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Biomedical subjects

R A Herb

Publications and source records attributed to R A Herb.

16 recordsLinked to original sources

Mechanism of specific force deficit in the senescent rat diaphragm.

Aging is associated with a decline in the maximal in vitro specific force in the rat costal diaphragm. The purpose of this study was to determine if this force deficit is associated with a decrease in the concentration of myofibrillar protein in diaphragm fibers of senescent rats. Isometric twitch and tetanic contractile properties were measured on diaphragm strips from young adult (9-month-old: n = 12) and senescent (26-month-old: n = 13) male specific pathogen free-barrier protected Fischer 344 rats. Maximal tetanic force (Po) normalized to the cross-sectional area (CSA) of the in vitro diaphragm strips was 16.4% lower in the senescent diaphragms (21.03 +/- 0.4 N/cm2) compared to the young adult (25.16 +/- 0.5 N/cm2) (p < 0.001). Diaphragm water content was significantly higher in the senescent group (75.9% of total wet mass) compared to the young adult (72.1% of total wet mass, p < 0.05). Subtracting the contribution of water from the CSA of the diaphragm strips significantly reduced (p < 0.05) the senescent specific Po deficit (from -16.4 to -6.4%). Further, correcting Po for the contribution of myofibrillar protein to CSA resulted in no age group differences in specific force. These data indicate that the age-related decline in diaphragm in vitro maximal specific Po can be explained by an age-related increase in the water content of the diaphragm muscle. Future experiments are necessary to determine the mechanism(s) responsible for this observation.

Aging

Clenbuterol-induced fiber type transition in the soleus of adult rats.

This study examined the effects of 6 weeks of treatment with the beta(2)-adrenoceptor agonist, clenbuterol, on the soleus muscle of adult female Sprague-Dawley rats. Animals (4 months old) were divided into two groups: clenbuterol treated (CL, n = 7) (2 mg.kg-1 body mass injected subcutaneously every other day), and control (CON, n = 7) (injected with isotonic saline). Post-treatment body weights were approximately 5% greater in the CL group compared to CON (P < 0.05). Polyacrylamide gel electrophoresis (SDS-PAGE) of soleus myofibrillar protein indicated a clenbuterol-induced decrease (P < 0.05) in the relative percentage of type I myosin heavy chain (MHC) with a concomitant increase (P < 0.05) in type IIdx MHC, while the proportion of type IIa MHC was unaffected. ATPase fiber typing revealed increases (P < 0.05) in the proportion of type II fibers expressed both as a percentage of total fiber number and total cross-sectional area (CSA). Finally, mean type II fiber CSA was approximately 25% greater (P < 0.05) in the CL groups as compared to the CON group. These data indicate that clenbuterol treatment results in alterations in the MHC phenotype and an increased proportion of type II fiber CSA in the soleus of adult rats. These observations were due to an increase in the total number of type II fibers, as well as hypertrophy of these fibers. Thus, the relative increase in the number of histochemically determined type II fibers and the emergence of the normally unexpressed type IIdx MHC isoform in the soleus suggest a clenbuterol-induced transition of muscle fiber phenotype as well as selective hypertrophy of the type II fibers.

Adrenergic beta-Agonists

Age-related increases in diaphragmatic maximal shortening velocity.

Recent evidence demonstrates that aging results in an increase in fast (type IIB) myosin heavy chain (MHC) in the rat diaphragm. It is unknown whether this age-related change in fast MHC influences the diaphragmatic maximal shortening velocity (Vmax). Therefore, we tested the hypothesis that aging is associated with an increase in the diaphragmatic Vmax and that the increase in the Vmax is highly correlated with the percentage of type IIb MHC. In vitro contractile properties were measured with costal diaphragm strips obtained from young (4 mo old; n = 8) and (old 24 mo old; n = 8) male Fischer-344 rats. Diaphragmatic maximal tetanic specific force production was 14.5% lower in the old compared with the young animals (23.0 +/- 0.4 vs. 19.7 +/- 0.8 N/cm2; P < 0.05). In contrast, the diaphragmatic Vmax was significantly higher in the old compared with the young animals (5.5 +/- 0.1 vs. 4.4 +/- 0.3 lengths/s; P < 0.05). Although the percent type IIb MHC was significantly higher (approximately +14%; P < 0.05) in the old compared with the young animals, the correlation between Vmax and percent type IIb MHC was relatively low (r = 0.50; P > 0.05). These data support the hypothesis that an age-related increase in diaphragmatic Vmax occurs; however, factors in addition to type IIb MHC are involved in regulating diaphragmatic Vmax. Interestingly, although aging resulted in a decrease in diaphragmatic maximal specific force production, power output at all muscle loads was maintained in the old animals due to the increase in diaphragmatic shortening velocity.

Aging

Alterations in phenotypic and contractile properties of the rat diaphragm: influence of hypothyroidism.

This study examined the influence of experimental hypothyroidism on myosin isoform distribution and contractile function of the costal diaphragm. Adult female Sprague-Dawley rats were randomly assigned to control (n = 12) or hypothyroid groups (n = 13) over a 6-wk treatment period. In comparison to the control group, in the hypothyroid group the relative distribution of type I myosin heavy chain (MHC) was increased 35% (P < 0.05), whereas type IIb MHC decreased 63% (P < 0.05). Similarly, Ca(2+)-activated myosin adenosinetriphosphatase activity (nmol Pi.mg-1.min-1) in the hypothyroid group was reduced 30% compared with the control group (P < 0.05). Furthermore, significant reductions in diaphragmatic maximal tetanic specific tension (Po; N.cm-2; -21%) and maximal shortening velocity (Vmax; muscle length/s; -25%) were observed in the hypothyroid group. These data provide the first evidence that hypothyroid produces a fast-(type IIb) to-slow (type I) shift in costal diaphragmatic MHC isoform profile that is highly correlated to the observed decrease in Vmax. Finally, the present findings indicate that hypothyroidism does not alter myofibrillar content or noncontractile elements of the diaphragm, thereby suggesting an alternative mechanism(s) to explain the reduction in specific Po.

Animals

The effects of hypothyroidism on single fibers of the rat soleus muscle.

Skinned single fibers were used to test the hypothesis that skinned fibers from hypothyroid soleus muscle would have a higher sensitivity to calcium compared with control fibers, as indicated by a leftward shift of the pCa-force curve. Control rats (n = 14) received sham injections, while the hypothyroid group (n = 16) received thyroidectomy and a 6-week injection period of the antithyroid drug 6-n-propyl-2-thiouracil. Hypothyroidism caused the type I fiber number to increase significantly (11%) in the soleus. Hypothyroid fibers produced 16% less absolute tension than control fibers. However, cross-sectional areas of control fibers were significantly greater (25%) than those of hypothyroid fibers, so that when force was normalized to cross-sectional area, no differences between groups existed. Calcium requirement for half-maximal force production (pCa50) did not differ, but the slope of the pCa-force curve was different between groups. These data suggest that hypothyroidism did not alter the intrinsic force-generating capacity of the soleus muscle fibers. Thus, alterations in hypothyroid soleus contractile function seen in vitro may be explained by alterations in excitation-contraction coupling and (or) shifts in muscle fiber types.

Animals

Role of beta-adrenergic mechanisms in exercise training-induced metabolic changes in respiratory and locomotor muscle.

To test the hypothesis that beta-adrenergic stimulation is required for the normal increase in oxidative capacity of respiratory and locomotor skeletal muscle in response to exercise training, we examined the effects of beta-blockade on muscle oxidative capacity in trained and sedentary rats. Thirty-four female adult Sprague-Dawley rats were randomly divided into four experimental groups: 1) trained+propranolol (TP); 2) trained + sham injection (TS); 3) sedentary + propranolol (SP); and 4) sedentary + sham injection (SS). Training increased (p < 0.05) citrate synthase (CS) activity in the plantaris (+29%) and costal diaphragm (+12%) of TS animals compared to SS animals. In contrast, training did not (p > 0.05) increase costal diaphragm CS activity in TP animals compared to the SS group. Further, although training increased (p < 0.05) plantaris CS activity in the TP group (+18%) compared to the SP group, the training-induced increase in muscle CS activity was 11% lower (p < 0.05) than observed in TS animals. Collectively, these results suggest that beta-adrenergic mechanisms may play a role in the normal training-induced increase in oxidative capacity in both respiratory and locomotor skeletal muscles.

Adaptation, Physiological

Lactic acidosis and diaphragmatic function in vitro.

Diaphragm fatigue occurs during heavy exercise. Acidosis leads to skeletal muscle fatigue, yet the diaphragm is not a net producer of either lactic acid or hydrogen ions. We tested the hypothesis that hydrogen ion and lactic acid concentrations similar to those seen in arterial blood at maximal exercise decrease contractility of the in vitro isolated rat diaphragm. Diaphragm strips were exposed to a control solution for 15 min and then to one of the following treatment solutions: control (C, pH = 7.4) or 10 mM lactic acid buffered to pH 7.4 (L74), pH 7.2 (L72), pH 7.1 (L71), or pH 6.8 (L68). After 15 min, the force-frequency relationship of the strip was measured. The strips were then stressed with 75 contractions at 25 Hz (250-ms train duration) at the rate of one per second and the force-frequency curve was measured after 15 min of recovery. The L74, L72, and L71 strips responded similarly to the C strips at all times and frequencies. Decrements in force associated with acidosis were only seen in L68. Within L68, we found decreases in force at stimulation frequencies < 100 Hz. These data suggest that physiologic levels of exogenous hydrogen ions are not a primary cause of in vitro diaphragm fatigue.

Acidosis, Lactic

Regional training-induced alterations in diaphragmatic oxidative and antioxidant enzymes.

We examined the relationship between the intensity and duration of exercise training and the up-regulation of diaphragmatic oxidative and antioxidant enzyme activities. Nine groups of rats exercised for 10 weeks (4 days/week). Groups of animals exercised at three intensities (low, moderate, and high); at each exercise intensity, a group of animals ran at one of three exercise durations (30, 60, and 90 min/day). Sedentary animals served as controls. Muscle oxidative capacity was assessed by citrate synthase (CS) activity while antioxidant capacity was evaluated by total superoxide dismutase (SOD) and total glutathione peroxidase (GPX) activities. All intensities and durations of exercise training promoted significant (P < 0.05) increases in costal diaphragmatic CS, SOD, and GPX activities. Increases in costal CS, SOD, and GPX activity were independent of the exercise intensity and duration. High and moderate intensity exercise of 90 min duration significantly elevated (P < 0.05) crural diaphragm CS activity. Further, high and moderate intensity exercise of durations > or = 60 min promoted significant (P < 0.05) increases in crural diaphragm SOD activities. Exercise did not influence (P > 0.05) crural diaphragm GPX activity. We conclude that the training threshold for up-regulation of oxidative and antioxidant enzyme activities differs between the costal and crural diaphragm.

Animals

Influence of exercise and fiber type on antioxidant enzyme activity in rat skeletal muscle.

These experiments examined the influence of exercise intensity and duration on antioxidant enzyme activity in locomotor muscles differing in fiber type composition. Nine groups of female Sprague-Dawley rats (age 120 days) exercised 4 days/wk on a motor-driven treadmill for 10 wk. The impact of three levels of exercise intensity (low, moderate, and high: approximately 55, approximately 65, and approximately 75% of maximal oxygen consumption, respectively) and exercise duration (30, 60, and 90 min/day) was assessed. Sedentary animals served as controls. Oxidative capacity in the soleus and white and red gastrocnemius was assessed by measurement of citrate synthase (CS) activity, and antioxidant capacity was evaluated by assay of total superoxide dismutase, catalase, and total glutathione peroxidase (GPX) activities. In all muscles, CS activity increased as a function of exercise duration. Furthermore, in the soleus and white gastrocnemius, the magnitude of the training-induced increase in CS activity was directly related to exercise intensity. In contrast, the peak increase in CS activity in the red gastrocnemius was relatively independent of exercise intensity. Catalase activity was not increased (P > 0.05) in any muscle with training. Training-induced changes in superoxide dismutase and GPX activities were muscle specific; specifically, exercise training significantly (P < 0.05) increased superoxide dismutase activity in the soleus as a function of exercise duration up to 60 min/day. Conversely, training-induced significant (P < 0.05) increases in GPX activity occurred in red gastrocnemius only; the magnitude of the GPX increase was directly related to exercise duration but relatively independent of intensity. These data demonstrate that exercise training-induced changes in muscle antioxidant enzymes are muscle specific.

Animals

Metabolic characteristics of primary inspiratory and expiratory muscles in the dog.

These experiments examined the metabolic properties of the canine respiratory muscles. Because the costal diaphragm (COD), crural diaphragm (CRD), parasternal intercostals (PI), triangularis sterni (TS), and transversus abdominis (TA) are active during quite breathing in the dog, we hypothesized that these muscles would have different metabolic profiles (i.e., higher oxidative and antioxidant enzyme activities) compared with ventilatory muscles recruited only at increased ventilatory requirements [e.g., scalene (SC) and external oblique (EO)] and locomotor muscles [e.g., deltoid (DEL)]. To test this hypothesis, muscle samples were removed from six healthy adult dogs and analyzed to determine the activities of citrate synthase (CS), phosphofructokinase (PFK), 3-hydroxyacyl-CoA dehydrogenase (HADH), and superoxide dismutase (SOD). The activities of these enzymes were interpreted as relative measures of metabolic capacities, and enzyme activity ratios were considered as representing relationships between different metabolic pathways. Analysis revealed that CS and HADH activities were significantly higher (P < 0.05) in the PI, COD, CRD, and TS compared with those in all other muscles. Muscles with the lowest CS, HADH, and SOD activities (i.e., SC, TA, EO, DEL) generally had the highest PFK activities, Furthermore, the PFK/CS ratio was significantly lower in the PI, COD, CRD, and TS compared with that in all other muscles studied. These data support the notion that the canine PI, COD, CRD, and TS are metabolically different from other key ventilatory muscles.

3-Hydroxyacyl CoA Dehydrogenases

Rigorous exercise training increases superoxide dismutase activity in ventricular myocardium.

Controversy exists as to the effect of endurance training on myocardial antioxidant enzyme activity. These experiments sought to clarify this issue by examining antioxidant enzyme activities in the rat ventricular myocardium in response to different intensities and durations of exercise training. Female Fischer-344 rats (120 days old) were assigned to either a sedentary control group or one of nine exercise training groups. Animals were exercised on a motorized treadmill for 10 wk; combinations of three durations (30, 60, and 90 min/day), and three levels of exercise intensity (low, moderate, and high) were studied. Exercise training did not alter (P > 0.05) citrate synthase, catalase, or glutathione peroxidase activities in the right or left ventricle. In contrast, high-intensity exercise (all durations) and moderate-intensity exercise (90 min/day) resulted in a significant increase (P < 0.05; +28-30%) in right ventricular superoxide dismutase (SOD) activity. Similarly, high-intensity exercise training (all durations) resulted in a significant elevation (P < 0.05; +14-26%) of left ventricular SOD activity. Furthermore, low- and moderate-intensity exercise training of long duration (i.e., 60-90 min/day) resulted in significant increases (P < 0.05; +10-23%) in left ventricular SOD activity. These data support the hypothesis that high-intensity exercise (> or = 30 min/day) or moderate-intensity exercise of long duration (> or = 60 min/day) is effective in upregulating SOD activity in the ventricular myocardium.

Animals

Exercise and glucocorticoid-induced diaphragmatic myopathy.

We tested the hypothesis that a chronically active muscle, such as the rat diaphragm, would be more resistant to glucocorticoid-induced myopathy than a less active locomotor skeletal muscle (plantaris). Furthermore, we sought to determine whether endurance exercise could antagonize the glucocorticoid-induced atrophy in the diaphragm. Rats were assigned to one of seven experimental groups (n = 10 per group) and injected daily over a 10-day period with either a sham solution or prednisolone acetate: group 1: control; sedentary and sham injected; group 2: control; exercise trained and sham injected; group 3; sedentary; prednisolone (0.5 mg.kg-1 x day-1); group 4: sedentary; prednisolone (1.0 mg.kg-1 x day-1); group 5: sedentary; prednisolone (2.0 mg.kg-1 x day-1); group 6: sedentary; prednisolone (5.0 mg.kg-1 x day-1); group 7: exercise trained; prednisolone (5.0 mg.kg-1 x day-1). Slope differences in the dose-response curves suggest that prednisolone-induced muscle atrophy in the plantaris was more severe than that in the diaphragm. Furthermore, high doses of prednisolone resulted in a differential effect on muscle bioenergetic enzyme activities in the plantaris and diaphragm. Prednisolone treatment (> or = 2 mg.kg-1 x day-1) resulted in a significant reduction in phosphofructokinase activity (expressed as microM substrate.min-1 x mg protein-1) and an increase in 3-hydroxyacyl-CoA dehydrogenase activity in the plantaris muscle. In contrast, prednisolone treatment did not influence phosphofructokinase activity (P > 0.05) in the diaphragm but decreased (P < 0.05) relative citrate synthase activity. Finally, 90 min daily of endurance exercise did not antagonize prednisolone-induced myopathy in either the diaphragm or the plantaris.

Adrenal Glands

Caffeine and exercise performance. An update.

Three principal cellular mechanisms have been proposed to explain the ergogenic potential of caffeine during exercise: (a) increased myofilament affinity for calcium and/or increased release of calcium from the sarcoplasmic reticulum in skeletal muscle; (b) cellular actions caused by accumulation of cyclic-3',5'-adenosine monophosphate (cAMP) in various tissues including skeletal muscle and adipocytes; and (c) cellular actions mediated by competitive inhibition of adenosine receptors in the central nervous system and somatic cells. The relative importance of each of the above mechanisms in explaining in vivo physiological effects of caffeine during exercise continues to be debated. However, growing evidence suggests that inhibition of adenosine receptors is one of the most important, if not the most important, mechanism to explain the physiological effects of caffeine at nontoxic plasma concentrations. Numerous animal studies using high caffeine doses have reported increased force development in isolated skeletal muscle in both in vitro and in situ preparations. In contrast, in vivo human studies have not consistently shown caffeine to enhance muscular performance during high intensity, short term exercise. Further, recent evidence supports previous work that shows caffeine does not improve performance during short term incremental exercise. Although controversy exists, the major part of published evidence evaluating performance supports the notion that caffeine is ergogenic during prolonged (> 30 min), moderate intensity (approximately 75 to 80% VO2max) exercise. The mechanism to explain these findings may be linked to a caffeine-mediated glycogen sparing effect secondary to an increased rate of lipolysis.

Animals

Effect of including parents in a school-based exercise and nutrition program for children.

The purpose of this study was to examine the effect of parental involvement in a school-based program about exercise and nutrition. One fifth grade and one sixth grade class were randomly assigned to each of the three different treatment conditions, a school-and-home condition (n = 45), a school-only condition (n = 43), and a control condition (n = 44). In the school-and-home condition, the children's parents were also asked to participate in nutritional and exercise activities at home as a family "home team." A multivariate analysis of variance on change scores was completed on the following variables: height, weight, skinfold, sit-and-reach, sit-ups, mile run, exercise knowledge, saturated fat, cholesterol, percent calories from fat, percent calories from carbohydrates, and nutrition knowledge. There was a significant difference among groups. The school-and-home and school-only groups showed significantly greater improvement than the control group but were not significantly different from each other. Univariate analyses on posttest scores indicated that the school-and-home children scored significantly higher than the control group on sit-and-reach flexibility and nutrition knowledge. The results indicate that including the family was primarily effective in facilitating children's improvements in flexibility and nutrition knowledge rather than in diet and exercise behaviors.

Child

Anabolic steroids and aggressive behavior in cynomolgus monkeys.

An animal model was employed to examine the effect of testosterone on aggressive behavior patterns. Ten cynomolgus monkeys were assigned to either an experimental or a control group and given biweekly injections; the experimental group received testosterone propionate, and the controls a sham solution. Prior to and upon the completion of an 8-week treatment period, behavioral observations were conducted. Although the administration of testosterone resulted in a significant increase in aggression, more important was the finding that changes in behavior were mediated by social status; that is, the incidence of both contact and noncontact aggression in dominant monkeys was far greater than the frequency of these behaviors in subordinate monkeys. These data are discussed in terms of the potential role of anabolic steroids as a risk factor in cardiovascular disease.

Aggression

The role of anabolic steroids on baseline and stress heart rate in cynomolgus monkeys.

This investigation examined the role of anabolic steroids on baseline heart rate (HR) and HR responses to the threat of capture in Macaca fascicularis. Ten cynomolgus monkeys were randomly assigned either to a steroid or to a sham control group. Steroid-treated animals were given testosterone injections biweekly for 10 weeks, whereas sham controls received injections of sesame oil on an identical schedule. Pretreatment and posttreatment HRs were evaluated to establish both baseline and acute-stress responses. Results revealed that animals given testosterone experienced a statistically significant increase in baseline HR when contrasted with the sham controls. No difference between the groups was detected in response to the threat of capture.

Animals