A comparison of the electrophysiological effects of two organophosphates, mipafox and ecothiopate, on mouse limb muscles

Adult male albino mice were given single subcutaneous injections of either mipafox (110 mumol/kg) or ecothiopate (0.5 mumol/kg), two organophosphorus compounds (OPs). Acetylcholinesterase activity was measured in the soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles. At 7 and 28 days after dosing, in vitro electrophysiological measurements were carried out in the soleus and EDL. Action potentials and end-plate potentials were evoked at 30 Hz and recorded intracellularly from single muscle fibers. The amplitudes, time course, and latencies of these potentials were measured and the variability (jitter) of latencies was calculated. Recordings after mipafox were also made with 3-Hz stimulation. Acetylcholinesterase activity was inhibited by mipafox (65% in the soleus; 76% in the EDL) and ecothiopate (59% in the soleus; 42% in the EDL). Mipafox and ecothiopate both increased postjunctional (muscle action potential) jitter in the soleus and EDL at 7 days after dosing. Organophosphates caused an increase in end-plate potential amplitudes in the soleus. Mipafox caused an increase in prejunctional (end-plate potential) jitter at 28 days after dosing in both muscles. A single dose of ecothiopate also caused an increase in prejunctional jitter at 28 days in the soleus. The OP-induced increase in jitter was different at different frequencies of stimulation. The results show that there are electrophysiological changes in both muscles after administration of organophosphorus compounds. The slow-twitch soleus appears more sensitive to prejunctional changes caused by OPs than the fast-twitch EDL.     

Muscle creatine kinase-deficient mice. II. Cardiac and skeletal muscles exhibit tissue-specific adaptation of the mitochondrial function

Functional properties of in situ mitochondria and of mitochondrial creatine kinase were studied in saponin-skinned fibers taken from normal and M-creatine kinase-deficient mice. In control animals, apparent Km values of mitochondrial respiration for ADP in cardiac (ventricular) and slow-twitch (soleus) muscles (137 +/- 16 microM and 209 +/- 10 microM, respectively) were manyfold higher than that in fast-twitch (gastrocnemius) muscle (7.5 +/- 0.5 microM). Creatine substantially decreased the Km values only in cardiac and slow-twitch muscles (73 +/- 11 microM and 131 +/- 21 microM, respectively). As compared to control, in situ mitochondria in transgenic ventricular and slow-twitch muscles showed two times lower Km values for ADP, and the presence of creatine only slightly decreased the Km values. In mutant fast-twitch muscle, a decrease rather than increase in mitochondrial sensitivity to ADP occurred, but creatine still had no effect. Furthermore, in these muscles, relatively low oxidative capacity was considerably elevated. It is suggested that in the mutant mice, impairment of energy transport function in ventricular and slow-twitch muscles is compensated by a facilitation of adenine nucleotide transportation between mitochondria and cellular ATPases; in fast-twitch muscle, mainly energy buffering function is depressed, and that is overcome by an increase in energy-producing potential.     

Molecular forms of acetylcholinesterase in dystrophic (mdx) mouse tissues

We analyzed the activity of acetylcholinesterase (AChE) and its molecular forms in the tissues of normal and dystrophic (mdx) mice, at different developmental stages. We studied the brain, the heart and the serum, in addition to four predominantly fast-twitch muscles (tibialis, plantaris, gastrocnemius and extensor digitorum longus (EDL)) and the slow-twitch, soleus muscle. We found no difference between mdx and control mice in the AChE activity of the brain and the heart. The skeletal muscles affected by the disease undergo active degeneration counterbalanced by regeneration between 3 and 14 weeks after birth. The distribution of AChE patches associated with neuromuscular junctions was abnormally scattered in mdx muscles, and in some cases (tibialis and soleus), the number of endplates was more than twice that of normal muscles. There were only minor differences in the concentration and pattern of AChE molecular forms during the acute phase of muscle degeneration and regeneration. After this period, however, we observed a marked deficit in the membrane-bound G4 molecular form of AChE in adult mdx tibialis, gastrocnemius and EDL but not in the plantaris or in the soleus, as compared with their normal counterparts. Whereas the amount of AChE markedly decreased in the serum of normal mice during the first weeks of life, it remained essentially unchanged in the serum of mdx mice. It is likely that this excess of AChE activity in serum originates from the muscles. A deficit in muscle G4 was also reported in other forms of muscular dystrophy in the mouse and chicken. Since it is not correlated to the acute phase of the disease in mdx and also occurs in genetically different dystrophies, it probably represents a secondary effect of the dystrophy.     

Interorgan signaling between adipose tissue metabolism and skeletal muscle uncoupling protein homologs: is there a role for circulating free fatty acids?

Uncoupling proteins 3 and 2 (UCP3 and UCP2) are two newly cloned genes that have been implicated in the regulation of lipids as fuel substrate in skeletal muscle on the basis that their mRNA expressions are upregulated during starvation (when fat stores are being rapidly mobilized) and downregulated during the early phase of refeeding (when fat stores are being rapidly replenished). To test the hypothesis that circulating free fatty acids (FFAs) may have a physiological role as an interorgan signal linking these dynamic changes in the fat stores to skeletal muscle expression of UCP3 and UCP2, the mRNA levels of these UCP homologs were examined in fed and fasted rats treated with the antilipolytic agent nicotinic acid. In 46-h fasted rats, we observed a threefold increase in serum FFA levels and increases in UCP3 and UCP2 mRNA levels that were more marked in the gastrocnemius and tibialis anterior muscles (predominantly fast-twitch fibers) than in the soleus muscle (predominantly slow-twitch fibers). Treatment with nicotinic acid blunted the fasting-induced increase in serum FFA levels and prevented the increase in mRNA levels of UCP3 and UCP2 in the soleus muscle, but had little or no effect on the elevated mRNA levels of these UCP homologs in the gastrocnemius and tibialis anterior muscles. Furthermore, treatment of ad libitum-fed animals with nicotinic acid resulted in a twofold reduction in serum FFA levels (i.e., by a magnitude similar to that observed during early refeeding) and significant reductions in UCP3 and UCP2 mRNA levels in the soleus muscle, but not in the gastrocnemius or tibialis anterior muscles. These results revealed a muscle-type dependency in the way UCP2 and UCP3 gene expression in skeletal muscle is regulated, and suggest that the hypothesis that circulating FFAs function as an interorgan signal between fat stores and skeletal muscle UCP3 and UCP2 gene expression is adequate only for slow-twitch (oxidative) muscles. Consequently, a signal(s) other than circulating FFAs must be implicated in the link between dynamic changes in body fat stores and UCP expression in predominantly fast-twitch (glycolytic/oxidative-glycolytic) muscles, which constitute the major fiber type of the total skeletal muscle mass and which have high susceptibility to developing insulin resistance and impairment in substrate utilization in metabolic diseases.     

Na(+)-K+ ATPase concentration in different adult rat skeletal muscles is related to oxidative potential

To investigate the relationship among fibre type, oxidative potential, and Na(+)-K+ ATPase concentration in skeletal muscle, adult male Wistar rats weighing 259 +/- 8 g (mean +/- SE) were sacrificed and the soleus (SOL), extensor digitorum longus (EDL), red vastus lateralis (RV), and white vastus lateralis (WV) removed. These muscles were chosen as being representative of the two major fibre type populations: slow twitch (SOL) and fast twitch (EDL, RV, WV) and exhibiting either a high (SOL, EDL, RV) or low (WV) oxidative potential. Na(+)-K+ ATPase concentration (pmol.g-1 wet weight), measured by the [3H]ouabain binding technique, differed (p < 0.01) only between the WV (238 +/- 7.9) and the SOL (359 +/- 9.6), EDL (365 +/- 10), and RV (403 +/- 12). Similarly, muscle oxidative potential as measured by the maximal activity of citrate synthase was different (p < 0.01) only between the WV and the other three muscles. Citrate synthase activity (mumol.min-1.g-1 wet weight) was 4.0 +/- 0.7, 12.3 +/- 0.9, 9.1 +/- 0.7, and 11.3 +/- 1.0 in the WV, SOL, EDL, and RV, respectively. These results indicate that Na(+)-K+ ATPase concentration is not related to the speed of contraction but to the oxidative potential of the muscle. Since chronic activity is a primary determinant of oxidative potential, it would be expected that increases in Na(+)-K+ ATPase would accompany increases in muscle utilization.     

Effects of an anabolic steroid and sprint training on selected histochemical and morphological observations in rat skeletal muscle types

The effects on selected histochemical and morphological parameters of anabolic steroid administration and of high-intensity sprint running, separately, and in combination, were studied in young adult male rats. Dianabol (methandrostenolone) 1 mg/day for 8 weeks had no significant effects on phosphorylase or glycogen staining intensities and on fiber area in skeletal muscles of either trained or sedentary animals. The program of sprint training resulted in significantly decreased intensities of phosphorylase in all ten regions of the gastrocnemius, plantaris, and soleus muscles that were studied. Glycogen localization was significantly increased with training in five regions of the gastrocnemius and plantaris muscles which contained predominantly fast-switch fibers. No changes in fiber area occurred with the training program. We conclude from these results that (a) normal androgen levels in young, healthy male animals are sufficiently high so that the intake of large doses of anabolic steroid does not result in the stimulation of glycogen metabolism or hypertrophy of skeletal muscle; (b) the changes induced by high-intensity, short-duration sprint training suggest that the existing glycolytic capacity of muscle is adequate to supply the muscles energy needs even during the stress of very strenous exercise, and that more fast-twitch fibers were recruited by the exercise regimen than slow-twitch fibers.     

Paravertebral muscles in experimental scoliosis: a light and electron microscopic study

Experimental structural dextroconvex scoliosis was produced in rabbits by costotransversolisis with transversectomy and releasing of paravertebral muscles between TVII and TX on the right side. Two compensatory curves developed on the upper dorsal and lumbar levels. Biopsies of paravertebral muscles in experimental animals included, besides areas of normal tissue, a considerable derangement of the cell contractile apparatus with sarcoplasmic dilation and eventual cell disintegration and necrosis. Histological changes varied along levels, the convexity being more affected. The severity of changes and reduction in body weight and length were correlated with the degree of scoliosis. A selective atrophy of slow-twitch fibers was observed in experimental animals, especially at the level of the main curve, whereas fast-twitch fiber atrophy was more important caudally. Control animal biopsies always appeared normal. Our experimental model shows an overt participation of paravertebral muscles in the establishment of compensatory processes following scoliosis, although the role that paravertebral muscles play in the etiopathogenesis of human idiopathic scoliosis requires further investigation.     

Ion transport and membrane potential in CNS myelinated axons. II. Effects of metabolic inhibition

Compound resting membrane potential was recorded by the grease gap technique (37 degrees C) during glycolytic inhibition and chemical anoxia in myelinated axons of rat optic nerve. The average potential recorded under control conditions (no inhibitors) was -47 +/- 3 (SD) mV and was stable for 2-3 h. Zero glucose (replacement with sucrose) depolarized the nerve in a monotonic fashion to 55 +/- 10% of control after 60 min. In contrast, glycolytic inhibition with deoxyglucose (10 mM, glucose omitted) or iodoacetate (1 mM) evoked a characteristic voltage trajectory consisting of four distinct phases. A distinct early hyperpolarizing response (phase 1) was followed by a rapid depolarization (phase 2). Phase 2 was interrupted by a second late hyperpolarizing response (phase 3), which led to an abrupt reduction in the rate of potential change, causing nerves to then depolarize gradually (phase 4) to 75 +/- 9% and 55 +/- 6% of control after 60 min, in deoxyglucose and iodoacetate, respectively. Pyruvate (10 mM) completely prevented iodoacetate-induced depolarization. Effects of glycolytic inhibitors were delayed by 20-30 min, possibly due to continued, temporary oxidative phosphorylation using alternate substrates through the tricarboxylic acid cycle. Chemical anoxia (CN- 2 mM) immediately depolarized nerves, and phase 1 was never observed. However a small inflection in the voltage trajectory was typical after approximately 10 min. This was followed by a slow depolarization to 34 +/- 4% of control resting potential after 60 min of CN-. Addition of ouabain (1 mM) to CN--treated nerves caused an additional depolarization, indicating a minor glycolytic contribution to the Na+-K+-ATPase, which is fueled preferentially by ATP derived from oxidative phosphorylation. Phases 1 and 3 during iodoacetate exposure were diminished under nominally zero Ca2+ conditions and abolished with the addition of the Ca2+ chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA; 5 mM). Tetraethylammonium chloride (20 mM) also reduced phase 1 and eliminated phase 3. The inflection observed with CN- was eliminated during exposure to zero-Ca2+/EGTA. A Ca2+-activated K+ conductance may be responsible for the observed hyperpolarizing inflections. Block of Na+ channels with tetrodotoxin (TTX; 1 microM) or replacement of Na+ with the impermeant cation choline significantly reduced depolarization during glycolytic inhibition with iodoacetate or chemical anoxia. The potential-sparing effects of TTX were less than those of choline-substituted perfusate, suggesting additional, TTX-insensitive Na+ influx pathways in metabolically compromised axons. The local anesthetics, procaine (1 mM) and QX-314 (300 microM), had similar effects to TTX. Taken together, the rate and extent of depolarization of metabolically compromised axons is dependent on external Na+. The Ca2+-dependent hyperpolarizing phases and reduction in rate of depolarization at later times may reflect intrinsic mechanisms designed to limit axonal injury during anoxia/ischemia.     

Muscle unloading induces slow to fast transitions in myofibrillar but not mitochondrial properties. Relevance to skeletal muscle abnormalities in heart failure

Muscle deconditioning is a common observation in patients with congestive heart failure (CHF), chronic obstructive pulmonary disease, neuromuscular diseases or prolonged bed rest. To gain further insight into metabolic and mechanical properties of deconditioned slow-twitch (soleus) or fast-twitch (EDL) skeletal muscles, we induced experimental muscle deconditioning by hindlimb suspension (HS) in rats for 3 weeks. Cardiac muscle was also studied. Besides profound muscle atrophy, increased proportion of fast type II fibers as well as fast myosin isoenzymes, we found decreased calcium sensitivity of Triton X-100 skinned fiber bundles of soleus muscle directed towards the fast muscle phenotype. Glycolytic enzymes such as hexokinase and pyruvate kinase were increased, and the LDH isoenzyme pattern was clearly shifted from an oxidative to an anaerobic profile. Creatine kinase (CK) and myokinase activities were increased in HS soleus towards EDL values. Moreover, the M-CK mRNA level was greatly increased in soleus, with no change in EDL. However, oxygen consumption rate assessed in situ in saponin skinned fibers (12.5 +/- 0.8 in C and 15.1 +/- 0.9 micromol O2/min/g dw in HS soleus compared to 7.3 +/- 1.3 micromol O2/min/g dw in control EDL), as well as mitochondrial CK (mi-CK) and citrate synthase activities, were preserved in HS soleus. Following deconditioning no change in Km for ADP of mitochondrial respiration, either in the absence (511 +/- 92 in C and 511 +/- 111 microM in HS soleus compared to 9 +/- 4 microM in control EDL) or presence of creatine (88 +/- 10 in C and 95 +/- 16 microM in HS soleus compared to 32 +/- 9 microM in control EDL), was found. The results show that muscle deconditioning induces a biochemical and functional slow to fast phenotype transition in myofibrillar and cytosolic compartments of postural muscle, but not in the mitochondrial compartment, suggesting that these compartments are differently regulated under conditions of decreased activity.     

The effect of bipolar electrocautery on peripheral nerves

Although bipolar cautery was designed to minimize trauma to the central nervous system, little is known about the effects of bipolar cautery on peripheral nerve tissue. This experiment was designed to study the effect of direct bipolar cautery on a peripheral nerve and the muscles innervated by that nerve. Lewis rats (n = 200) were assigned to five different groups: control, sham, and three cautery groups (duration of either 0.5, 1.0, or 1.5 seconds). The hind limb tibial nerves were isolated in the sham group and isolated and cauterized in the cautery groups. Assessments performed at 2 hours, 2 weeks, 4 weeks, and 8 weeks postoperatively included isometric contractile function studies of both a fast- and a slow-twitch muscle, muscle weights, and nerve histology/morphometry. Significant muscle weight loss and reduced muscle function were found in the cautery groups at 2, 4, and 8 weeks (p < 0.05). Histologically, the nerves of the cautery groups showed nerve damage consistent with Sunderland's type 4 nerve injury when examined at 2 weeks and showed nerve regeneration at 4 and 8 weeks. Both the fast-twitch muscle and the shorter duration cautery were associated with faster recovery relative to the slow-twitch muscles and longer duration cautery, respectively. Bipolar cautery, as administered to rat tibial nerves in this experiment, is associated with a significant injury to the nerve and loss of function of the muscles innervated by the nerve.     

Cytomegalovirus DNA can be detected in peripheral blood mononuclear cells from all seropositive and most seronegative healthy blood donors over time

1. The purpose of this study was to assess the potential of various preservation solutions, orginally designed for solid organs, to protect muscle function during cold storage. 2. The soleus (SOL) and the cutaneous trunci (CT) muscle from the rat were isolated and stored for 2, 4 or 8 h at 10 degrees C. The solutions used, listed in order from an intracellular to an extracellular-like composition, were: University of Wisconsin (UW), Euro-Collins (EC), HTK-Bretschneider (HTK), reversed St. Thomas' Hospital (ST2) and Krebs-Henseleit (KH). After cold storage, the muscles were tested by direct electrical stimulation to obtain the maximum twitch tension (Pt) and the maximum tetanus tension (P0). Subsequently, the muscles were prepared for morphological analysis. 3. In general, storage at 10 degrees C caused a gradual decrease of Pt and P0 with time. After 8 h of storage in the extracellular-like solutions KH and ST2, the P0 was about 50% (SOL) and 35% (CT) of control. Eight hours of storage in intracellular-like solutions resulted in a P0 of 50% of control for HTK, in a P0 of 40% (SOL) and 67% (CT) for UW, but in a P0 of 5% (SOL) and 26% (CT) for EC. These findings corresponded well with the morphological observations. 4. It is concluded that the effects of 10 degrees C storage on skeletal muscle function are not predominantly determined by the intra- or extracellular-like composition of the solutions used. Both UW and HTK were most effective (P0 > 50% of control) in preserving muscle function.     

Murine endodermal F9E cells, derived from the teratocarcinoma line F9, contain high basal levels of retinoic acid receptors (RARs and RXRs) but are not sensitive to the actions of retinoic acid

We observed differences in the capillary architecture of the skeletal muscles that have different fiber metabolism. The soleus, the vastus intermedius and the tibialis anterior muscles of adult Wistar rats were prepared using two different techniques. Samples for adenosine triphosphatase (ATPase) staining were prepared following Dubovitz's method, and the distributions of fiber type, Types 1, 2A and 2B, were analyzed. Then, corrosion casts of capillary architecture of these muscles prepared following Murakami's method were observed with a scanning electron microscope (SEM) and compared with the fiber distribution. The fiber type composition of the soleus muscle showed Type 1 (slow-twitch) dominance and that of the vastus intermedius and the tibialis anterior muscle showed Type 2 (fast-twitch) dominance. The capillaries of the soleus muscle were tortuous, and this was thought to be advantageous for blood supply. In contrast, the capillaries of the vastus intermedius and tibialis anterior muscles had a relatively parallel pattern. Additionally, two different patterns of capillary architecture that appeared to correspond to certain metabolic characteristic of different muscle fiber types were preserved with corrosion casting. In conclusion, comparative studies on capillary architecture of the skeletal muscles are useful for analyses of its function.     

Direct administration and utilization of [1-13C]glucose by fetal brain and liver tissues under normal and ischemic conditions: 1H, 31P, and 13C NMR studies

The acute and delayed effects of anoxia on synaptic transmission and long-term potentiation (LTP) were examined in the CA1 region of rat hippocampal slices. Oxygen deprivation for 20 minutes completely but reversibly depressed excitatory postsynaptic potentials mediated by both N-methyl-D-aspartate receptors (NMDAR) and non-NMDAR. Although LTP was reliably produced by a single tetanus delivered 30 minutes after reoxygenation, LTP could not be induced when a tetanus was delivered 70 to 100 minutes after reoxygenation. A tetanus delivered 100 minutes after reoxygenation produced lasting synaptic enhancement when 100 mumol/L D,L-amino-phosphonovaleric acid (APV), a competitive NMDAR antagonist, was administered during the period of oxygen deprivation. The delayed effects of oxygen deprivation were not blocked when APV was administered after oxygen deprivation. Similarly, the delayed effects on LTP induction were overcome by inhibitors of nitric oxide synthase when the nitric oxide synthase inhibitors were administered during anoxia, but not when administered after oxygen deprivation. These results suggest that untimely activation of NMDAR and nitric oxide release during anoxia produce delayed inhibition of LTP induction and may be involved in the memory defects that occur subsequent to cerebral hypoxia.     

Oxidation of acetate and octanoate and its relation to glucose metabolism in contracting porcine carotid artery

The oxidation of octanoate and acetate was measured in segments of porcine carotid arteries to ascertain whether the oxidation of exogenous fatty acid substrates (acetate and octanoate) is augmented during contraction induced by K(+)-depolarization. The oxidation of acetate increased from 7 +/- 1 to 14 +/- 2 nmol/min/g (P < 0.01) during sustained isometric contraction. Octanoate oxidation increased from 11 +/- 1 to 14 +/- 1 nmol/min/g (P < 0.05). The rate of oxidation of neither acetate nor octanoate was affected by the presence or absence of glucose either in resting or contracting arteries Acetate or octanoate oxidation could account for the majority of O2 consumption during contraction. Octanoate but not acetate inhibited glucose uptake and glycolysis in resting muscles. In contrast to augmented acetate and octanoate metabolism during contraction, there was a "down-regulation" of glucose metabolism in contracting muscles as evidenced by a decrease in the rate of glucose uptake, glycolysis and lactic acid production during sustained isometric contraction. Thus, contractile activation of vascular smooth muscle is associated with a shifting pattern of substrate utilization. Exogenous acetate or octanoate can serve as the primary oxidative substrate during sustained isometric contraction.     

Resistance to anoxic injury in the dorsal columns of adult rat spinal cord following demyelination

In order to examine the relationship between myelination and sensitivity to anoxia in adult white matter, we studied action potential conduction in the spinal cord dorsal column of adult rats in which focal demyelinating lesions had been produced using ethidium bromide/X-irradiation. Acutely isolated spinal cords from control rats and following demyelination were maintained in vitro at 36 degrees C and compound action potentials were studied following supramaximal stimulation. The compound action potential was totally abolished within 12 min of the onset of anoxia in normal dorsal columns, but was not abolished until 50 min following the onset of anoxia in demyelinated dorsal columns. Compound action potentials showed significantly greater recovery (to 58.1 +/- 12.2% of control amplitude) in demyelinated dorsal columns compared to controls (30.8 +/- 5.3%) following 120 min of reoxygenation. These results show that focal demyelination is associated with reduced sensitivity to anoxia within white matter of the adult spinal cord.     

The effect of ischemic preconditioning on the recovery of skeletal muscle following tourniquet ischemia

It has been well documented that ischemic preconditioning limits ischemic-reperfusion injury in cardiac muscle, but the ability of ischemic preconditioning to limit skeletal muscle injury is less clear. Previous reports have emphasized the beneficial effects of ischemic preconditioning on skeletal muscle structure and capillary perfusion but have not evaluated muscle function. We investigated the morphologic and functional consequences of ischemic preconditioning, followed by a 2-hour period of tourniquet ischemia on muscles in the rat hindlimb. The 2-hour ischemia was imposed without preconditioning, or was preceded by three brief (10 minutes on/10 minutes off) preischemic conditioning intervals. We compared muscle morphology, isometric contractile function, and muscle fatigue properties in predominantly fast-twitch, tibialis anterior muscles 3 (n = 8) and 7 (n = 8) days after ischemia-reperfusion. Two hours of ischemia, followed by reperfusion, results in a 20 percent reduction of muscle mass (p < 0.05) and a 33 percent reduction in tetanic tension (p < 0.05) when compared with controls (n = 8) at 3 days. The same protocol, when preceded by ischemic preconditioning, results in similar decreases in muscle mass and contractile function. Neuromuscular transmission was also impaired in both ischemic groups 7 days after ischemia. Nerve-evoked maximum tetanic tension was 69 percent of the tension produced by direct muscle stimulation in the ischemia group and 65 percent of direct tension in the ischemic preconditioning/ischemia group. In summary, ischemic preconditioning, using the same protocol reported to be effective in limiting infarct size in porcine muscle, had no significant benefit in limiting injury or improving recovery in the ischemic rat tibialis anterior. The value of ischemic preconditioning in reducing imposed ischemic-reperfusion-induced functional deficits in skeletal muscle remains to be demonstrated.     

Contribution of phosphocreatine and aerobic metabolism to energy supply during repeated sprint exercise

This study examined the contribution of phosphocreatine (PCr) and aerobic metabolism during repeated bouts of sprint exercise. Eight male subjects performed two cycle ergometer sprints separated by 4 min of recovery during two separate main trials. Sprint 1 lasted 30 s during both main trials, whereas sprint 2 lasted either 10 or 30 s. Muscle biopsies were obtained at rest, immediately after the first 30-s sprint, after 3.8 min of recovery, and after the second 10- and 30-s sprints. At the end of sprint 1, PCr was 16.9 +/- 1.4% of the resting value, and muscle pH dropped to 6.69 +/- 0.02. After 3.8 min of recovery, muscle pH remained unchanged (6.80 +/- 0.03), but PCr was resynthesized to 78.7 +/- 3.3% of the resting value. PCr during sprint 2 was almost completely utilized in the first 10 s and remained unchanged thereafter. High correlations were found between the percentage of PCr resynthesis and the percentage recovery of power output and pedaling speed during the initial 10 s of sprint 2 (r = 0.84, P < 0.05 and r = 0.91, P < 0.01). The anaerobic ATP turnover, as calculated from changes in ATP, PCr, and lactate, was 235 +/- 9 mmol/kg dry muscle during the first sprint but was decreased to 139 +/- 7 mmol/kg dry muscle during the second 30-s sprint, mainly as a result of a approximately 45% decrease in glycolysis. Despite this approximately 41% reduction in anaerobic energy, the total work done during the second 30-s sprint was reduced by only approximately 18%. This mismatch between anaerobic energy release and power output during sprint 2 was partly compensated for by an increased contribution of aerobic metabolism, as calculated from the increase in oxygen uptake during sprint 2 (2.68 +/- 0.10 vs. 3.17 +/- 0.13 l/min; sprint 1 vs. sprint 2; P < 0.01). These data suggest that aerobic metabolism provides a significant part (approximately 49%) of the energy during the second sprint, whereas PCr availability is important for high power output during the initial 10 s.     

Effects of adrenalectomy or RU-486 on rat muscle fibers during hindlimb suspension

The purpose of this study was to investigate the effects of a glucocorticoid antagonist, RU-486, and of adrenalectomy (ADX) on rat skeletal muscle structural properties after 3, 7, and 14 days of hindlimb suspension (H). After H, a significant loss in muscle weight was observed as early as 3 days in soleus (SOL; -10%) and adductor longus (AL; -14%) muscles. In SOL, after only 7 days, a reduction (-14%) in type I fiber percent distribution occurred, accompanied by an increase (+129%) in intermediate type I fibers. Fiber type changes increased depending on the duration of H. In AL muscle, no change occurred after H in the fiber type composition despite a similar degree of muscle atrophy. Treatment with RU-486 or ADX significantly reduced the loss of SOL weight observed after 14 days (-42 and -44%, respectively, vs. -50% for H rats), delayed the SOL atrophy (from 3 to 7 days), and normalized the shift in fiber type distribution induced by H. In SOL, administration of RU-486 (but not ADX) partly prevented the reduction in size induced by H of all the fibers. In AL, neither treatment affected the extent of muscle atrophy, even though the reduction in type IIa fiber size was prevented by RU-486 but not by ADX after 14 days of suspension. ADX or RU-486 administration did not prevent the extensor digitorum longus weight loss observed after 14 days of suspension but allowed a recovery of its normal fiber type composition.(ABSTRACT TRUNCATED AT 250 WORDS)