Search PubMed⌕ Search

Biomedical subjects

Ronenn Roubenoff

Publications and source records attributed to Ronenn Roubenoff.

At least 19 recordsLinked to original sources

Effect of vitamin E and eccentric exercise on selected biomarkers of oxidative stress in young and elderly men.

Muscle damage resulting from eccentric exercise provides a useful model of oxyradical-induced injury and can be used to examine age-related responses to oxidative stress. Sixteen young (26.4 +/- 3.3 years) and 16 older (71.1 +/- 4.0 years) healthy men were randomly assigned to 1000 IU/d vitamin E or placebo for 12 weeks and ran downhill for 45 min at 75% VO(2)max, once before and following supplementation. Blood samples were obtained before (baseline) and immediately postexercise (0 h), and at 6, 24, and 72 h postexercise to determine antioxidant status, muscle damage, lipid peroxidation, and DNA damage. Following exercise, young and older men experienced similar increases in serum creatine kinase (CK), F(2alpha)-isoprostanes (iPF(2alpha); p <.001) and malondialdehyde (MDA; p <.01), although iPF(2alpha) peaked at 72 h postexercise and MDA peaked at 0 h. Oxygen Radical Absorbance Capacity (ORAC) decreased at 72 h (p <.01) and correlated with the rise in iPF(2alpha), MDA, and CK in the young men (p <.05). Leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) was unaffected by exercise. Vitamin E decreased peak CK in young men, while in older men it decreased resting levels of iPF(2alpha) and suppressed the 24 h postexercise increases in iPF(2alpha) (p <.05). Thus, vitamin E supplementation induced modest changes eccentric exercise-induced oxidative stress, although differentially between the young and older subjects, while age had no direct influence on these responses among this group of physically fit subjects.

8-Hydroxy-2'-Deoxyguanosine↗

Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction: the Framingham Heart Study.

BACKGROUND: Experimental studies support a key role for cytokines in left ventricular remodeling. In congestive heart failure (CHF) patients, elevated plasma cytokine levels are associated with worse functional status and adverse prognosis. It is unclear whether cytokine levels can predict the incidence of CHF in asymptomatic individuals. METHODS AND RESULTS: We investigated the relations of serum interleukin-6 (IL-6), C-reactive protein (CRP), and spontaneous production of tumor necrosis factor-alpha (TNFalpha) by peripheral blood mononuclear cell (PBMC) to CHF incidence among 732 elderly Framingham Study subjects (mean age 78 years, 67% women) free of prior myocardial infarction and CHF. On follow-up (mean 5.2 years), 56 subjects (35 women) developed CHF. After adjustment for established risk factors, including the occurrence of myocardial infarction on follow-up, there was a 60 (PBMC TNFalpha) to 68% (serum IL-6) increase in risk of CHF per tertile increment in cytokine concentration (P=0.04, and 0.03, respectively, for trend). A serum CRP level > or =5 mg/dL was associated with a 2.8-fold increased risk of CHF (P=0.02). Subjects with elevated levels of all 3 biomarkers (serum IL-6 and PBMC TNFalpha >median values, CRP> or =5 mg/dL) had a markedly increased risk of CHF (hazards ratio 4.07 [95% CI 1.34 to 12.37], P=0.01) compared with the other subjects. CONCLUSIONS: In our elderly, community-based sample, a single determination of serum inflammatory markers, particularly elevated IL-6, was associated with increased risk of CHF in people without prior myocardial infarction. Additional epidemiological investigations are warranted to confirm the contribution of inflammation to the pathogenesis of CHF in the general population.

Aged↗

Abnormal vitamin B(6) status is associated with severity of symptoms in patients with rheumatoid arthritis.

PURPOSE: Patients with rheumatoid arthritis have low plasma vitamin B(6) levels and elevated plasma homocysteine responses to a methionine load. We examined whether these abnormalities are associated with clinical and biochemical indicators of disease status. METHODS: We performed a cross-sectional study in 37 patients who met the American College of Rheumatology criteria for rheumatoid arthritis. Vitamin B(6) status was assessed by the plasma pyridoxal 5'-phosphate level and with the homocysteine response to a methionine load test. Clinical disease activity was assessed by joint counts, the Health Assessment Questionnaire disability score, and biochemical markers of the acute phase response. RESULTS: Plasma pyridoxal 5'-phosphate levels were inversely correlated with the erythrocyte sedimentation rate (r = -0.37, P = 0.02), C-reactive protein level (r = -0.52, P = 0.002), disability score (r = -0.37, P = 0.02), morning stiffness (r = -0.38, P = 0.02), and degree of pain (r = -0.33, P = 0.04). The increase in homocysteine levels after a methionine load correlated with the erythrocyte sedimentation rate (r = 0.39, P = 0.02), C-reactive protein level (r = 0.37, P = 0.03), disability score (r = 0.37, P = 0.04), degree of pain (r = 0.38, P = 0.02) and fatigue (r = 0.42, P = 0.01), number of painful joints (r = 0.43, P = 0.007), and number of swollen joints (r = 0.32, P = 0.05). CONCLUSION: Markers of vitamin B(6) status are associated with disease activity and severity, synovial burden, and pain in patients with rheumatoid arthritis, raising the possibility that impaired vitamin B(6) status in these patients is a result of inflammation.

Adult↗

Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men.

AIMS: The influence of ageing on the pharmacokinetics of zolpidem, an extensively prescribed hypnotic medication, was evaluated in healthy human volunteers. METHODS: A series of 16 elderly (age: 61-85 years) and 24 young (age: 22-42 years) volunteers received single 5 mg oral doses of zolpidem tartrate. Serum zolpidem concentrations were determined by HPLC with fluorescence detection in samples drawn during 8 h after dosage. The effect of testosterone on zolpidem biotransformation was evaluated in vitro using human liver microsomes. Possible induction of CYP3A protein expression and function was studied in cultured human hepatocytes. RESULTS: Among men, apparent oral clearance of zolpidem was decreased in elderly compared to young subjects (3.8 vs 11.0 ml min-1 kg-1, P < 0.01), Cmax was increased (93 vs 40 ng ml-1, P < 0.01), and half-life increased (2.7 vs 1.5 h, P < 0.03). Among women, zolpidem oral clearance was decreased in the elderly (3.0 vs 5.8 ml min-1 kg-1, P < 0.02), Cmax increased (108 vs 60 ng ml-1, P < 0.001), with no difference in t1/2 (2.3 vs 2.4 h). Among male subjects, free serum testosterone concentrations were lower in the elderly (10.5 vs 19.0 pg ml-1, P < 0.01), and were significantly correlated with zolpidem clearance (r2 = 0.46, P < 0.001). Multiple regression analysis indicated a greater relative contribution of serum testosterone than age to the oral clearance of zolpidem among men. In human liver microsomes, co-incubation of zolpidem (10 micro m) with varying concentrations of testosterone produced activation of biotransformation of zolpidem to its principal hydroxylated metabolite. Maximum activation was achieved at equimolar concentrations of testosterone (10 micro m). However, testosterone did not induce immunoactive CYP3A4 expression or catalytic function in cultured human hepatocytes. CONCLUSIONS: The increased Cmax and lower oral clearance of zolpidem in the elderly are consistent with recommendations of lower clinical doses of zolpidem in the elderly. Our clinical and in vitro data both suggest that reduced free serum testosterone may have a modulatory role in age-dependent changes in zolpidem pharmacokinetics in men.

Administration, Oral↗

Insulin-like growth factor-1 and interleukin 6 predict sarcopenia in very old community-living men and women: the Framingham Heart Study.

OBJECTIVES: To assess the prognostic role of the inflammatory cytokine, interleukin 6 (IL-6), and insulin-like growth factor-1 (IGF-1) in predicting 2-year changes in fat-free mass (FFM) while controlling for potential confounders. DESIGN: Population-based cohort, the Framingham Heart Study, examined in 1992-93 and 1994-95. SETTING: General community. PARTICIPANTS: Two hundred thirty-two men and 326 women aged 72 to 92. MEASUREMENTS: IGF-1 was measured using radio-immunoassay and cellular IL-6 production using non-cross-reacting radioimmunoassays. FFM was estimated using population-specific equations for predicting FFM from bioelectrical impedance analysis developed separately for men and women. RESULTS: Higher IGF-1 predicted smaller loss of FFM in men than lower IGF-1 did (P=.002), after adjusting for age, baseline FFM, fat mass, and 2-year weight changes, whereas cellular IL-6 was a significant predictor of sarcopenia in women (P=.02). Weight change was a strong determinant of change in FFM in both sexes (P<.0001). CONCLUSION: Predictors of sarcopenia include body composition characteristics that are common to men and women and sex-specific metabolic predictors. Sarcopenia appears to reflect a withdrawal of anabolic stimuli, such as growth hormone, in men but an increase in catabolic stimuli, such as cellular IL-6, in women.

Adipose Tissue↗

Plasma pyridoxal 5'-phosphate concentration is correlated with functional vitamin B-6 indices in patients with rheumatoid arthritis and marginal vitamin B-6 status.

Many patients with rheumatoid arthritis (RA) have low plasma pyridoxal-phosphate (PLP) but a normal erythrocyte aspartate aminotransferase activity coefficient (alpha EAST), a measure of vitamin B-6 status in the erythrocytes, compared with healthy subjects. The goal of the present study was to examine the correlations of PLP levels in these two compartments (plasma and erythrocytes) with other established indices of vitamin B-6 status, and to determine which indicator better reflects functional status of vitamin B-6 in patients with RA. Multiple indices of vitamin B-6 status were measured in 33 patients with RA. Plasma PLP, urinary 4-pyridoxic acid (4-PA), net increase in plasma total homocysteine after a methionine load (DeltatHcy) and net increase in urinary xanthurenic acid after a tryptophan load (DeltaXA) were log-transformed to reach normality for statistical analyses. We found that log-plasma PLP levels were inversely correlated with both log-DeltatHcy (r = -0.368, P = 0.035) and log-DeltaXA (r = -0.333, P = 0.05). Plasma PLP was not correlated with alpha EAST or urinary 4-PA excretion. In contrast, erythrocyte PLP was inversely correlated with alpha EAST (r = -0.431, P = 0.012) and positively correlated with log-4-PA (r = 0.475, P = 0.005), but erythrocyte PLP was not correlated with the outcomes of a methionine or tryptophan load test. Erythrocyte PLP and log-4-PA, but not plasma PLP, were correlated with dietary intake of vitamin B-6 after adjusting for protein intake (r = 0.420, P = 0.015 and r = 0.333, P = 0.05, respectively). We suggest that in patients with RA, plasma PLP levels are a better diagnostic indicator of functional vitamin B-6 status than erythrocyte PLP levels.

Adult↗

Catabolism of aging: is it an inflammatory process?

PURPOSE OF REVIEW: Research in the field of sarcopenia is evolving rapidly, and the process is now recognized as an important cause of frailty and morbidity in the elderly. This review focuses on recent developments in the field, especially regarding the role of catabolic stimuli in causing sarcopenia. RECENT FINDINGS: There is now an impressive body of literature implicating increased interleukin-6 levels in successfully aging adults. New data indicate that high interleukin-6 levels carry a poor prognosis, although it is not clear if the cytokine has primarily a causal or counter-regulatory function. Interleukin-6 and other cytokines could function through direct catabolic effects, or by causing reduced dietary energy intake (the anorexia of aging), or by inducing insulin resistance or lowering growth hormone-insulin-like growth factor-I concentrations. Furthermore, apoptosis has now been linked to sarcopenia, suggesting that an inflammatory signal could trigger loss of muscle cells in the elderly even in the absence of overt inflammatory disease. SUMMARY: Aging causes loss of many of the anabolic signals to muscle that are present in young adulthood. Recent research suggests that there is also an increase in catabolic signals with age.

Aging↗

Cytokine responses differ by compartment and wasting status in patients with HIV infection and healthy controls.

Inflammatory cytokines are implicated in the loss of lean tissue that occurs in patients with inflammatory and infectious diseases, including HIV infection. However, it is not known whether plasma levels or cellular production of cytokines, or their antagonists, are more closely related to lean tissue loss. We studied whether plasma cytokine analysis could substitute for PBMC production assays in studies of nutrition status and disease state, and if cytokine antagonists could offer an alternative in assessing cytokine status. We used a bout of moderately difficult exercise to perturb cytokine production in 12 adults with HIV without wasting, 10 adults with HIV wasting, and nine healthy controls. Plasma and peripheral blood mononuclear cell (PBMC) production of interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra) and soluble TNF receptor type II (sTNFrII) were measured at baseline and 2, 6, 24 and 168h following exercise. PBMC production of IL-1beta, TNF-alpha and IL-6 were all higher in the HIV-infected patients without wasting than in the controls (P<0.05) or the patients with AIDS wasting (P<0.05). Plasma concentrations of TNF-alpha and IL-6 were higher in the HIV wasted patients than in the controls (P<0.05). Both plasma and PBMC levels of sTNFrII were higher in HIV patients, regardless of wasting, than in controls. These data suggest that the PBMC cytokine compartment is more sensitive to nutritional and metabolic abnormalities than is the plasma compartment. PBMC production of IL-1beta, IL-6 and TNF-alpha best distinguish between HIV patients with and without wasting, while plasma concentrations of IL-6 and TNF-alpha are elevated in AIDS wasting, but do not reliably distinguish patients with wasting from HIV-infected patients without wasting.

Adult↗

Cachexia in rheumatoid arthritis is not explained by decreased growth hormone secretion.

OBJECTIVE: Patients with rheumatoid arthritis (RA) lose body cell mass (BCM) by unknown mechanisms. Since the loss of BCM in normal aging individuals parallels the characteristic age-related decline in growth hormone (GH) secretion, this study was carried out to determine whether further decreased GH secretion plays a role in the pathogenesis of this loss of BCM in RA patients, termed "rheumatoid cachexia." METHODS: GH secretory kinetics were determined by deconvolution analysis in 16 patients with RA and 17 healthy controls matched for age (mean +/- SD 45.4 +/- 13.2 years and 47.1 +/- 14.6 years, respectively), sex, race, and body mass index. Blood samples were obtained every 20 minutes for 24 hours. Body composition was ascertained using total-body potassium (TBK) as a measure of BCM and dual x-ray absorptiometry to determine fat mass. RESULTS: BCM was reduced in patients with RA compared with healthy controls (mean +/- SD gm TBK 79.5 +/- 9.5 versus 94.9 +/- 11.9; P < 0.0005), but there was no difference in fat mass. GH kinetic parameters in patients with RA did not differ from those in controls. CONCLUSION: These findings suggest that GH kinetics are unaltered in RA patients compared with healthy subjects; thus, GH deficiency does not account for rheumatoid cachexia.

Adult↗

Metabolic aging and predicted longevity: results of a cross-sectional study in post-menopausal women.

BACKGROUND AND AIMS: The extent to which general characteristics of metabolic aging contribute to differences in life span among individuals remains uncertain. The objective of this study was to examine the association of age-related physiological and metabolic variables with predicted longevity in postmenopausal women. METHODS: Subjects were 33 healthy women aged 55-65 years. Total and resting energy expenditure, body temperature, immune function as assessed by a delayed-type hypersensitivity skin test (DTH), lipid profile, and reported dietary intake were measured. RESULTS: There were no significant associations between longevity, energy expenditure, body temperature, lipid profile, or dietary intake. However, there was a significant association of predicted longevity with DTH (partial r=0.44, p=0.023). CONCLUSIONS: These results suggest that immune function may predict familial differences in longevity, while energy expenditure, body temperature, lipid profile, and dietary intake are unrelated. Although the small sample size may have limited the ability to detect metabolic effects on longevity in this study, the general approach may be broadly applicable to examinations of metabolic aging in humans.

Aged↗

Cachexia in rheumatoid arthritis.

Rheumatoid arthritis is a debilitating, chronic, systemic, autoimmune disease of unknown etiology that causes destruction of joint cartilage and bone. It generally occurs between the fourth and sixth decades of life, and affects two to three times more women than men. It is characterized by joint stiffness, pain, and swelling, and is accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in skeletal muscle, but also occurs in the viscera and immune system. Thus, rheumatoid cachexia leads to muscle weakness and a loss of functional capacity, and is believed to accelerate morbidity and mortality in rheumatoid arthritis. Currently there is no established mechanism for rheumatoid cachexia, but it is accompanied by elevated resting energy expenditure, accelerated whole-body protein catabolism, and excess production of the inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1beta. Tumor necrosis factor-alpha is probably the central mediator of muscle wasting in rheumatoid arthritis, and is known to act synergistically with interleukin-1beta to promote cachexia. In general, tumor necrosis factor-alpha and interleukin-1beta are thought to alter the balance between protein degradation and protein synthesis in rheumatoid arthritis to cause muscle wasting. The precise mechanism by which they do this is not known. Reduced peripheral insulin action and low habitual physical activity are important consequences of rheumatoid arthritis, and have also been implicated as mediators of rheumatoid cachexia. Insulin inhibits muscle protein degradation. Consequently, reduced peripheral insulin action in rheumatoid arthritis is thought to be permissive to cytokine-driven muscle loss. The cause of reduced peripheral insulin action in rheumatoid arthritis is not known, but tumor necrosis factor-alpha has been shown to interfere with insulin receptor signaling and is probably an important contributor. Low habitual physical activity has consistently been observed in rheumatoid arthritis and is an important consequence of, and contributor to, muscle wasting. In addition, low physical activity predisposes to fat gain and is believed to precipitate a negative reinforcing cycle of muscle loss, reduced physical function, and fat gain in rheumatoid arthritis, which leads to 'cachectic obesity'. To date, there is no standard treatment for rheumatoid cachexia. However, physical exercise is currently believed to be the most important and clinically relevant countermeasure against rheumatoid cachexia. In general, a combination of skeletal muscle strength training and aerobic exercise is recommended, but must be prescribed with the patient's disease status, overall health, and safety in mind. Future studies should investigate the safety, efficacy, and required dose of anti-cytokine therapy for the treatment of rheumatoid cachexia. In this review, we outline the current definition of rheumatoid cachexia, and discuss the etiology, pathogenesis, and treatment of rheumatoid cachexia.

Arthritis, Rheumatoid↗

Eating behavior correlates of adult weight gain and obesity in healthy women aged 55-65 y.

BACKGROUND: The specific underlying causes of adult weight gain remain uncertain. OBJECTIVE: The objective was to determine the association of 3 measures of eating behavior with weight gain and body mass index (BMI; in kg/m(2)) in adults. DESIGN: Current dietary restraint, disinhibition, and hunger were assessed with the use of the Eating Inventory in 638 healthy, nonsmoking women aged 55-65 y. In addition, subjects reported their current weight and height, their weight for 6 age intervals, and changes in voluntary dietary energy restriction over the past 10 y. Current weight and height were validated in 10% of subjects. RESULTS: Current disinhibition strongly predicted weight gain and current BMI (partial r = 0.27 and 0.34, respectively, both P < 0.001). Neither restraint nor hunger was a significant independent predictor of either variable, but the positive associations between disinhibition and both weight gain and BMI were attenuated by restraint (P = 0.016 and 0.010, respectively, after adjustment for confounding variables). In the subpopulation of women who reported a stable level of voluntary dietary energy restriction, disinhibition also strongly predicted weight gain and higher BMI, and restraint was negatively associated with weight gain (partial r = -0.17, P = 0.019). CONCLUSIONS: Higher disinhibition is strongly associated with greater adult weight gain and higher current BMI, and dietary restraint may attenuate this association when disinhibition is high. These findings suggest that eating behavior has an important role in the prevention of adult-onset obesity and that further studies are warranted.

Adult↗

Longitudinal changes in body composition in older men and women: role of body weight change and physical activity.

BACKGROUND: Estimates of body-composition change in older adults are mostly derived from cross-sectional data. OBJECTIVE: We examined the natural longitudinal patterns of change in fat-free mass (FFM) and fat mass (FM) in older adults and explored the effect of physical activity, weight change, and age on these changes. DESIGN: The body composition measured by hydrodensitometry and the level of sports and recreational activity (SRA) of 53 men and 78 women with a mean (+/-SD) initial age of 60.7 +/- 7.8 y were examined on 2 occasions separated by a mean (+/-SD) time of 9.4 +/- 1.4 y. RESULTS: FFM decreased in men (2.0% per decade) but not in women, whereas FM increased similarly in both sexes (7.5% per decade). Levels of SRA decreased more in men than in women over the follow-up period. Baseline age and level of SRA were inversely and independently associated with changes in FM in women only. Neither age nor level of SRA was associated with changes in FFM in men or women. Weight-stable subjects lost FFM. FFM accounted for 19% of body weight in those who gained weight, even in the presence of decreased levels of SRA. Loss of FFM (33% of body weight) was pronounced in those who lost weight, despite median SRA levels >4184 kJ/wk. CONCLUSIONS: On average, FM increased; however, the increase in women was attenuated with advancing age. The decrease in FFM over the follow-up period was small and masked the wide interindividual variation that was dependent on the magnitude of weight change. The contribution of weight stability, modest weight gains, or lifestyle changes that include regular resistance exercise in attenuating lean-tissue loss with age should be explored.

Adipose Tissue↗

Low physical activity reduces total energy expenditure in women with rheumatoid arthritis: implications for dietary intake recommendations.

BACKGROUND: Rheumatoid arthritis (RA) causes cachexia, a metabolic response characterized by loss of muscle mass and elevated resting energy expenditure (REE). However, energy expenditure in physical activity in subjects with RA is lower than that in healthy subjects. It is not known which effect predominates in regulating total energy expenditure (TEE), and thus whether the dietary energy requirements of subjects with RA are higher or lower than those of healthy subjects. OBJECTIVE: Our objective was to determine TEE in women with RA by using the reference method of doubly labeled water ((2)H(2)(18)O). DESIGN: In this case-control study, we examined 20 women with RA and 20 healthy women who were matched for age and body mass index. RESULTS: The patients with RA were cachectic (their body cell mass was 14% lower than that of the controls, P < 0.001), but REE was not elevated, reflecting good disease control. Mean (+/- SD) TEE was 1344 kJ/d lower in the patients than in the controls (9133 +/- 1335 compared with 10 477 +/- 1992 kJ/d; P < 0.02). The energy expenditure in physical activity of the patients was 1034 kJ/d lower than that of the controls (P < 0.04), which accounted for 77% of the difference in TEE between the 2 groups. The physical activity level (TEE/REE) of the patients also tended to be lower than that of the controls (1.70 +/- 0.24 compared with 1.89 +/- 0.36; P < 0.07). CONCLUSION: A low physical activity level is the main determinant of lower-than-normal TEE, and thus energy requirements, in women with RA.

Adult↗

The association of eating behavior with risk for morbidity in older women.

BACKGROUND: Although an influence of eating behavior on dietary intake and physiology has been documented in several studies, the extent to which eating behavior influences long-term health is uncertain. METHODS: Current dietary restraint, disinhibition, and hunger were assessed using the Eating Inventory in 1252 nonsmoking women aged 55 to 65 years. In addition, subjects reported the presence or absence of 22 specific morbidities, along with general demographic information. Logistic regression was used to examine associations between eating behavior scores and morbidity, adjusting for age, prior smoking status, hormone replacement therapy, education level, and body mass index (BMI). RESULTS: In adjusted models excluding BMI, higher disinhibition scores were associated with small increased risks for hypercholesterolemia (odds ratio [OR] 1.04, p =.045), leg cramps (OR 1.05, p =.044), indigestion (OR 1.06, p =.020), and cataract (OR 1.09, p =.036), and a decreased risk of eczema (OR 0.91, p =.008). In addition, higher hunger scores were associated with increased risk of eczema (OR 1.09, p =.026). However, after adjusting for confounding variables plus BMI, higher disinhibition scores were associated with increased risks for low back pain (OR 1.06, p =.031) and constipation (OR 1.10, p =.004), and associations of disinhibition and hunger with eczema were unchanged (OR 0.90, p =.008 and OR 1.09, p =.024, respectively). Dietary restraint was not associated with morbidity in any model. CONCLUSIONS: Higher disinhibition and hunger scores were associated with small alterations in reported morbidity risk in a large population of nonsmoking older women. Although our cross-sectional study design makes the directionality of these relationships unclear, our results suggest at most a relatively minor independent influence of eating behavior constructs on long-term health.

Aged↗

Exercise training alters skeletal muscle mitochondrial morphometry in heart failure patients.

BACKGROUND: Previous research has demonstrated that exercise intolerance in heart failure patients is associated with significant alterations in skeletal muscle ultrastructure and oxidative metabolism that may be more consequential than cardiac output. DESIGN: To examine the effect of exercise training on skeletal muscle mitochondrial size in chronic heart failure patients. METHODS: Six heart failure patients participated in 16-weeks of supervised upper and lower extremity exercise training. At the conclusion of training, percutaneous needle biopsies of the vastus lateralis were taken and electron microscopy was used to assess mitochondrial sizes. RESULTS: The exercise programme resulted in a significant increase in peak maximal oxygen consumption ( P< 0.05) and anaerobic threshold (P < 0.04). Knee extension muscle force increased following training ( P< 0.02). After exercise training, the average size of the mitochondria increased by 23.4% (0.036 to 0.046 mu(2), P< 0.015) and the average shape was unaltered. CONCLUSION: Exercise training with heart failure patients alters skeletal muscle morphology by increasing mitochondrial size, with no change in shape. This may enhance oxidative metabolism resulting in an increased exercise tolerance.

Aged↗