Intermittent hyperthermia enhances skeletal muscle regrowth and attenuates oxidative damage following reloading.

Skeletal muscle reloading following disuse is characterized by profound oxidative damage. This study tested the hypothesis that intermittent hyperthermia during reloading attenuates oxidative damage and augments skeletal muscle regrowth following immobilization. Forty animals were randomly divided into four groups: control (Con), immobilized (Im), reloaded (RC), and reloaded and heated (RH). All groups but Con were immobilized for 7 days. Animals in the RC and RH groups were then reloaded for 7 days with (RH) or without (RC) hyperthermia (41-41.5 degrees C for 30 min on alternating days) during reloading. Heating resulted in approximately 25% elevation in heat shock protein expression (P < 0.05) and an approximately 30% greater soleus regrowth (P < 0.05) in RH compared with RC. Furthermore, oxidant damage was lower in the RH group compared with RC because nitrotyrosine and 4-hydroxy-2-nonenol were returned to near baseline when heating was combined with reloading. Reduced oxidant damage was independent of antioxidant enzymes (manganese superoxide dismutase, copper-zinc superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase). In summary, these data suggest that intermittent hyperthermia during reloading attenuates oxidative stress and improves the rate of skeletal muscle regrowth during reloading after immobilization.

Botulinum neurotoxin type A causes shifts in myosin heavy chain composition in muscle.

Botulinum neurotoxin type A has gained widespread use for treatment of a host of neuromuscular conditions. However, the potential effect of this toxin has on the histological and biochemical properties of skeletal muscle remains largely unexplored. The purpose of this study was to characterize the myosin heavy chain (MHC) distribution of adult rat skeletal muscle treated with botulinum neurotoxin type. Varying doses of the toxin were injected into the triceps surae muscle group of one hind limb. Force production was assessed periodically to access the functional deficit incurred. After 10 weeks, animals were sacrificed, muscles removed, and MHC composition determined. Body weight, muscle weight and force of the injected leg were significantly reduced in all groups, while loss of muscle weight and force in the contralateral leg was variable. In the injected plantaris and gastrocnemius muscles, type I MHC increased approximately 100%, while type IIa/x decreased approximately 50%. In the contralateral gastrocnemius, types I and IIa/x MHC increased approximately 100%, while type IIb decreased approximately 45%. These data suggest that botulinum neurotoxin causes shifts in MHC composition in injected and contralateral muscles that are contrary to those seen with denervation and similar to those seen with aging.

Oxidative damage to skeletal muscle following an acute bout of contractile claudication.

The purpose of this study was to determine the extent and sources of oxidative stress within skeletal muscle following an acute bout of contractile claudication. Twenty-four hours after unilateral ligation of the femoral artery, rat hind limbs were stimulated in vivo for 30 min, and force production measured. One-hour post-stimulation, animals were sacrificed and soleus and gastrocnemius muscles removed. There was significant reduction in force in the control limb (sham ligated/stimulated (SS)), while force in the ligated limb (ligated/stimulated (LS)) was reduced by 72%. There was an increase in skeletal muscle lipid hydroperoxides (53 and 47%) and protein carbonyls (57 and 54%) in the soleus and gastrocnemius muscles, respectively, and the muscle wet/dry weight ratio was increased in the gastrocnemius muscles. Total glutathione (GHS) was reduced, while xanthine oxidase (XO) activity and neutrophil levels were increased, in LS compared to SS in both soleus and gastrocnemius muscles. These data suggest that an acute bout of contractile claudication causes significant oxidative damage and edema to skeletal muscle. This is associated with both an increase in the activity of the radical-producing enzyme xanthine oxidase and an increase in activated neutrophils.

Increased antioxidant capacity does not attenuate muscle atrophy caused by unweighting.

Previous studies have increased antioxidant capacity in skeletal muscle to attenuate oxidative stress and muscle atrophy during limb immobilization (Appell HJ, Duarte JAR, and Soares JMC. Int J Sports Med 18: 157-160, 1997; Kondo H, Miura M, Nakagaki I, Sasaki S, and Itokawa Y. Am J Physiol Endocrinol Metab 262: E583-E590, 1992). The purpose of this study was to determine the level of oxidative stress in muscle during hindlimb unweighting (HLU) and whether antioxidant supplementation can attenuate the atrophy and changes in contractile properties resulting from 14 days of unweighting. Muscle unweighting caused a 44% decrease in soleus (Sol) and a 30% decrease in gastrocnemius (GS) mass, a 7% decrease in body weight, and 28% decrease in tetanic force in the GS. Protein carbonyls increased by 44% in the Sol with HLU. Antioxidant supplementation did not attenuate the GS or Sol atrophy or the decrease in GS force generation during HLU. Sol and GS protein concentration was not different between groups. The GS was also subjected to three different oxidative challenges to determine whether the supplement increased the antioxidant capacity of the muscle. In all cases, muscles exhibited an increased antioxidant capacity. These data indicate that antioxidant supplementation was not an effective countermeasure to the atrophy associated with HLU.

Effects of reduced O2 delivery with anemia, hypoxia, or ischemia on peak VO2 and force in skeletal muscle.

This investigation was designed to describe alterations in O2 uptake (VO2) and tension development in a contracting in situ gastrocnemious-plantaris muscle preparation during three conditions of reduced O2 delivery [arterial O2 concentration X blood flow (Q)]. The three conditions, hypoxemia (H), ischemia (I), and anemia (A), were matched for O2 delivery. A normoxic normal flow condition was also utilized for comparison. H was produced by respiring the animals with 9% O2 in N2; I was produced by lowering Q, and A was produced by hemodilution with 6% dextran. The stimulation pattern for the isometric tetanic contractions used was 1 train/s, and each train was 200 ms, 70 Hz, and 6 V. The muscle was maximally contracted during each of the experimental conditions, and the conditions were administered in random order. In each bout the contractions continued for 5 min with 30 min of rest between bouts. Samples of arterial and muscle venous blood were obtained during the last 30 s of each bout. VO2 during I (125 ml.kg-1.min-1) was less than during N (145 ml.kg-1.min-1; P < 0.05) and greater than during H or A (104 and 101 ml.kg-1.min-1, respectively; P < 0.05). Venous PO2 (PVO2) was significantly lower during H (17.1 Torr) compared with the other conditions; no differences existed between N, I, and A (26.8, 26.0, and 28.1 Torr, respectively). Tension development was reduced by the reduction of O2 delivery during I, H, and A compared with N. Tension developed among the reduced O2 delivery groups was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

O2 delivery to contracting muscle during hypoxic or CO hypoxia.

The consequences of a decreased O2 supply to a contracting canine gastrocnemius muscle preparation were investigated during two forms of hypoxia: hypoxic hypoxia (HH) (n = 6) and CO hypoxia (COH) (n = 6). Muscle O2 uptake, blood flow, O2 extraction, and developed tension were measured at rest and at 1 twitch/s isometric contractions in normoxia and in hypoxia. No differences were observed between the two groups at rest. During contractions and hypoxia, however, O2 uptake decreased from the normoxic level in the COH group but not in the HH group. Blood flow increased in both groups during hypoxia, but more so in the COH group. O2 extraction increased further with hypoxia (P less than 0.05) during concentrations in the HH group but actually fell (P less than 0.05) in the COH group. The O2 uptake limitation during COH and contractions was associated with a lesser O2 extraction. The leftward shift in the oxyhemoglobin dissociation curve during COH may have impeded tissue O2 extraction. Other factors, however, such as decreased myoglobin function or perfusion heterogeneity must have contributed to the inability to utilize the O2 reserve more fully.

Responses of innervated and denervated gut to whole-body hypoxia.

As a significant user of O2 at rest (20% of whole body), the gut may be subject to more severe limitation of O2 supply during global hypoxia than more vital areas because of preferential redistribution of blood flow. Accordingly, its accumulation of O2 deficit during hypoxia and its excess O2 use during normoxic recovery might be altered by extrinsic neural activity. We measured blood flow and O2 uptake in whole body (WB) and gut segments while anesthetized dogs were ventilated with 9% O2-91% N2 for 30 min followed by 30-min normoxic recovery. In six dogs extrinsic innervation to the gut segment was left intact and it was severed in another six animals. O2 deficit and excess were the accumulated differences from the normoxic O2 uptake for both gut and WB corrected for O2 stores changes. The intact gut, although only 4% body wt, incurred 22% of WB O2 deficit but contributed only 8% to WB O2 excess. The imbalance (gut excess was only 44% of gut deficit) implied that O2 using functions were curtailed during hypoxia without obligating an energy stores deficit. Denervation did not alter these quantitative relationships. Blood flow responses to transition between normoxia and hypoxia were only transiently altered. Extrinsic innervation apparently plays no major role in gut responses to WB hypoxia.

Muscle O2 deficit during hypoxia and two levels of O2 demand.

We have examined the relative deficits in tension development and O2 uptake in contracting skeletal muscle during severe hypoxic hypoxia. Anesthetized mongrel dogs were ventilated to maintain an end-tidal PCO2 between 35 and 40 Torr. Venous outflow from the gastrocnemius muscle was measured using an electromagnetic flow probe. The tendon was cut and attached to a strain gauge. The muscle was stimulated to contract isometrically at 2 or 4 Hz for 20 min. Hypoxia (9% O2 in N2) was then imposed for 30 min, followed by 30 min of normoxia. Blood flow first increased in proportion to the contraction frequency and then increased further a similar amount in both groups during hypoxia. O2 extraction and blood flow reached maximal levels during hypoxia in the 2-Hz group. The further O2 deficit that was accumulated during 4 Hz and hypoxia was, therefore, a result of the greater discrepancy between O2 supply and demand. O2 uptake decreased more in hypoxia than did developed tension. These results are best explained by ATP supplementation from nonaerobic energy sources that was promoted by the free-flow condition of hypoxic hypoxia.

Systemic and intestinal limits of O2 extraction in the dog.

When systemic delivery of O2 (QO2 = QT X CaO2, where QT is cardiac output and CaO2 is arterial O2 content) is reduced by bleeding, the systemic O2 extraction ratio [ER = (CaO2 - CVO2)/CaO2, where CVO2 is venous O2 content] increases until a critical limit is reached below which O2 uptake (VO2) becomes limited by O2 delivery. During hypovolemia, reflex increases in mesenteric arterial tone may preferentially reduce gut blood flow so that the onset of O2 supply dependence occurs in the gut before other regions. We compared the critical O2 delivery (QO2c) and critical extraction ratio (ERc) of whole body and an isolated segment (30-50 g) of small bowel in seven anesthetized paralyzed dogs ventilated with room air. Systemic QO2 was reduced in stages by controlled hemorrhage as arterial O2 content was maintained, and systemic and gut VO2 and QO2 were measured at each stage. Body QO2c was 7.9 +/- 1.9 ml X kg-1 X min-1 (ERc = 0.69 +/- 0.12), whereas gut O2 supply dependency occurred when gut QO2 was 34.3 +/- 11.3 ml X min-1 X kg gut wt-1 (ERc = 0.63 +/- 0.09). O2 supply dependency in the gut occurred at a higher systemic QO2 (9.7 +/- 2.7) than whole-body QO2c (P less than 0.05). The extraction ratio at the final stage (maximal ER) was less in the gut (0.80 +/- 0.05) than whole body (0.87 +/- 0.06). Thus during reductions in systemic QO2, gut VO2 was maintained by increases in gut extraction of O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Heat stress attenuates skeletal muscle atrophy in hindlimb-unweighted rats.

This study tested the hypothesis that elevation of heat stress proteins by whole body hyperthermia is associated with a decrease in skeletal muscle atrophy induced by reduced contractile activity (i.e. , hindlimb unweighting). Female adult rats (6 mo old) were assigned to one of four experimental groups (n = 10/group): 1) sedentary control (Con), 2) heat stress (Heat), 3) hindlimb unweighting (HLU), or 4) heat stress before hindlimb unweighting (Heat+HLU). Animals in the Heat and Heat+HLU groups were exposed to 60 min of hyperthermia (colonic temperature approximately 41.6 degrees C). Six hours after heat stress, both the HLU and Heat+HLU groups were subjected to hindlimb unweighting for 8 days. After hindlimb unweighting, the animals were anesthetized, and the soleus muscles were removed, weighed, and analyzed for protein content and the relative levels of heat shock protein 72 (HSP72). Compared with control and HLU animals, the relative content of HSP72 in the soleus muscle was significantly elevated (P < 0.05) in both the Heat and Heat+HLU animals. Although hindlimb unweighting resulted in muscle atrophy in both the HLU and Heat+HLU animals, the loss of muscle weight and protein content was significantly less (P < 0.05) in the Heat+HLU animals. These data demonstrate that heat stress before hindlimb unweighting can reduce the rate of disuse muscle atrophy. We postulate that HSP70 and/or other stress proteins play a role in the control of muscle atrophy induced by reduced contractile activity.

Regional hemodynamic responses to hypoxia and hypermetabolism in polycythemic dogs.

Normovolemic polycythemia did not improve the ability of either resting muscle or gut to maintain O2 uptake (VO2) during severe hypoxia because of the adverse effects of increased viscosity on blood flow to those regions. The present study tested whether increased metabolic demand would promote vasodilation sufficiently to overcome those effects. We measured whole body, muscle, and gut blood flow, O2 extraction, and VO2 in anesthetized dogs after increasing hematocrit to 65% and raising O2 demand with 2,4-dinitrophenol (n = 8). We also tested whether regional denervation (n = 8) and hypervolemia (n = 6) affected these responses. After raising hematocrit and metabolism, the dogs were ventilated with air, with 9% O2-91% N2, and again with air for 30-min periods. Reduced blood flow and increased O2 demand, caused by increased blood viscosity and 2,4-dinitrophenol, respectively, increased O2 extraction so that muscle VO2 was nearly supply limited in normoxia. Denervation showed that vasoconstriction had increased in gut and muscle with hypoxia onset but this was overcome after 15 min. By then, muscle was receiving a major portion of cardiac output, whereas gut showed little change. With hypervolemia cardiac output increased in hypoxia but neither gut nor muscle increased blood flow in those experiments. Because regional and whole body VO2 fell in all groups during hypoxia to the same extent found earlier in normocythemic dogs, any real benefit of polycythemia under the conditions of these experiments was dubious at best.

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.

Effects of aging and obesity on respiratory muscle phenotype in Zucker rats.

Because obesity results in an increased work of breathing, we tested the hypothesis that the oxidative properties and myosin heavy chain (MHC) isoform profiles in respiratory muscles would differ between lean and obese animals. Furthermore, we postulated that obesity-related changes in respiratory muscles would be independent of age. To test these hypothesis, samples of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles were removed from three age groups (young, adult, and old) of obese and lean Zucker rats. Citrate synthase (CS) activity was measured as a marker of oxidative capacity, and MHC isoforms were identified with gel electrophoresis. Analysis revealed that CS activity was significantly higher in the crural and costal diaphragms and parasternal intercostal of obese animals compared with lean animals (P < 0.05); this obesity-related increased in CS activity was related independent of age. Furthermore, respiratory muscle percent type IIb MHC was lower and percent type I MHC isoforms were higher in obese animals compared with lean animals. These data support the notion that obesity results in a fast-to-slow shift in MHC phenotype and an increase in oxidative capacity in major inspiratory muscles. The shift in MHC isoforms in obese animals is also age related, whereas the obesity-mediated increase in oxidative capacity is relatively independent of age.

Effects of vitamin E and alpha-lipoic acid on skeletal muscle contractile properties.

Initial experiments were conducted using an in situ rat tibialis anterior (TA) muscle preparation to assess the influence of dietary antioxidants on muscle contractile properties. Adult Sprague-Dawley rats were divided into two dietary groups: 1) control diet (Con) and 2) supplemented with vitamin E (VE) and alpha-lipoic acid (alpha-LA) (Antiox). Antiox rats were fed the Con rats' diet (AIN-93M) with an additional 10,000 IU VE/kg diet and 1.65 g/kg alpha-LA. After an 8-wk feeding period, no differences existed (P > 0.05) between the two dietary groups in maximum specific tension before or after a fatigue protocol or in force production during the fatigue protocol. However, in unfatigued muscle, maximal twitch tension and tetanic force production at stimulation frequencies < or = 40 Hz were less (P < 0.05) in Antiox animals compared with Con. To investigate which antioxidant was responsible for the depressed force production, a second experiment was conducted using an in vitro rat diaphragm preparation. Varying concentrations of VE and dihydrolipoic acid, the reduced form of alpha-LA, were added either individually or in combination to baths containing diaphragm muscle strips. The results from these experiments indicate that high levels of VE depress skeletal muscle force production at low stimulation frequencies.

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.

Economic evaluation of the fentanyl transdermal system for the treatment of chronic moderate to severe pain.

The fentanyl transdermal system (Duragesic) is an opioid analgesic indicated for the management of chronic moderate to severe pain. The purpose of this analysis is to estimate its economic value compared to two long-acting oral opioids. A cost-utility analysis was performed using a three-phased decision analytic model. The transdermal system had the highest expected cost during the first year of therapy ($2,491), moderately higher than the cost of a year of therapy with controlled-release morphine ($2,037) or controlled-release oxycodone ($2,307). The system also had the highest expected number of quality-adjusted life-days (QALDs) (244 compared to 236 for morphine and 231 for oxycodone), despite conservative assumptions. The fentanyl transdermal system achieved incremental cost-utility ratios of $20,709 (vs. morphine) and $5,273 (vs. oxycodone) per quality-adjusted life year (QALY) gained. In a conservative modeled analysis, the fentanyl transdermal system led to increased QALDs at a nominal increased cost. In the absence of head-to-head clinical trials, models help clarify cost and outcome trade-offs and provide a consistent theoretical framework for use by individual decisionmakers.

Tension development and duty cycle affect Qpeak and VO2peak in contracting muscle.

Ten canine gastrocnemius-plantaris muscle preparations were stimulated in situ to determine the interaction between tension development and the duty cycle in determining Qpeak and VO2peak. The muscle was stimulated with supramaximal voltage using four different stimulation protocols: 1) 5 twitches.s-1 (Tw), 2) 1 train.s-1-200 ms (1-200), 3) 1 train.s-1-300 ms (1-300), and 4) 2 trains.s-1-100 ms (2-100). Arterial and venous blood were sampled and Qpeak measured for determination of VO2peak. The total tension developed per second was integrated and averaged over 1 s (TDa) and used as an index of work of the muscle for each condition. The Qpeak and VO2peak were greater (P < 0.05) in the 1-200 condition compared to all other conditions. Further, Qpeak and VO2peak were greater (P < 0.05) in both the 1-300 and 2-100 conditions than during Tw: Qpeak (ml.kg-1.min-1) (mean +/- SE) for (Tw) = 928 +/- 65; (1-200) = 1368 +/- 102; (1-300) = 1150 +/- 96; (2-100) = 1189 +/- 89; VO2peak (ml.kg-1.min-1) for (Tw) = 108 +/- 8; (1-200) = 159 +/- 9; (1-300) = 135 +/- 11; (2-100) = 137 +/- 8. The TDa was significantly different among all conditions: TDa (N.kg-1) for (Tw) = 443 +/- 56; (1-200) = 606 +/- 81; (1-300) = 722 +/- 79; (2-100) = 522 +/- 41. We interpret these findings as an indication that the interaction of the duty cycle and tension development is a prime determinant of blood flow during muscle contractions.

Effects of intermittent ischemia on contractile properties and myosin isoforms of skeletal muscle.

PURPOSE: This study determined the effects of intermittent ischemia on the contractile properties, fatigue (Tf), and myosin heavy chain composition (MHC) in the rat gastrocnemius-plantarissoleus muscle (GPS) complex. METHODS: Fifty rats were divided into four groups: control (C, N = 12), severed (femoral artery) (S, N = 12), exercise (E, N = 13), and severed/exercise (SE, N = 13). Ischemia was elicited only in the SE group by daily exercise and the other groups served as controls. Exercise in the E and SE groups consisted of running on a treadmill approximately 35 min.d-1, 5 d.wk-1 for 7 wk. RESULTS: Body weight, muscle weight, and absolute force were less in the SE group compared with those in C (12, 18, and 12% respectively). However, relative force (N.g-1 of muscle) was greater in the SE group compared with that in C (8%). Maximal shortening velocity (Vmax) was lower in the SE group compared with that in all others (10-14%). Tf was less in the S group compared with that in C and E (28 and 30%, respectively). Type IIx MHC increased and type IIb decreased in gastrocnemius and plantaris muscles in SE compared with those in C. CONCLUSIONS: These data indicate that intermittent ischemia caused a decrease in muscle mass, maximal force development, and Vmax, but had no effect on Tf. The decrease in Vmax may have been related to myosin alterations in the muscles.

Effects of clenbuterol on contractile and biochemical properties of skeletal muscle.

We investigated the effects of clenbuterol on the muscle mass, contractile properties, myosin phenotype, and bioenergetic enzyme activity in the gastrocnemius (GS)-plantaris (PL)-soleus (SO) muscle complex. Rats were sham-injected or treated with clenbuterol (2 mg.kg-1, subcutaneously) for 14 d. Clenbuterol increased (P < 0.05) body weight and muscle complex weight. Also, clenbuterol treatment resulted in an increase in total muscle force production and maximal shortening velocity (P < 0.05). No difference (P > 0.05) in relative force production (force.g-1 muscle) existed between experimental groups. However, muscle fatigue increased with clenbuterol treatment. Myosin heavy chain (MHC) composition was not altered in the GS or PL muscles, but shifted toward the fast Type II MHC in the SO. Myosin light chain (MLC) composition was not altered in any of the muscles. Clenbuterol caused a decrease in oxidative and glycolytic enzyme activity in the GS and PL, but not the SO. These data suggest that the clenbuterol-induced increase in muscle mass and maximal force generation is due to hypertrophy of both fast and slow fibers. Furthermore, these findings support the notion that beta-agonists may be beneficial in combating conditions that result in muscle wasting and dysfunction.

Endurance training reduces the rate of diaphragm fatigue in vitro.

PURPOSE: The present study examined the effects of endurance training on the contractile and biochemical properties of the rat costal diaphragm in vitro. METHODS: Sixty-four rats were divided into two groups: exercise trained (T) and control (C). Training consisted of treadmill running 5 d x wk(-1), 60 min x d(-1) at approximately 70% of VO2max, over a 10-wk period. RESULTS: Control diaphragm strips produced an average of 12% less force from minute 15 to 50 of a 60-min in vitro fatigue protocol, compared with the T diaphragm strips (P < 0.01). T diaphragms had 10.1% higher citrate synthase (CS) and 12.1% higher superoxide dismutase (SOD) activities compared with the C (P < 0.05). Despite a significant decrease (P < 0.05) in Type IIb myosin heavy chains (MHC) and an increase (P < 0.05) in Type I MHC in T diaphragms, maximal shortening velocity (Vmax) in the diaphragm was not different between T and C animals. No differences were observed in specific force or the relative proportions of myosin light chains between groups. CONCLUSIONS: These findings suggest that endurance training reduces the rate of diaphragm fatigue in vitro but has no effect on Vmax or specific force.