sildenafil (50 mg orally every 8 hours) added to standard treatment would be safe and improve functional capacity and hemodynamics in PAH patients. We studied 5 consecutive patients (4 with primary pulmonary hypertension, 1 with Eisenmenger's syndrome; New York Heart Association class II to III). Functional class improved by > or =1 class in all patients. Pretreatment versus posttreatment values (mean+/-SEM) were as follows: 6-minute walk, 376+/-30 versus 504+/-27 m, P<0.0001; mean PA pressure, 70+/-3 versus 52+/-3 mm Hg, P<0.007; pulmonary vascular resistance index 1702+/-151 versus 996+/-92 dyne x s x cm(-5) x m(-2), P<0.006. The systemic arterial pressure was unchanged, and no adverse effects occurred. Sildenafil also reduced right ventricular mass measured by MRI. In 7 human PAs (6 cardiac transplant donors and 1 patient with PAH on autopsy), we showed that PD-5 is present in PA smooth muscle cells and that sildenafil causes relaxation by activating large-conductance, calcium-activated potassium channels. CONCLUSIONS: This small pilot study suggests that long-term sildenafil therapy might be a safe and effective treatment for PAH. At a monthly cost of 492 dollars Canadian, sildenafil is more affordable than most approved PAH therapies. A large multicenter trial is indicated to directly compare sildenafil with existing PAH treatments.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1998

Development of a walking test for the assessment of functional capacity in non-anaemic maintenance dialysis patients.

BACKGROUND: Walk tests may be useful adjuncts or even alternatives to the assessment of peak oxygen uptake (VO2 peak) in patients with low functional capacity. Walk tests are easy to administer, appear to be well tolerated by patients and may represent a more meaningful measure for a patient group as they assess capability as well as fitness. However, the use of walk tests for the assessment of functional capacity in maintenance dialysis patients has received scant attention. The aim of this study was to assess the validity of a walking-stair-climbing test to predict VO2 peak in non-anaemic maintenance dialysis patients. METHODS: In the validation phase of the study, 14 subjects completed a cycle ergometer-graded exercise test (GXT) for the determination of VO2 peak and a walking-stair-climbing task (WALK), each separated by a period of 7 days. Three weeks later, 18 subjects completed two WALK tests, each separated by a period of at least 48 h, to facilitate reliability estimation. Estimates of differentiated and undifferentiated ratings of perceived exertion (RPE) were obtained during and immediately consequent to all exercise tests. RESULTS: VO2 peak (ml kg min) was significantly correlated with total WALK time (s) (r = -0.83; P < 0.001). VO2 peak (ml/kg/min) could be predicted from total WALK time with a standard error of prediction of 11%. Reliability assessment revealed no significant differences for any aspect of the WALK test performance, with intraclass correlation coefficients ranging from r = 0.71 (RPElegs) to 0.96 (total WALK time). CONCLUSION: These results indicate that the WALK test is a valid, reliable and potentially useful method by which to assess the functional capacity of non-anaemic maintenance dialysis patients.

Aged↗

PubMed2000

Maximal functional capacity in patients with Chagas' cardiomyopathy without congestive heart failure.

BACKGROUND: Chagas' disease is a known dilated form of cardiomyopathy. However, a great number of patients, although showing electrocardiographic (ECG) well-recognized changes, maintain normal ventricular chamber dimensions and are asymptomatic. The aim of the present study was to objectively characterize functional capacity in asymptomatic patients with Chagas' disease and normal left ventricular function. METHODS AND RESULTS: Eighteen asymptomatic male patients with Chagas' disease, aged 33+/-6 years, were selected for the study. All showed ECG changes typical of the disease, as well as left ventricular fractional shortening (LVFS) greater than 0.30 on M-mode 2-dimensionally guided echocardiography. Twenty sedentary normal male patients, aged 29+/-6 years, served as controls. Both groups were submitted to ergoespirometry testing for assessment of exercise functional capacity. Patients with Chagas' disease, when compared with controls, showed lower (P < .001) maximal O2 consumption (VO2max, 24.3+/-4.2 v 37.0+/-5.4 mL x kg(-1) x min(-1) respectively); O2 pulse rate (PO2max, 10.5+/-1.4 v 15.1+/-2.5 mL/beat, respectively); maximal ventilation (VEmax, 50.1+/-13.5 v 113.0+/-17.6 L x min(-1), respectively); anaerobic threshold of maximal O2 consumption (VO2-AT, 15.8+/-3.6 v 24.6+/-4.7 mL x kg(-1) x min(-1), respectively); and maximal heart rate (HRmax, 154+/-21 v 186+/-7 beat x min(-1), respectively). CONCLUSIONS: Asymptomatic patients with Chagas' disease, although presenting normal left ventricular systolic function at rest, display a substantial impairment of exercise functional capacity.

Adult↗