Biomedical subjects

G L Warren

Publications and source records attributed to G L Warren.

34 records · Page 2Linked to original sources

PubMed1996

Effects of concentric and eccentric training on muscle strength, cross-sectional area, and neural activation.

We compared the effects of concentric (Con) and eccentric (Ecc) isokinetic training on quadriceps muscle strength, cross-sectional area, and neural activation. Women (age 20.0 +/- 0.5 yr) randomly assigned to Con training (CTG; n = 16), Ecc training (ETG; n = 19), and control (CG; n = 19) groups were tested before and after 10 wk of unilateral Con or Ecc knee-extension training. Average torque measured during Con and Ecc maximal voluntary knee extensions increased 18.4 and 12.8% for CTG, 6.8 and 36.2% for ETG, and 4.7 and -1.7% for CG, respectively. Increases by CTG and ETG were greater than for CG (P < 0.05). For CTG, the increase was greater when measured with Con than with Ecc testing. For ETG, the increase was greater when measured with Ecc than with Con testing. The increase by ETG with Ecc testing was greater than the increase by CTG with Con testing. Corresponding changes in the integrated voltage from an electromyogram measured during strength testing were 21.7 and 20.0% for CTG, 7.1 and 16.7% for ETG, and -8.0 and -9.1% for CG. Quadriceps cross-sectional area measured by magnetic resonance imaging (sum of 7 slices) increased more in ETG (6.6%) than in CTG (5.0%) (P < 0.05). We conclude that Ecc is more effective than Con isokinetic training for developing strength in Ecc isokinetic muscle actions and that Con is more effective than Ecc isokinetic training for developing strength in Con isokinetic muscle actions. Gains in strength consequent to Con and Ecc training are highly dependent on the muscle action used for training and testing. Muscle hypertrophy and neural adaptations contribute to strength increases consequent to both Con and Ecc training.

Adolescent↗

PubMed1996

Decreased contraction economy in mouse EDL muscle injured by eccentric contractions.

The objective of this study was to find out whether basal and/or active energy metabolism are altered in isolated mouse extensor digitorum longus muscle injured by eccentric (Ecc) contractions. Measurements of basal O2 consumption and isometric tetanus O2 recovery cost were made at 25 degrees C on muscles that had done either 10 Ecc, 10 isometric (Iso), or no contractions (No). In parallel experiments, rates of lactate and pyruvate production were measured to estimate the anaerobic contribution. Basal O2 consumption was unaffected by the type of protocol performed (P = 0.07). However, the tetanus O2 cost per force-time integral was elevated by 30-36% for the Ecc protocol muscles over that for the Iso and No protocol muscles. When including the increased lactate production by the Ecc protocol muscles, the total energetic cost per force-time integral was 53% higher than that for the Iso protocol muscles [2.35 +/- 0.17 vs. 1.54 +/- 0.18 mumol O2/(N.m.s)]. The decreased economy was attributed to two factors. First, in skinned fibers isolated from the injured muscles, the ratio of maximal actomyosin adenosinetriphosphatase activity to force production was up by 37.5%, suggesting uncoupling of ATP hydrolysis from force production. Second, increased reliance on anaerobic metabolism along with the fluorescent microscopic study of mitochondrial membrane potential and histochemical study of ATP synthase suggested an uncoupling of oxidative phosphorylation in the injured muscles.

Animals↗

PubMed1995

Redistribution of cell membrane probes following contraction-induced injury of mouse soleus muscle.

Our aim was to study how mouse skeletal muscle membranes are altered by eccentric and isometric contractions. A fluorescent dialkyl carbocyanine dye (DiOC18(3)) was used to label muscle membranes, and the membranes accessible to the dye were observed by confocal laser scanning microscopy. Experiments were done on normal mouse soleus muscles and soleus muscles injured by 20 eccentric or 20 isometric contractions. Longitudinal optical sections of control muscle fibers revealed DiOC18(3) staining of the plasmalemma and regularly spaced transverse bands corresponding in location to the T-tubular system. Transverse optical sections showed an extensive reticular network with the DiOC18(3) staining. Injured muscle fibers showed distinctively different staining patterns in both longitudinal and transverse optical sections. Longitudinal optical sections of the injured fibers revealed staining in a longitudinally-oriented pattern. No correlations were found between the abnormal DiOC18(3) staining and the reductions in maximal isometric tetanic force or release of lactate dehydrogenase (P > or = 0.32). Additionally, no difference in the extent of abnormal staining was found between muscles performing eccentric contractions and those performing the less damaging isometric contractions. However, many fibers in muscles injured by eccentric contractions showed swollen regions with marked loss of membrane integrity and an elevated free cytosolic calcium concentration as observed in Fluo-3 images. In conclusion, a loss of cell membrane integrity results from contractile activity, enabling DiOC18(3) staining of internal membranes. The resulting staining pattern is striking and fibers with damaged cell membranes are easily distinguished from uninjured ones.

Animals↗

PubMed1995

Composition analysis of alpha-helices in thermophilic organisms.

We present a statistical comparison of the amino acid composition in a secondary structure element, the alpha-helix, of proteins stable at high temperatures with those which are less so. This study has shown that the temperature-dependent Zimm-Bragg helix propagation value s is not a good predictor for the helix-forming tendency of an amino acid in thermostable proteins. However, we have shown that delta s, the change in s from 20 to 60 degrees C, accurately predicts the direction of the probability shift for 15 amino acids in thermostable protein alpha-helices, although it does not predict the magnitude of that change. The residues tyrosine, glycine and glutamine show a significant increase in residency in alpha-helices for thermostable proteins over their non-thermostable counterparts. Significant decreases in alpha-helix residency occur for the residues valine, glutamic acid, histidine, cysteine and aspartic acid in proteins from thermophilic organisms. Aromatic interactions, hydrogen bonding and a reduction of charge may explain the increase observed for tyrosine and glutamine and the decrease in glutamic acid and aspartic acid, although packing considerations cannot be ruled out. The only physical explanation for the increase in glycine would seem to be its positive delta s value.

Amino Acids↗

PubMed1995

Muscle function and protein metabolism after initiation of eccentric contraction-induced injury.

This study was designed to determine the relationship between skeletal muscle function and protein metabolism after initiation of eccentric contraction-induced injury. Mouse anterior crural muscles were injured in vivo, and then either immediately or 3, 6, 24, 48, 72, 120, or 336 h after injury muscles were isolated and studied for indexes of muscle function, injury, phagocyte infiltration, and protein metabolism. A group of mice were administered anti-polymorphonuclear cell and anti-macrophage antisera in an attempt to reduce phagocytic infiltration into injured muscle. Force production in extensor digitorum longus muscles was reduced 55% immediately after injury induction and did not recover significantly until 120 h postinjury (28% below baseline). However, rates of protein degradation were not elevated until 48 h postinjury (60% above normal) and were not correlated with the changes in force production (r = -0.37; P = 0.24). Phagocytic infiltration was evident 24-120 h postinjury and was correlated with the elevated protein degradation rates (r = 0.75; P < 0.01). Protein synthesis rates began to increase approximately 48 h after injury was induced and were elevated by 83% 5 days postinjury. Fourteen days after injury, muscle protein degradation and synthesis rates had returned to normal, as well as specific force production, and phagocytic infiltration was not detected. However, muscle mass, protein content, and absolute force production were lower than normal. Antisera-treated mice were rendered neutropenic, but there was no difference in any variable measured between muscles from these mice and muscles from normal mice.

Animals↗

PubMed1994

Eccentric contraction-induced injury of mouse soleus muscle: effect of varying [Ca2+]o.

The objective of this study was to determine the effect of varying extracellular Ca2+ concentration ([Ca2+]o) on eccentric contraction-induced muscle injury. Isolated mouse soleus muscles (n = 64) performed either 20 eccentric or 20 isometric contractions over a 40-min period in a Krebs buffer containing 0.5, 1.25, or 5.0 mM Ca2+. Measurements of contractile function and lactate dehydrogenase accumulation in the buffer were then made every 15 min for 2 h. Prostaglandin E2, leukotriene B4, and tyrosine accumulation in the incubation medium and total muscle [Ca2+] were measured at the end of the experiment. Reductions in maximal isometric tetanic force for muscles immediately after performance of 20 eccentric and 20 isometric contractions were 21.1 +/- 1.4 and 1.2 +/- 0.7%, respectively. Total muscle [Ca2+] was 28-37% higher in muscles that performed eccentric contractions than in those that performed isometric contractions. However, estimates made with a confocal laser scanning microscope and fluo 3 do not indicate that there was a difference in free cytosolic [Ca2+] between fibers from injured and control muscles. Also, leukotriene B4, prostaglandin E2, and tyrosine accumulation in the buffer from muscles that performed eccentric contractions was not elevated over that from muscles that performed isometric contractions. Furthermore, lactate dehydrogenase accumulation and reductions of contractile function over the 2-h incubation period were not enhanced by higher [Ca2+]o or influenced by the type of contraction. These findings suggest that muscles that were injured by eccentric contractions were able to buffer the increased influx of extracellular Ca2+, maintain a normal free cytosolic [Ca2+], and avoid activation of Ca(2+)-sensitive degradative pathways.

Aniline Compounds↗

PubMed1994

Eccentric contraction-induced injury in normal and hindlimb-suspended mouse soleus and EDL muscles.

The primary objective of this study was to compare the magnitude of injury in mouse extensor digitorum longus (EDL) and soleus muscles induced by high-force eccentric contractions. A second objective was to study the effect of altering the daily loading of the muscles through hindlimb suspension (HS) on the injury. One of two protocols was performed in vitro: 1) 15 eccentric contractions (n = 20: 10 EDL and 10 soleus muscles) or 2) 15 isometric contractions (n = 20: 10 EDL and 10 soleus muscles). After the protocol, the decrements in contractile performance and lactate dehydrogenase (LDH) release were measured at 15-min intervals over 1 h. Immediately after the eccentric contraction protocol, markedly greater decrements in maximal isometric tetanic force (Po) occurred in the normal EDL than in the normal soleus muscles (60.7 +/- 4.2 vs. 7.6 +/- 2.1%, P < or = 0.0001). LDH release immediately after the eccentric contraction protocol was 2.7-fold greater in the normal EDL than in the normal soleus muscles. To investigate the role of recent loading of the muscles in the injury, EDL (n = 9) and soleus (n = 10) muscles from mice subjected to HS for 14 days performed the eccentric contraction protocol. HS resulted in greater decrements in contractile performance for the soleus muscles (decreases in Po immediately after the protocol for HS and normal soleus muscles were 31.0 +/- 1.8 and 7.6 +/- 2.1%, respectively; P < or = 0.0001) but not for the EDL muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Mechanical factors in the initiation of eccentric contraction-induced injury in rat soleus muscle.

1. Mechanical factor(s) associated with the initiation of eccentric contraction-induced muscle injury were investigated in isolated rat soleus muscles (n = 180; 42 protocols with 4-6 muscles per protocol). Five eccentric contractions were performed with 4 min between contractions. Three levels of peak eccentric contraction force (100, 125 and 150% of pre-injury maximal isometric tetanic tension, P0), length change (0.1, 0.2 and 0.3 muscle length, L0) and lengthening velocity (0.5, 1.0 and 1.5 L0/s) were utilized. Force was varied with stimulation frequency (10-150 Hz). The eccentric contractions were initiated at muscle lengths of 0.85 or 0.90 L0. Following the fifth eccentric contraction, the muscle was incubated in Krebs-Ringer buffer for 60 min. Peak isometric twitch tension (PT), P0, maximal rate of tension development (+ dP/dt), maximal rate of relaxation (-dP/dt), and creatine kinase (CK) release were measured prior to the five eccentric contractions and at 15 min intervals during the incubation period. Total muscle [Ca2+] was measured after 60 min incubation. 2. The mean (+/- S.E.M.) initial decline in P0 for the muscles performing the most injurious protocol was 13.6 +/- 4.8% (n = 6); P0 in control muscles immediately following performance of five isometric contractions was elevated 1.2 +/- 1.0% (n = 8). These means were different at probability, p = 0.005. Mean [ATP] in muscles immediately following the isometric control and most injurious protocols, respectively, were 16.30 +/- 1.49 and 19.84 +/- 1.38 mumol/g dry wt (p = 0.229). 3. Decrements in P0, PT, +dP/dt, and -dP/dt immediately after the injury protocol were related most closely to the peak forces produced during the eccentric contractions; greater initial declines in P0, +dP/dt and -dP/dt were also observed at higher lengthening velocities independent of peak force. Slow declines in P0 and -dP/dt during the 60 min incubation following the injury protocol were greatest for muscles performing contractions at the longer initial length. CK release was independent of all mechanical factors with the exception of lengthening velocity. CK activity at 45 and 60 min into the incubation period was greater for muscles lengthened at the highest velocity used (1.5 L0/s). Mean total muscle [Ca2+] for muscles performing the eccentric contractions was elevated by 38% over isometric control muscles but the elevation was unrelated to any of the four mechanical factors. 4. These data support the hypothesis that eccentric contraction-induced injury is initiated by mechanical factors, with muscle tension playing the dominant role.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Materials fatigue initiates eccentric contraction-induced injury in rat soleus muscle.

1. The initiation of exercise-induced muscle injury is thought to be the result of high tensile stresses produced in the muscle during eccentric contractions. Materials science theory suggests that high tensile stresses could initiate the injury during the first eccentric contraction (normal stress theory) or after multiple eccentric contractions (materials fatigue). It was the objective of this study to investigate the two possibilities. 2. Rat soleus muscles (n = 66; 11 protocols with 6 muscles per protocol) were isolated, placed in an oxygenated Krebs-Ringer buffer at 37 degrees C, and baseline measurements were made. The muscle then performed an injury protocol which consisted of between zero and ten eccentric contractions (muscle starting length = 0.90 soleus muscle length, L0; length change = 0.25 L0; velocity = 1.5 L0/s; peak force = 180% maximal isometric tetanic tension (P0); time between contractions = 4 min; total duration of the injury protocol = 40 min). At the end of the injury protocol, the muscle was incubated in buffer for 1 h; every 15 min, an isometric twitch and tetanus were performed and lactate dehydrogenase (LDH) release was measured. Total muscle [Ca2+] was measured at the end of the incubation. 3. Change-point regression analysis indicates that at 0 min into the incubation, declines in P0, maximal rate of tension development (+dP/dt), maximal rate of relaxation (-dP/dt), and muscle stiffness (dP/dx) became significantly greater after eight eccentric contractions (p < or = 0.05). No relation was found between the number of eccentric contractions performed and the LDH activity at 0 min into the incubation, although after 60 min of incubation, LDH activity in the buffer was linearly related to eccentric contraction number (p = 0.01). There was no relationship between total muscle [Ca2+] and eccentric contraction number. These findings support the materials fatigue hypothesis of exercise-induced muscle injury.

Animals↗

PubMed1993

Excitation failure in eccentric contraction-induced injury of mouse soleus muscle.

1. Histological evidence suggests that the force deficit associated with eccentric contraction-induced muscle injury is due to structural damage to contractile elements within the muscle fibre. Alternatively, the force deficit could be explained by an inability to activate the contractile proteins. It was the objective of this study to investigate the latter possibility. 2. Mouse soleus muscles were isolated, placed in an oxygenated Krebs-Ringer buffer at 37 degrees C, and baseline measurements were made. The muscle then performed one of three contraction protocols: (1) twenty eccentric (n = 10 muscles); (2) ten eccentric (n = 12); or (3) twenty isometric (n = 10) contractions. At the end of the injury protocol, measurements were made during performance of a passive stretch, twitch and tetanus. Next, force was recorded during exposure of the muscle to buffer containing 50 mM caffeine. 3. Decrements in maximal isometric tetanic force (P0) observed for muscles in the twenty eccentric, ten eccentric, and twenty isometric contraction protocols were 42.6 +/- 4.2, 20.0 +/- 2.3 and 3.9 +/- 2.4%, respectively. However, the caffeine-elicited forces in muscles from the three protocols were not different when corrected for initial differences in P0 (64.9 +/- 1.3, 64.2 +/- 2.1 and 68.9 +/- 2.5% of pre-injury P0). The peak caffeine-elicited force was 118.4 +/- 8.6% of post-injury P0 for the muscles in the twenty eccentric contraction protocol, which was significantly different from that observed for the other protocols (71.8-80.2% post-injury P0). These findings indicate that the force deficit in this muscle injury model results from a failure of the excitation process at some step prior to calcium (Ca2+) release by the sarcoplasmic reticulum. 4. In an attempt to locate the site of failure, intracellular measurements were made in injured muscles to test whether injury to the sarcolemma might have resulted in a shift of the resting membrane potential of the muscle fibre. However, microelectrode measurements of resting membrane potential for muscles in the twenty eccentric contraction protocol (-74.4 +/- 0.6 mV) were not different from muscles in the twenty isometric contraction protocol (-73.4 +/- 1.0 mV). These data suggest that membrane resting conductances were normal and are compatible with the idea that the ability of the injured fibres to conduct action potentials was probably not impaired.

Action Potentials↗

PubMed1991

Mechanisms of exercise-induced muscle fibre injury.

Exercise for which a skeletal muscle is not adequately conditioned results in focal sites of injury distributed within and among the fibres. Exercise with eccentric contractions is particularly damaging. The injury process can be hypothesised to occur in several stages. First, an initial phase serves to inaugurate the sequence. Hypotheses for the initial event can be categorised as either physical or metabolic in nature. We argue that the initial event is physical, that stresses imposed on sarcolemma by sarcomere length inhomogeneities occurring during eccentric contractions cause disruption of the normal permeability barrier provided by the cell membrane and basal lamina. This structural disturbance allows Ca++ to enter the fibre down its electrochemical gradient, precipitating the Ca++ overload phase. If the breaks in the sarcolemma are relatively minor, the entering Ca++ may be adequately handled by ATPase pumps that sequester and extrude Ca++ from the cytoplasm ('reversible' injury). However, if the Ca++ influx overwhelms the Ca++ pumps and free cytosolic Ca++ concentration rises, the injury becomes 'irreversible'. Elevations in intracellular Ca++ levels activate a number of Ca(++)-dependent proteolytic and phospholipolytic pathways that are indigenous to the muscle fibres, which respectively degrade structural and contractile proteins and membrane phospholipids; for instance, it has been demonstrated that elevation of intracellular Ca++ levels with Ca++ ionophores results in loss of creatine kinase activity from the fibres through activation of phospholipase A2 and subsequent production of leukotrienes. This autogenetic phase occurs prior to arrival of phagocytic cells, and continues during the inflammatory period when macrophages and other phagocytic cells are active at the damage site. The phagocytic phase is in evidence by 2 to 6 hours after the injury, and proceeds for several days. The regenerative phase then restores the muscle fibre to its normal condition. Repair of the muscle fibres appears to be complete; the fibres adapt during this process so that future bouts of exercise of similar type, intensity, and duration cause less injury to the muscle.

Body Temperature↗

PubMed1991

Red blood cell pulmonary capillary transit time during exercise in athletes.

The purpose of this study was to test the hypothesis that the exercise-induced hypoxemia observed in endurance athletes is due to a reduction in the mean red blood cell pulmonary capillary transit time consequent to a plateau in pulmonary capillary blood volume (Vc) as exercise intensity progresses from moderate to heavy levels. Measurements of Vc, mean transit time, arterial O2 tension (PaO2), and end tidal-arterial O2 tension difference (AaDO2) were made in 16 subjects (mean maximal oxygen uptake (VO2max) = 4.90 l.min-1) at rest and during five cycle exercise bouts designed to elicit 55, 65, 75, 85, and 95% VO2max. Mean PaO2 fell from 101 mm Hg at rest to 85 mm Hg during heavy exercise. Mean AaDO2 increased linearly from one stage to the next and at the highest work rate equaled 22.3 mm Hg. Mean Vc failed to plateau with increasing exercise intensity and increased on average by 16 ml from one stage to the next. Mean transit time, on average, dropped from 1.05 s at rest to 0.46 s at the lowest work rate. Mean transit time did not decrease further with increasing exercise intensity (range, 0.42-0.46 s). We conclude that, under the conditions of this study, the AaDO2 increases and PaO2 decreases observed in endurance athletes during exercise of increasing intensity is not caused by a plateau in Vc and a consequent reduction in mean transit time.

Adult↗

PubMed1990

Is the gender difference in peak VO2 greater for arm than leg exercise?

Based on observations that the difference between men and women in estimates of arm musculature is greater than the difference in leg musculature, it was hypothesized that the gender difference in peak oxygen uptake (VO2; l.min-1) would be greater for arm exercise than leg exercise. To test this hypothesis, 19 (10 men, 9 women) highly trained swimmers (HT) and 20 (10 men, 10 women) untrained students (UT) were tested for peak VO2 on cycle and arm-crank ergometers. Arm and leg fat-free volumes (FFV) were measured to provide an estimate of muscle distribution. No gender difference was observed in either the arm-to-leg peak VO2 ratio (0.699 for the men vs 0.696 for the women) or in the arm-to-leg FFV ratio (0.410 for the men vs 0.402 for the women). Although the proportion of musculature in the arms as assessed by the FFV appeared to be the same in men and women, the similarity in muscle distribution was probably not responsible for the identical average arm-to-leg peak VO2 ratios. The variance in the muscle distribution accounted for only 2-4% of the variance in the arm-to-leg peak VO2 differences within individuals. We conclude that factors other than arm and leg muscle dimensions account for the variability in the arm-to-leg peak VO2 ratio and that the gender difference in peak VO2 is the same for arm and leg exercise.

Adult↗

PubMed1990

Criterion-referenced standards for youth health-related fitness tests: a tutorial.

A new development in the testing of physical fitness of youth is the use of criterion-referenced standards (CRS). Although three national youth health-related physical fitness (HRPF) tests currently have CRS, a detailed description of the procedures used in their development has not been published nor have the standards been validated. Consequently, the scientific basis of these standards has been questioned. The purposes of this tutorial are (a) to discuss briefly issues related to the development of CRS for HRPF tests, (b) to provide a detailed description of procedures used in development of mile run/walk test CRS as an example, and (c) to illustrate how these standards can be validated. The objective is to stimulate discussion and critical evaluation of CRS for youth HRPF tests.

Adolescent↗

PubMed1989

Does lung function limit performance in a 24-hour ultramarathon?

Based on observations of impaired lung function after marathon and ultramarathon running, it was hypothesized that the decline in running speed during a 24-h ultramarathon may be explained, in part, by ventilatory muscle fatigue. To test this hypothesis, ten competitors in the 1988 TAC/USA National 24-h Championship performed a battery of pulmonary function tests every 3 h during the race. The tests included measurement of inspiratory capacity, peak flow, forced vital capacity, forced expiratory volume in 1 sec, maximum voluntary ventilation for 12 sec (MVV12), and maximal respiratory pressures. Running speed was averaged over 3-h periods. MVV12 was significantly decreased (17%), but only after 24 h of running. All other ventilatory measures tended to decrease over time but the changes were not significant. However, after correcting for between-subject differences in running speed, the variance in MVV12 accounted for 39% (P less than 0.0001) of the variance in running speed. It was concluded that the decrease in ventilatory muscle endurance may constrain running speed in extremely prolonged running events.

Adult↗

PubMed1989

Modeling the effect of alterations in hemoglobin concentration on VO2max.

Studies investigating the effects of experimental alterations in hemoglobin concentration on VO2max have been equivocal. The objectives of this study were: 1) to develop a comprehensive model of the oxygen transport system based on a lumped parameter model of the cardiovascular system and 2) to test the new model's ability to predict VO2max changes observed in studies that have manipulated [Hb]. The resulting model demonstrates that blood volume changes that accompany venesection or blood doping may account for the apparent lack of a consistent [Hb]:VO2max relationship. A 1 l drop in blood volume is predicted to reduce VO2max by approximately 20%. A decrease in hemoglobin concentration of 2.6 g.dl-1 is needed to achieve a similar decrement. The accuracy of the model in predicting VO2max changes was tested by comparing the variance of the differences between predicted and observed changes in 19 studies with the total within-subject variance for VO2max measurement. This analysis indicates that there was no significant difference between the changes in VO2max observed and those predicted if a measurement error of 6.3% or greater was assumed. Analysis of data in the literature using our modified lumped parameter model reinforces those studies that have found VO2max changes to parallel changes in total body hemoglobin. The model developed is potentially useful for more accurately predicting changes in VO2max from alterations in hemoglobin concentration and/or blood volume.

Animals↗