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J K Barclay

Publications and source records attributed to J K Barclay.

At least 19 recordsLinked to original sources
PubMed2001

A1 receptor activation decreases fatigue in mammalian slow-twitch skeletal muscle in vitro.

To test the hypothesis that adenosine improves skeletal muscle cell function, we exposed curarized mouse soleus and extensor digitorum longus (EDL) to a range of concentrations of adenosine (10(-9) M to 10(-5) M). Muscles contracted in Krebs-Henseleit bicarbonate buffer (27 degrees C, 95% O2 and 5% CO2) for 500 ms at 50 Hz once every 90 s. Soleus fatigued significantly less with adenosine present at concentrations of 10(-8) M and higher than with the Krebs-Henseleit vehicle control. Adenosine significantly improved force generation or delayed fatigue of EDL only with the initial adenosine challenge. To investigate the receptor population involved, we exposed soleus to agonists specific for A1 receptors (N6-cyclopentyladenosine, CPA), or A2 receptors (CGS 21680 hydrochloride, CGS), or A3 receptors (N6-benzyl-5'-N-ethylcarboxamidoadenosine, BNECA). CPA (A1) significantly decreased fatigue compared with the Krebs-Henseleit vehicle control at concentrations of 10(-9) M and higher. Muscles exposed to the A2 and A3 agonists did not differ from a Krebs-Henseleit plus methanol control. Phenylephrine (10(-6) M), an alpha-adrenergic agonist that increases the concentration of inositol triphosphate (IP3), significantly improved developed force in soleus. Neither a permeable cAMP analog, 8-bromo-cAMP (10(-5) M), nor a beta, agonist, isoproterenol (10(-6) M), had an effect on force generation in the soleus when compared with a saline control. Thus adenosine slowed fatigue in slow-twitch skeletal muscle through A1 receptors.

Adenosine↗
PubMed2001

Contractile function in vitro of slow-twitch skeletal muscle from weanling mice subjected to wasting malnutrition.

Our hypothesis was that malnutrition sufficient to produce weight loss in weanling mice would decrease the ability of slow-twitch skeletal muscle to develop and maintain force. We isolated muscles from 3 groups (n = 5) of weanling C57BL/6J mice of both sexes (i) mice at 19 days of age serving as zero-time or baseline controls (CONT) (ii) mice fed for the next 14 days with a low-protein diet that produces features of incipient kwashiorkor (LPD) and (iii) mice fed for the next 14 days with a complete diet (NORM). Muscles were also obtained from 5 adult mice 7-9 months of age (MAT). We stimulated the soleus at 50 Hz for 500 ms at 0.6 tetanic contractions per min (tet x min(-1)), 6 tet x min(-1), and 30 tet x min(-1) in Krebs-Henseleit bicarbonate buffer at 27 degrees C gassed with 95% O2 and 5% CO2. The initial developed force (mN x mm(-2)) at 0.6 tet x min(-1) did not differ across groups (CONT 211.7 +/- 16.0, LPD 274.2 +/- 41.6, NORM 246.8 +/- 38.0, MAT 210.8 +/- 10.6). The fatigue rate (mN x mm(-2) x min(-1)) at 6 tet x min(-1) was significantly slower in muscles from CONT (0.6 +/- 0.3) and LPD (0.6 +/- 0.4) than in NORM (2.4 +/- 0.6) and MAT (2.3 +/- 0.2). At 30 tet x min(-1), the fatigue rate (mN x mm(-2) x min(-1)) did not differ across groups (CONT 2.4 +/- 0.5, LPD 2.7 +/- 0.5, NORM 2.5 +/- 0.4, MAT 2.0 +/- 0.2). After stimulation at 6 tet x min(-1) and 30 tet x min(-1), only muscles from CONT and LPD recovered to 100%. Because muscles from LPD mice developed equal force, fatigued less, and recovered from fatigue to a greater extent than muscles from NORM mice, we rejected the hypothesis. The function of the tissue remaining in the muscles from LPD mice approximated that of muscles from mice at 19 days of age rather than muscles from either mice of the same age fed a complete diet or adult mice.

Animals↗
PubMed1999

Polycythemia decreases fatigue in tetanic contractions of canine skeletal muscle.

PURPOSE: The effects of an acute polycythemia on muscle fatigue development were investigated in the self-perfused canine gastrocnemius in situ. METHODS: Following isolation of the gastrocnemius, dogs (N = 5) were made polycythemic through a bolus injection of packed erythrocytes (hematocrit (Hct) = 90-92%) to raise systemic Hct to 63.5 +/- 0.5%. Subsequently, the gastrocnemius was stimulated, through the sciatic nerve, to perform 20 min of isotonic tetanic contractions (60 x min(-1), 200 ms, 50Hz). Control (normocythemic) animals (N = 5) underwent an identical contraction regimen. RESULTS: Although blood flow to the gastrocnemius was not different at any time, oxygen delivery was significantly increased during polycythemia (peak = 33.7 +/- 2.2 mL x 100 g(-1) x min-1) over control (peak = 25.1 +/- 2.1 mL x 100 g(-1)x min(-1)) at all times during contraction. Oxygen uptake by the gastrocnemius, although consistently increased, was not significantly different between the normocythemic and polycythemic conditions at any time. The rate of fatigue was significantly decreased over the first 6 min of contraction in polycythemic animals (3.5 +/- 0.6% x min(-1)) when compared with controls (5.8 +/- 0.7% x min(-1)). Subsequent fatigue development was not different between groups. As a result of the early rate differences in fatigue, however, the work production in polycythemic animals was significantly greater than in normocythemic dogs for the duration of the contraction period. CONCLUSION: We conclude that during high metabolic rate isotonic tetanic contractions, muscle fatigue development is diminished by polycythemia, but the ergogenic effect appears to be transient.

Analysis of Variance↗
PubMed1998

Microvascular hematocrit and permeability-surface area product in contracting canine skeletal muscle in situ.

The dynamics of the microvasculature of the blood-perfused canine gastrocnemius-plantaris muscle in situ at rest and during contraction were determined using multiple-indicator dilution analysis. Permeability-surface area product (PS) was estimated using a bolus indicator dilution of 86Rb, with 125I-albumin serving as the reference tracer, while microvascular hematocrit (Hmv) was estimated using the relationship between plasma (125I-albumin) and erythrocyte (51Cr) tracer washout curves. The muscle was stimulated to contract, under self-perfusion, for 3-min periods with either isometric twitch (1.5, 3, or 5 Hz; 4 ms) or tetanic (20, 40, or 60 trains/min, 200 ms, 100 Hz) contractions, separated by 25 min of rest, randomized to prevent ordering effects. At all stimulation frequencies, Hmv increased significantly from rest value of 36.5 +/- 1.6% to 3 min of either isometric twitch or tetanic contractions. PS rose significantly from 0.08 +/- 0.002 ml/g min at rest to a maximum of 0. 40 +/- 0.01 ml/g min at 60 isometric tetanic contractions per minute and 0.38 +/- 0.01 at 5 Hz. Changes in PS appeared related to stimulation frequency in both twitch and tetanic contractions. The change in Hmv with muscle contraction appeared to depend on contraction frequency during twitch contractions only, but was independent of stimulus frequency during tetanic contractions.

Animals↗
PubMed1998

Extravascular adenosine influences endothelium-derived nitric oxide release from perfused dog semitendinosus artery.

We tested the hypothesis that extravascular adenosine induces the release of vasodilatory products from endothelial cells lining skeletal muscle vessels. Endothelium-intact (n = 35) and -denuded (n = 5) dog semitendinosus intramuscular arteries were isolated, cannulated, and placed in 100-mL baths containing Krebs-Henseleit bicarbonate buffer (Krebs) at 37 degrees C and gassed with 95% O2--5% CO2. Each vessel, as well as a parallel tubing segment (avascular control), was perfused at 3.5 +/- 0.2 mL/min (inflow pressure 94 +/- 2 mmHg; 1 mmHg = 133.3 Pa) with Krebs containing 100 microM phenylephrine, 6% dextran, and 15 units/mL superoxide dismutase. Perfusate from all segments dripped onto endothelium-denuded dog femoral artery rings. The addition of 10 microM acetylcholine to the perfusate to test the functional integrity of endothelium-intact donor segments did not alter resistance in vessel segments or change force in rings. The addition of 100 microM adenosine to the extravascular bath decreased resistance 1.5 +/- 0.4 mmHg.mL-1.min-1 in vessel segments but was without effect on downstream rings. When acetylcholine was retested in the presence of extravascular adenosine, a relaxation (16 +/- 6%) occurred in rings receiving perfusate from endothelium-intact segments but not endothelium-denuded or tubing segments. This relaxation was eliminated by N omega-nitro-L-arginine (10 microM), a nitric oxide synthase inhibitor, and was attenuated to 4 +/- 1% by 8-phenyltheophylline (10 microM), an adenosine receptor antagonist. Thus adenosine, in conjunction with acetylcholine, acting through a receptor-mediated event, resulted in the release of nitric oxide from the endothelium of perfused intramuscular arteries, indicating the potential for extravascular conditions to influence the release of endothelium-derived products.

Acetylcholine↗
PubMed1997

The effect of nitric oxide and endothelin on skeletal muscle contractility changes when stimulation is altered.

To investigate the effect of endothelial-derived products on the force of contraction of blood-perfused skeletal muscle, we infused S-nitroso-N-acetylpenicillamine (SNAP, 10(-4) M) (a nitric oxide (NO) donor), endothelin-1 (ET-1, 10(-8) M), N-acetylpenicillamine (NAP, 10(-4) M), or saline at a constant vascular concentration into the vascular bed of pump-perfused dog gastrocnemius-plantaris muscles in situ (n = 17). Muscles performed isometric twitch contractions at 0.5, 1.5, and 4 Hz and isometric tetanic contractions (150 ms, 50 Hz) at 12 and 40 contractions/min. We perfused the muscle at a constant pressure at rest and for the first 3 min of the 6-min contraction period, and then switched to constant flow perfusion and infused the substance over the remaining 3 min. Neither NAP nor saline had a significant effect on force of contraction or perfusion pressure. SNAP significantly attenuated developed force as compared with NAP at 40 contractions/min and at 1.5 and 4 Hz. The effect of SNAP on developed force was greater during twitch than tetanic contractions. ET-1 had no significant effect on twitch or tetanic developed force. To test for these results on another mammalian skeletal muscle preparation, we stimulated curarized trimmed mouse soleus in vitro for 500 ms at 50 Hz at either 2 or 4 contractions/min in the presence of SNAP (10(-4) M) or ET-1 (10(-9) M). SNAP, which increased force at 1 contraction/90 s, had no significant effect at the higher contraction frequencies. The inhibition by ET-1 at 2 contractions/min disappeared at 4 contractions/min. Therefore the effect of both NO and ET-1 on mammalian skeletal muscle appears to be dependent upon contraction pattern and frequency.

Animals↗
PubMed1996

Mechanisms within the spinal cord are involved in the movement-induced attenuation of an H reflex in the dog.

1. H reflexes were elicited in the second interosseous muscle of the hindpaw of the anesthetized dog during passive rotation of the shank about the ipsilateral or contralateral knee. Reflexes sampled at four points in the cycle of movement were compared with stationary controls. For both the ipsilateral and contralateral limb manipulations, reflexes were significantly reduced (P < 0.05) across the cycle of movement. Position-related modulation of the reflex amplitude was not detected (P > 0.05) in either instance. 2. The experiments were then repeated after the spinal transection of each animal at the level of T13. Passive rotation about either the ipsilateral or contralateral knee significantly attenuated (P < 0.05) the H reflex across a cycle of movement in the spinal dog. There was little difference in the amount of inhibition produced by the movement between the intact and spinal animals. On average, the reflex was attenuated 29 +/- 2.4% (mean +/- SE) in the intact animals and 32 +/- 2.1% in the spinal animals. 3. It is concluded that passive rotation about the knee of either leg leads to suppression of the H reflex of the second interosseous muscle both in the ipsilateral, moving leg and the contralateral, stationary one. This reflex suppression occurs across the cycle of movement. The mediating circuitry lies within the spinal cord, caudal to T13.

Animals↗
PubMed1996

Cultured dog aortic endothelial cells release vasodilatory products in response to acetylcholine and adenosine.

We tested the hypothesis that products released from contracting skeletal muscle could induce the release of vasodilatory products from vascular endothelium. Superfused endothelium-denuded rabbit aortic and dog femoral artery rings contracted with 1 microM phenylephrine delivered at 1-2 mL/min were subjected to 3-mL bolus challenges that had been briefly exposed to either a culture dish devoid of endothelial cells (control) or a dish containing dog aortic endothelial cells (experimental) immediately prior to their application. Challenges were alternated and included Krebs-Henseleit bicarbonate buffer (Krebs) pH 7.4 (vehicle); 1 microM acetylcholine; and the muscle metabolites 6 mM potassium chloride, 1 mM sodium phosphate monobasic, 10 microM adenosine, acidic Krebs pH 6.8, and 100 microM ammonium chloride. Only the products released from cultured endothelial cells after the addition of acetylcholine and adenosine resulted in a significant relaxation of vascular rings compared with control. Prior incubation of the cultured endothelial cells with 10 microM 8-phenyltheophylline eliminated the relaxation induced by adenosine, and all relaxations were eliminated by prior incubation of the cells with either 10 microM N omega-nitro-L-arginine or a combination of 10 microM indomethacin and 10 microM nordihydroguaiaretic acid. This indicates that at least one metabolite released from contracting skeletal muscle could induce the release of vasodilatory products from the endothelium, which would act as a local amplifier of functional hyperemia.

Acetylcholine↗
PubMed1995

Endothelial cell products alter mammalian skeletal muscle function in vitro.

We tested the hypothesis that endothelin and nitric oxide (NO) alter the force developed by fast-twitch and slow-twitch mammalian skeletal muscle, using a mouse skeletal muscle preparation trimmed to approximately 50% of the original diameter to decrease diffusion distances. We suspended trimmed soleus (SOL) and extensor digitorum longus (EDL) muscles in Krebs-Henseleit buffer (27 degrees C; pH 7.4) gassed with 95% O2 -5% CO2. Muscles were stimulated once every 90 s for 500 ms at 50 Hz for SOL and 100 Hz for EDL. The force developed by trimmed SOL was 223.8 +/- 9.1 mN/mm2 and by EDL was 247.3 +/- 9.4 mN/mm2. Endothelin 1 (ET-1) had no effect on EDL but significantly accelerated the rate of decrease of developed force of SOL at concentrations of 10(-10) mol/L and higher within 10 contractions. When ET-1 was removed, force returned toward control value. Endothelin 3 (ET-3) had no effect on either muscle. S-Nitroso-N-acetylpenicillamine (SNAP), a source of NO, increased developed force over time in both muscles, with a threshold of 10(-6) mol/L. The effect was evident within 5 contractions in both muscles. Force remained elevated above control values after the removal of SNAP. Thus ET-1 attenuated and NO amplified mammalian skeletal muscle function.

Animals↗
PubMed1995

Electrical stimulation and amino acid and ammonia metabolism in the canine gastrocnemius muscle.

This study examined the effects of electrical stimulation on amino acid and ammonia (NH3) metabolism in the isolated in situ canine gastrocnemius muscle preparation. Cut sciatic nerves of 10 mongrel dogs were stimulated at either 3 or 5 twitches/s (10 V, 0.2-ms duration) for 60 min. Muscle NH3 release dramatically increased on stimulation, and over 60 min the 3- and 5-Hz groups released 86.7 +/- 24.2 vs. 160.8 +/- 17.4 mumol.min-1.100 g-1 (P < 0.05) of NH3, respectively. Similarly, the intramuscular NH3 concentration was elevated (P < 0.05) above rest for both groups throughout stimulation, and it was higher (P < 0.05) at 5 min for the 5-Hz (82.7 +/- 2.4 mumol/100 g wet wt) than for the 3-Hz (67.4 +/- 7.4 mumol/100 g wet wt) group. Stimulation was also characterized by a large release of amino acids by both groups. The total amino acid release for 60 min was 415.4 +/- 64.9 vs. 193.3 +/- 56.2 (P < 0.05) mumol/100 g for the 3- and 5-Hz groups, respectively. However, there were no shifts or differences between groups in the intramuscular total amino acid pools. Glutamine (Gln) and alanine (Ala) dominated the amino acids released by muscle and together represented 35 and 46% of the total amino acids released over 60 min for the 3- and 5-Hz groups, respectively. The total release of Gln was higher (P < 0.05) for the 3-Hz (81.1 +/- 5.6 mumol/100 g) than for the 5-Hz (49.4 +/- 10.7 mumol/100 g) group, but there were no differences between groups in total Ala release. In contrast, both groups demonstrated an uptake of branched-chain amino acids (valine, isoleucine, and leucine) after 45 min of stimulation. These data show a stimulation-dependent production of NH3 and release of amino acid by the canine gastrocnemius muscle. These data further show that the degree of net muscle NH3 production is proportional to the frequency, whereas the degree of amino acid release is an inverse function of frequency.

Adenine Nucleotides↗
PubMed1995

Inhibition of canine H reflexes during locomotor-like rotation about the knee arises from muscle mechanoreceptors in quadriceps.

1. H reflexes were elicited in the small muscles of the foot in the canine and human during passive locomotor-like rotation of the shank about the ipsilateral knee. The movement-induced effect was similar in the two species. In the anesthetized dog, the reflex gain was reduced by 36 +/- 8.4% (mean +/- SE) on average, compared with appropriate stationary controls. Reflexes in the human were reduced during movement to 45 +/- 3.5% of their stationary control values. 2. H reflexes were elicited in the anesthetized dog during passive locomotor-like rotation about the knee and were compared with reflexes obtained with the limb stationary. Populations of mechanoreceptors were then systematically removed to ascertain which group or groups provided the sensory input that leads to the decrease in reflex gain during movement. We hypothesized that the majority of the reflex attenuation could be attributed to muscle mechanoreceptors. 3. Reflexes continued to be significantly reduced (P < 0.05) during passive movement about the knee until the muscle mechanoreceptors of the quadriceps muscle group were deactivated. The removal of input from joint receptors or cutaneous receptors did not eliminate the gain reduction induced by the passive movement. 4. It is concluded that muscle mechanoreceptors of the quadriceps muscle group provide an inhibitory input to the H reflex pathway of the dog plantar muscle when the knee is passively moved in a locomotor-like fashion. This source of inhibition likely also contributes to the soleus H reflex gain reduction in humans.

Animals↗
PubMed1995

Blood flow and pressure relationships which determine VO2max.

The role of O2 delivery in regulating VO2max has been studied in an isolated gastrocnemius-plantaris muscle preparation contracting in situ; recent data addressing this issue are presented. VO2 increases nonlinearly with stimulation frequency reaching a peak at 5 twitches.s-1 or 1 tet.s-1 (200 ms trains, 50 imp.s-1). Further increases in stimulation frequency result in a lower VO2. Measured VO2 maxima are less than predicted VO2 capacity, and peak VO2 during tetanic contractions is greater than that during twitches. Above 150 imp.min-1, VO2 is directly related to the level of blood flow attained as VO2/Q (arterial-venous O2 difference) is fixed by some unknown mechanism. Increasing blood flow, with a pump, during 1.s-1 tetanic contractions increases O2 diffusive conductance and peak VO2. When O2 delivery is reduced, ischemic hypoxia appears to result in more rapid reductions in muscle performance than hypoxic hypoxia because of decreases in perfusion pressure and Q. 31P-NMR studies reveal that reductions in creatine phosphate and energy charge are similar between ischemia and hypoxia suggesting a common regulator, O2. We conclude that VO2max is limited by O2 delivery as a result of a limited and uneven distribution of muscle blood flow. These limitations appear secondary to mechanical restraints imposed by contraction duty cycle and vascular compression.

Animals↗
PubMed1994

Cultured endothelial cells from distinct vascular areas show differential responses to agonists.

We compared the ability of cultured endothelial cells isolated from rabbit aorta, vena cava, ventricular chamber, and pulmonary microvasculature to produce relaxing factor(s) in response to acetylcholine (ACh) and bradykinin (BK). Endothelium-denuded rabbit aortic rings were precontracted with 1 microM phenylephrine and superfused at 2 mL/min with Krebs-Henseleit bicarbonate buffer. Rings were exposed to 3-mL bolus control challenges of 1 microM ACh or 1 microM BK. Boluses of ACh or BK were added to dishes of cultured endothelial cells that had been incubated for 45 min in media either with or without 10 microM NG-nitro-L-arginine (NNLA). The resulting solution was applied over the rings within 8 s. Only left ventricular endothelial cells stimulated with ACh and BK, and pulmonary microvascular endothelial cells stimulated with BK produced products that relaxed rings by approximately 6 +/- 2%. Incubation with NNLA attenuated these relaxations. Our findings indicate there are differences in the abilities of endothelial cells of different anatomical origins to release nitric oxide derived relaxing factors in response to ACh and BK.

Acetylcholine↗
PubMed1994

Nitric oxide synthase inhibitors do not alter functional hyperemia in canine skeletal muscle.

To test the hypothesis that endothelium-derived products contribute to functional hyperemia in skeletal muscle, we infused nitric oxide synthase inhibitors, either 200 microM N omega-nitro-L-arginine (NNA) (N = 4) or 1 mM N gamma-monomethyl-L-arginine (NMMA) (N = 4), before and during 6 min of 4 Hz stimulation of canine gastrocnemius in situ. We infused saline (N = 4) as a control. NNA significantly decreased steady-level resting flow by 3.8 +/- 0.4 mL.kg-1.s-1. The increase in flow from rest to 5 min of stimulation was not changed by the nitric oxide synthase inhibitors. We also stimulated muscles for 60 min either with saline infusion (N = 4) or with the infusion of saline during the first 15 min and NNA for the remaining 45 min (n = 4). There was no difference in the flow during contractions. To clarify the effect of these inhibitors on canine vessels, we challenged rings of canine femoral artery with and without endothelium with acetylcholine and bradykinin (both 1 microM) before and after the addition of NNA and NMMA (both 10 microM). The nitric oxide synthase inhibitors decreased the relaxation accompanying acetylcholine. Both inhibitors caused only endothelium-intact rings to contract. Thus, the presence of a nitric oxide synthase inhibitor identified an endothelium-dependent contribution to the regulation of blood flow to skeletal muscle at rest but had no effect on functional hyperemia.

Acetylcholine↗
PubMed1994

Effect of nitroprusside and endothelium-derived products on slow-twitch skeletal muscle function in vitro.

We tested the hypothesis that the products of endothelial cells alter the force developed by skeletal muscle. Since these products have a very short half-life and are produced in a low concentration, we developed a superfused muscle preparation in which the mouse soleus (SOL) was superfused at 10.5 mL/min with Krebs-Henseleit buffer (KH) (27 degrees C; pH 7.4), gassed with 95% O2-5% CO2. To evaluate this preparation, we compared the superfused muscles with muscles submerged in a bath. All muscles were stimulated at 50 Hz for 500 ms once every 30 s. Submerged SOL developed 275 +/- 15 mN/mm2, while the superfused muscles developed 271 +/- 15 mN/mm2. Both submerged and superfused SOL consistently increased rest tension to a 3-mL bolus of 25 mM caffeine and decreased developed force when exposed to a 3-mL bolus of 30 mM diprotonated phosphate (pH 6.4). We then exposed superfused SOL to 3 mL bolus injections of KH, 1 microM acetylcholine, 30 mM nitroprusside (a source of nitric oxide), and the supernatant from dishes of cultured endothelial cells from rabbit aorta challenged with acetylcholine. Nitroprusside and the supernatant significantly improved force maintenance, compared with KH and acetylcholine, respectively. Since the supernatant should contain products of endothelial cells, these products appear to have a positive effect on contractile function in slow-twitch skeletal muscle that is similar to the effect of nitric oxide.

Acetylcholine↗
PubMed1991

Free radicals may contribute to oxidative skeletal muscle fatigue.

We used mouse soleus in vitro (n = 30) and canine gastrocnemius-plantaris preparations (n = 20) pump-perfused at the animal's blood pressure to establish if free radicals contribute to fatigue in oxidative skeletal muscle. The soleus from each leg contracted for 200 ms (70 Hz) once every minute for 60 min in Hepes buffer gassed with 100% oxygen at 27 degrees C. When contracting in Hepes alone, both muscles fatigued at 0.9 mN/mm2.min over the 60 min. The addition of purines to the bath increased the rate to 1.4 mN/mm2.min and the addition of xanthine oxidase to generate free radicals increased the rate again to 1.9 mN/mm2.min. Thus free radicals appeared to attenuate oxidative skeletal muscle function. Each canine muscle contracted isometrically at 4 Hz for 30 min and then rested for 45 min before contracting for a second 30 min at 4 Hz. In each experiment, we infused saline at 0.76 mL/min into resting muscle and at 1.91 mL/min during the first contraction period. During the remainder of the experiment, we infused, at the same rates, saline (n = 4), 10 microM dimethyl sulfoxide (DMSO) (n = 4) to identify the effect of scavenging hydroxyl radicals, 1 mM allopurinol to establish the effect of blocking xanthine oxidase (n = 4), or 200 microM desferoxamine to determine the effect of chelating iron (n = 4). With saline, the fatigue rate over the 30 min of contractions increased from 5.0 +/- 0.2 to 6.3 +/- 0.5 N/kg.min from the first to the second stimulation period. The fatigue rate was slower in the second period with each of the three experimental substances (DMSO, 5.9 +/- 0.8 to 3.2 +/- 0.3; allopurinol, 7.3 +/- 1.1 to 4.6 +/- 0.6; desferoxamine, 6.8 +/- 0.8 to 4.4 +/- 0.8 N/kg.min). The fatigue rate was the same as control when DMSO was infused only during the second contraction period. Therefore, free radicals appeared to contribute to fatigue in oxidative skeletal muscle.

Animals↗