Thomas Manfredi

Plasma creatine kinase activity and exercise-induced muscle damage in older men

Plasma creatine kinase (CK) activity has often been used as a marker of exercise-induced skeletal muscle damage. While the pattern of muscle damage following eccentric exercise has been established in young adults, there is little data available on eccentric exercise-induced muscle damage in older individuals. The purpose of this study was to compare ultrastructural changes in skeletal muscle following high intensity eccentric exercise of young and older men and to determine whether CK activity is a reliable predictor of muscle damage. Five young (20-30 yr) and five older untrained men (59-63 yr) performed three 15-min bouts of eccentric exercise at 90, 80, and 70% of maximal concentric power output. There was a prolonged increase in CK up to 10 d following exercise that was not significantly different between groups. Light and electron microscopic examination of needle biopsies obtained from the vastus lateralis showed evidence of focal damage in greater than 90% of the post-exercise fibers examined in the older subjects, compared with values ranging from 5 to 50% reported previously in young subjects. Quantitative analysis using light microscopy showed greater damage in the older subjects than reported previously in young subjects. These data suggest that older adults experience greater muscle damage following eccentric exercise than young subjects, which may be due in part to the smaller muscle mass and lower VO2max seen in older men. In addition, there was no relationship between CK activity and the corresponding amount of muscle damage observed in each subject, suggesting that CK activity may be a poor predictor of exercise-induced muscle damage.

GOING SEPARATE WAYS? SCHOOL-TO-WORK TRANSITIONS IN THE UNITED STATES AND EUROPE

This paper derives school-to-work transition pathways in the United States and Europe between the late 1990s and the early 2000s. To do so, it uses Optimal Matching, a technique developed to sequence DNA. The key advantage of using this technique is that, rather than focusing on a specific point in time or a single destination, such as employment, inactivity or unemployment, they convey information on all activities undertaken by youth over the transition period, their sequence and their persistence. Strong similarities are found between the United States and Europe. However, pathways in the United States are characterised by significantly more dynamism than in Europe: youth in employment tend to change jobs more frequently while inactive or unemployed youth are more likely to experience several short spells rather than a single long one. School-to-work transition pathways in the United States also involve less time spent in unemployment than in Europe. The share of school-leavers involved in pathways dominated by employment is larger in the United States than in Europe and non-employment traps are less frequent in the United States. The most successful European countries in terms of school-to-work transitions are those where apprenticeships are widespread. On the other hand, European countries with a high incidence of temporary work among youth have a significantly smaller share of youth belonging to pathways dominated by employment and a larger share of youth in pathways characterised by frequent job changes separated by long unemployment spells. At the individual level, qualifications, gender, ethnicity and motherhood are found to influence the probability of disconnecting from the labour market and education for a prolonged period of time. Overall, the analysis shows the potential of Optimal Matching as a descriptive tool for the study of school-to-work transitions. It also tentatively explores how pathways obtained through Optimal Matching could be used for further analysis to draw policy-relevant conclusions. At present, data availability appears to be the main barrier to fully exploiting this novel technique. Cet article analyse les trajectoires de transition de l’ecole a l’emploi aux Etats-Unis et en Europe entre la fin des annees 1990 et le debut des annees 2000. Pour ce faire, il utilise « l’Optimal Matching », une technique developpee pour l’analyse des sequences d’ADN. Le principal atout de cette technique est qu’au lieu de se concentrer sur un moment specifique ou sur une seule activite, telle que l’emploi, l’inactivite ou le chomage, elles vehiculent de l’information sur toute les activites entreprises par les jeunes pendant la periode de transition, leur chronologie et leur perseverance. On constante de nombreuses similarites entre les Etats-Unis et l’Europe. Toutefois, les trajectoires aux Etats-Unis sont caracterisees par beaucoup plus de dynamisme qu’en Europe : les jeunes occupes ont tendance a changer d’emploi plus frequemment et les episodes de chomage sont plus souvent cours et repetes que de longue duree. Les trajectoires de transition de l’ecole a l’emploi aux Etats-Unis sont aussi caracterisees par moins de temps passe au chomage qu’en Europe. La proportion de jeunes quittant l’ecole qui entame des trajectoires dominees par l’emploi est plus importante aux Etats-Unis qu’en Europe et les pieges du non-emploi sont moins frequents aux Etats-Unis. Les pays europeens les plus performants en termes de transitions de l’ecole a l’emploi sont ceux ou l’apprentissage est le plus repandu. D’autre part, les pays europeens a forte incidence de l’emploi temporaire parmi les jeunes, presentent une part plus faible de jeunes dans les trajectoires dominees par l’emploi et une part plus importante de jeunes dans les trajectoires marquees par plusieurs changements d’emploi separes par de longs episodes de chomage. Au niveau individuel, le niveau de qualification, le sexe, l’origine ethnique et la maternite influencent la probabilite de se deconnecter du marche du travail et du systeme educatif pour une periode prolongee. Globalement, l’analyse montre le potentiel de l’Optimal Matching comme outil descriptif dans l’etude des transitions de l’ecole a l’emploi. Cet article tente egalement d’utiliser les trajectoires obtenues avec l’application de l’Optimal Matching pour en tirer des conclusions politiques. La disponibilite de donnees est actuellement la principale barriere a l’exploitation a part entiere de cette nouvelle technique.

Exercise training effects on skeletal muscle plasticity and IGF-1 receptors in frail elders

Age-related sarcopenia inhibits mobility, increasing the risk for developing many diseases, including diabetes, arthritis, osteoporosis, and heart disease. Tissue plasticity, or the ability to regenerate following stress, has been a subject of question in aging humans. We assessed the impact of 10-weeks of resistance training on markers of skeletal muscle plasticity and insulin growth factor-1 (IGF-1) receptor density in a sub sample of subjects who, in an earlier study, demonstrated enhanced immunohistochemical labeling of IGF following resistance training. Muscle biopsies from the vastus lateralis of five elderly men and women were taken prior to and following 10 weeks of resistance training (N = 3) or a control period (N = 2). Immunogold labeling and quantitative electron microscopy techniques were used to analyze markers of IGF-1 receptor density and tissue plasticity. The experimental subjects showed a 161 ± 93.7% increase in Z band damage following resistance training. Myofibrillar central nuclei increased 296 ± 120% (P = 0. 029) in the experimental subjects. Changes in the percent of damaged Z bands were associated with alterations in the presence of central nuclei (r = 0.668; P = 0.0347). Post hoc analysis revealed that the relative pre/post percent changes in myofibrillar Z band damage and central nuclei were not statistically different between the control and exercise groups. Exercise training increased myofibrillar IGF-1 receptor densities in the exercise subjects (P = 0.008), with a non-significant increase in the control group. Labeling patterns suggested enhanced receptor density around the Z bands, sarcolemma, and mitochondrial and nuclear membranes. Findings from this study suggest that the age-related downregulation of the skeletal muscle IGF-1 system may be reversed to some extent with progressive resistance training. Furthermore, skeletal muscle tissue plasticity in the frail elderly is maintained at least to some extent as exemplified by the enhancement of IGF-1 receptor density and markers of tissue regeneration

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 m2, 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.

Physiological and Anthropometrical Predictors of 15-Kilometer Time Trial Cycling Performance Time

Abstract The purpose of this study was to assess the relationship between physiological and anthropometrical variables and 15-km time trial (TT) cycling performance time. Twenty-two competitive cyclists averaged 59.7 ml · kg–1 · min–1 for maximal oxygen consumption ([Vdot]O2max), 42.8 ml · kg–1 · min–1 for anaerobic threshold (AT), and 23.5 min for the 15 km TT race. The relationship between [Vdot]O2max and cycling performance time was r = – 0.68, (p < .01) while the correlation between AT and performance time was r = – 0.93, (p <.01). Applying stepwise multiple regression analysis, the two-variable model of the AT and the body circumference ratio, thigh+calf:arm+chest, was found to correlate highly with cycling performance time (r =0.966). It was concluded that the successful cyclists are characterized by the ability to consume large amounts of oxygen prior to ventilatory changes associated with the anaerobic threshold as well as a larger lower to upper body circumference ratio which may favorably decrea...

Estimating oxygen consumption during treadmill and arm ergometry activity in males with coronary artery disease.

PURPOSE This study compared the accuracy of common clinical treadmill and arm ergometry equations in estimating the rate of oxygen consumption for males with coronary artery disease. METHODS Measured and estimated submaximal and maximal oxygen consumption (VO2sub and VO2max) were compared during clinical treadmill (TM) and arm ergometry (AE) graded exercise tests in 15 males with established coronary artery disease (CAD). Estimated VO2sub and VO2max were derived from popular modality specific estimation equations, including those of the American College of Sports Medicine, Bruce and colleagues, Balady and colleagues, and Manfre and colleagues. RESULTS The American College of Sports Medicine (ACSM) 1991 TM equation overestimated VO2sub from 0.3 +/- 0.6 to 1 +/- 0.7 metabolic equivalents (METS) and VO2max by 3 +/- 3 METS, whereas the Bruce Normal Submax and Bruce Cardiac Submax equations inaccurately estimated VO2sub from -1 +/- 0.6 to 0.9 +/- 0.7 METS. The Bruce Active Max and Bruce Sedentary Max equations overestimated VO2max from 1 +/- 2 to 2 +/- 2 METS, whereas the Bruce Cardiac Max equation accurately estimated oxygen consumption at maximal exercise. The ACSM and Manfre Healthy AE equations underestimated VO2sub at low and intermediate workloads from 0.4 +/- 0.4 to 0.8 +/- 0.4 METS. However, the Balady Male and Manfre Cardiac AE equations underestimated VO2 at each submaximal work load from 0.6 +/- 0.3 to 1 +/- 0.6 METS and at maximal work loads from 0.8 +/- 0.9 to 2 +/- 0.8 METS. The ACSM and Manfre Healthy AE equations accurately estimated VO2 at greater submaximal work loads and at maximal exercise. CONCLUSIONS These data suggest that the ability to estimate VO2 in males with CAD is more accurately performed during nonweight-bearing arm activity, although the reason is not entirely understood, and significant inconsistencies exist in the ability to accurately estimate VO2 during treadmill exercise. These data further suggest concern regarding exercise prescription from estimated values derived from both treadmill and arm ergometry tests, because submaximal, and in some instances maximal, estimations were inaccurate. Future research should focus on the development of accurate estimations for those with CAD, primarily during submaximal work.

Exercise and dietary cholesterol alter rat myocardial capillary ultrastructure

Abstract  The effects of a cholesterol-rich diet and exercise training on the myocardial capillary network and capillary ultrastructure were examined using Sprague-Dawley rats subjected to a 7-week exhaustive swimming scheme. A total of 16 animals were randomly divided into four groups consisting of normal dietinactive, normal dietexercise, cholesterol dietinactive, and cholesterol dietexercise. Following the experimental regimen the largest heart-mass-to-body-mass ratios were measured for the exercised rats fed a normal diet and the smallest ratios were found for the cholesterol-fed inactive rats. The capillary-to-fiber ratios and the capillary densities of the exercise-trained animals fed normal and cholesterol-containing diets were higher than those of either of the inactive groups. Diet and exercise had significant and opposing effects on the number of capillary pinocytotic vesicles and no significant effect on vesicle size. The capillary endothelium of the exercise-trained animal groups occupied a smaller proportion of the capillary area when compared to diet-matched inactive groups. The results of this study imply that exercise training and a cholesterol-containing diet have opposite effects on the heart-mass-to-body-mass ratio and capillary pinocytotic vesicle number. Furthermore, exercise increases the capillary network of the myocardium and may facilitate receptor-mediated transport in heart capillaries.

Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy

Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor γ agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.

Postmenopausal effects of resistance training on muscle damage and mitochondria.

Abstract Manfredi, TG, Monteiro, MA, Lamont, LS, Singh, MF, Foldvari, M, White, S, Cosmas, AC, and Urso, ML. Postmenopausal effects of resistance training on muscle damage and mitochondria. J Strength Cond Res 27(2): 556–561, 2013—The purpose of this study was to measure the effects of a 12-month progressive resistance training intervention on muscle morphology and strength gains in postmenopausal women. Skeletal muscle biopsies were obtained from the vastus lateralis of 5 independent community-dwelling women (mean age: 75.6 ± 4.28 years; mean height: 163 ± 5.34 cm; mean weight: 72 ± 17.5 kg) before 6 months and 12 months after progressive resistance training. Muscle strength (1 repetition maximum) was measured at the same time points. After 6 months of training, morphological analysis revealed evidence of increased proteolysis and tissue repair, and rudimentary fiber development. The percent of Z-bands with mild Z-band disruption increased from 43.9% at baseline to 66.7% after 6 months of training (p < 0.01). Mitochondrial volume also increased (percent of mitochondria = 0.86% at baseline, 1.19% at 6 months, and 1.04% at 12 months, p < 0.05), and there was a shift to larger sized mitochondria. The training did not result in statistically significant increases in muscle leg strength (p < 0.18). It appears that mild Z-band disruption acts as a precursor for increased protein synthesis and stimulates an increase in mitochondrial mass. Therefore, although a progressive resistance training program in this population did not increase muscle strength, it did demonstrate clinical applications that lend support to the importance of resistance training in older adults.

Mechanical function, glycolysis, and ultrastructure of perfused working mouse hearts following thoracic aortic constriction.

BACKGROUND Glycolytic flux in the mouse heart during the progression of left ventricular hypertrophy (LVH) and mechanical dysfunction has not been described. METHODS The main objectives of this study were to characterize the effects of thoracic aortic banding, of 3- and 6-week duration, on: (1) left ventricular (LV) systolic and diastolic function of perfused working hearts quantified by analysis of pressure-volume loops; (2) glycolytic flux in working hearts expressed as the rate of conversion of (3)H-glucose to (3)H(2)O, and (3) ultrastructure of LV biopsies assessed by quantitative and qualitative analysis of light and electron micrographs. RESULTS Results revealed that (1) indexes of systolic function, including LV end-systolic pressure, cardiac output, and rate of LV pressure development and decline, were depressed to similar degrees at 3 and 6 weeks post-banding; (2) diastolic dysfunction, represented by elevated LV end-diastolic pressure and volume, was more severe at 6 than at 3 weeks, consistent with a transition to failure; (3) a progressive decline in glycolytic flux that was roughly half the control rate by 6 weeks post-banding; and (4) structural derangements, manifested by increases in interstitial collagen content and myocyte Z-band disruption, that were more marked at 3 weeks than at 6 weeks. CONCLUSION The results are consistent with the view that myocyte damage, fibrosis, and suppressed glycolytic flux represent maladaptive structural and metabolic remodeling that contribute to the development of failure in high pressure load-induced LVH in the mouse.