Arthur C. Cosmas

Effects of prior exercise on eccentric exercise-induced neutrophilia and enzyme release.

PURPOSE The purpose of this study was to determine the effects of prior exercise on changes in circulating neutrophils, neutrophil activation, and myocellular enzymes following a standardized bout of eccentric exercise. METHODS Twenty-four male volunteers were randomized into three groups (N = 8). Group C performed 10 sets of 10 eccentric contractions of the quadriceps muscles with both legs (100% of the concentric IRM). Group D and Group F exercised for 2 h at 56%VO2max on a cycle ergometer followed by a similar bout of eccentric contractions. Group F also received 7.5 mL x kg(-1) of a carbohydrate-electrolyte beverage every 30 min during the submaximal exercise, whereas group D received no fluid. RESULTS Body weight remained unchanged in groups C and F and decreased in group D by 1.56 +/- 0.34 kg. Ultrastructural Z-Band damage increased three-fold following exercise and remained elevated 3 d after exercise but was not different among groups. Circulating neutrophils were elevated more in group D compared with those in group C immediately after the exercise or rest period, and this difference persisted 3 h after the eccentric exercise. Serum lactoferrin concentrations increased 3.3-fold after exercise in all groups (P < 0.01). Creatine kinase levels (CK) rose in all subjects, with subjects in Group F and D having a significantly greater rise in CK after exercise compared with those in group C. CONCLUSIONS These data indicate that submaximal exercise followed by a bout of eccentric exercise results in similar amounts of myofibrillar injury with a larger neutrophil response and CK release.

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.

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.

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.

Age and diet alter skeletal muscle tubular aggregates

Tubular aggregates (TA’s) may comprise the major histopathologic finding in hyperkalemic and normokalemic periodic paralysis. They also constitute a conspicuous morphologic abnormality in a number of myopathies, and have been associated with non-specific muscle myalgias/cramps. Caloric restriction (CR) is an experimental manipulation that increases longevity and reduces lesions in mice as compared to animals fed ad libitum (AL). However, the impact of CR on the dynamics of muscle tissue has not been previously established. In this paper we week to characterize the relationship between tubular aggregates and age and determine whether they are modulated by caloric restriction.We examined the effects of 40% caloric restriction (CR) on fiber damage formation in middle-aged (19 months of age) and older (27 months) mice. We also examined the effects of age and diet restriction on tubular aggregate formation in 12, 24, and 30 month old mice. Tissue blocks from the 19 and 27 month animals were also examined using electron microscopy for qualitative differences in tubular aggregates which may suggest a diet and age effect.There appeared to be no fiber or Z-disc damage attributable to age as assessed by quantitative light microscopy (LM). Age and diet had significant effects on the percent of fibers occupied by tubular aggregates. Qualitative LM revealed that many TA’s may not have yet penetrated the sarcolemma in the young animals, and in particular, the young CR mice. The presence of round fibers was evident in the young CR mice whereas fibers were more angular in the AL mice.Fiber splitting was also evident in the CR mice, perhaps associated with new fiber formation. Other observations especially prevalent in mice with higher degrees of tubular aggregates included centrally displaced nuclei, nuclear chains among the sarcolemma borders, interfasicular wedging, longitudinally split fibers and cellular infiltrates. Electron microscopic examination of these areas revealed non distinction of the TA ultrastructure as a result of aging and diet. Large clusters of TA’s were observed to be in close approximation with mitochondria and in some instances, mitochondria with internal vesicles were present. We conclude that diet restriction may reduce the accumulation of age-related tubular aggregates in skeletal muscle without altering their ultrastructure.

Diet restriction and age alters skeletal muscle capillarity in B6C3F1 mice

The effects of 40% diet restriction on skeletal muscle fiber area, capillary density (CD) and capillary to fiber ratio (C/F) were compared in 12, 24 and 30-month-old female B6C3F1 female hybrid mice. We hypothesized that diet restriction (DR) would retard the aging effects observed in skeletal muscle, in particular DR would pose opposite effects on skeletal muscle capillarity and fiber area. Samples were prepared for light microscopic examination by standard methods and for morphometric analysis using NIH-image software. There was a significant effect of age on muscle fiber area (p<0.05). The age-associated decrease in fiber area between 12 and 30 months of age was greater (p<0.05) in the ad libitum (AL) (37.7%) animals as compared to the diet restricted (DR) mice (29.2%). Diet had a significant effect on CD (p<0.05) and C/F (p<0.05). This finding suggests that the lower capillarity in the older DR mice may have been due to their larger muscle fibers. The results of this study support the contention that diet restriction delays the progression of age-associated muscle atrophy.

The isolated perfused working mouse heart system

Study of cardioactive agents in vivo is complicated by neurohormonal influences and variations in loading conditions. The working mouse heart perfusion system allows for the ex vivo direct measurement of cardiac metabolism and function, and responses to drugs and hormones, under defined conditions. Myocardial pressure and volume measurements are obtained using a micro-tip catheter inserted into the left ventricular chamber. Direct and derived functional data include heart rate (HR), cardiac output (CO), end systolic pressure (ESP), end diastolic pressure (EDP), end systolic volume (ESV), end diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF). Metabolic data include rates of glycolysis, glucose oxidation, and fatty acid oxidation. The mouse serves as an ideal model for evaluation of the pharmacology and toxicity of novel cardioactive therapeutics due to its rapid reproduction, low cost, and relevance to human physiology.