Progressive decrease of intramyocellular accumulation of H+ and Pi in human skeletal muscle during repeated isotonic exercise

The purpose of this study was to evaluatethe hypotheses that accumulation of hydrogen ions and/or inorganicphosphate (Pi) in skeletal muscle increases with repeated bouts ofisotonic exercise. ³¹P-Magnetic resonance spectroscopy wasused to examine the gastrocnemius muscle of seven highly aerobicallytrained females during four bouts of isotonic plantar flexion. Theexercise bouts (EX1-4) of 3 min and 18 swere separated by 3 min and 54 s of complete rest. Muscle ATP did notchange during the four bouts. Phosphocreatine (PCr) degradation duringEX1 (13.3 ± 2.4 mmol/kg wet weight) was higher(P < 0.01) compared with EX3-4(9.7 ± 1.6 and 9.6 ± 1.8 mmol/kg wet weight, respectively).The intramyocellular pH at the end of EX1 (6.87 ± 0.05) was significantly lower (P < 0.001) than thoseof EX2 (6.97 ± 0.02), EX3 (7.02 ± 0.01), and EX4 (7.02 ± 0.02). Total Pi anddiprotonated Pi were significantly higher (P < 0.001)at the end of EX1 (17.3 ± 2.7 and 7.8 ± 1.6 mmol/kg wet weight, respectively) compared with the values at the end of EX3 and EX4. The monoprotonated Pi at the endof EX1 (9.5 ± 1.2 mmol/kg wet weight) was alsosignificantly higher (P < 0.001) than that afterEX4 (7.5 ± 1.1 mmol/kg wet weight). Subjects' ratingof perceived exertion increased (P < 0.001) towardexhaustion as the number of exercises progressed (7.1 ± 0.4, EX1; 8.0 ± 0.3, EX2; 8.5 ± 0.3, EX3; and 9.0 ± 0.4, EX4; scale from 0 to10). The present results indicate that human muscle fatigue during repeated intense isotonic exercise is not due to progressive depletion of high energy phosphates nor to intracellular accumulation of hydrogenions, total, mono-, or diprotonated Pi.

     

Impaired calcium pump function does not slow relaxation in human skeletal muscle after prolonged exercise

Booth, John, Michael J. McKenna, Patricia A. Ruell, Tom H. Gwinn, Glen M. Davis, Martin W. Thompson, Alison R. Harmer, Sandra K. Hunter, and John R. Sutton. Impaired calcium pump function doesnot slow relaxation in human skeletal muscle after prolonged exercise.J. Appl. Physiol. 83(2): 511-521, 1997.This study examined the effects of prolonged exercise on humanquadriceps muscle contractile function and homogenate sarcoplasmicreticulum Ca²⁺ uptake andCa²⁺-adenosinetriphosphataseactivity. Ten untrained men cycled at 75 ± 2% (SE) peak oxygenconsumption until exhaustion. Biopsies were taken from theright vastus lateralis muscle at rest, exhaustion, and 20 and 60 minpostexercise. Peak tension and half relaxation time of the leftquadriceps muscle were measured during electrically evoked twitch andtetanic contractions and a maximal voluntary isometric contraction atrest, exhaustion, and 10, 20, and 60 min postexercise. At exhaustion,homogenate Ca²⁺ uptake andCa²⁺ adenosinetriphosphataseactivity were reduced by 17 ± 4 and 21 ± 5%, respectively, andremained depressed after 60 min recovery (P  0.01). Muscle ATP, creatinephosphate, and glycogen were all depressed at exhaustion(P  0.01). Peak tension during a maximal voluntary contraction, a twitch, and a 10-Hz stimulation werereduced after exercise by 28 ± 3, 45 ± 6, 65 ± 5%,respectively (P  0.01), but noslowing of half relaxation times were found. Thus fatigue induced byprolonged exercise reduced muscleCa²⁺ uptake, but this did notcause a slower relaxation of evoked contractions.

     

Alternate activity in the synergistic muscles during prolonged low-level contractions

The purpose ofthis study was to investigate the functional interrelationship betweensynergistic muscle activities during low-level fatiguing contractions.Six human subjects performed static and dynamic contractions at anankle joint angle of 110° plantar flexion and within the range of90-110° (anatomic position = 90°) under constant load(10% maximal voluntary contraction) for 210 min. Surfaceelectromyogram records from lateral gastrocnemius (LG), medialgastrocnemius (MG), and soleus (Sol) muscles showed high and silentactivities alternately in the three muscles and a complementary andalternate activity between muscles in the time course. In the secondhalf of all exercise times, the number of changes in activity increasedsignificantly (P < 0.05) in each muscle. The ratios of active to silent periods of electromyogram activity were significantly higher (P < 0.05) in MG (4.5 ± 2.2) and Sol (4.3 ± 2.8) than in the LG(0.4 ± 0.1), but no significant differences were observed betweenMG and Sol. These results suggest that the relativeactivation of synergistic motor pools are not constant during alow-level fatiguing task.

     

Effects of short-term inactivity on glucose tolerance, energy expenditure, and blood flow in trained subjects

The purpose of this investigation was to examinethe effects of 7-10 days of inactivity (IA) on glucose tolerance(GT), resting metabolic rate (RMR), thermic effect of a meal (TEM), andlimb blood flow in endurance-trained men. Eight highly trained (peak O₂ consumption 64 ± 2 ml · kg¹ · min¹)endurance athletes participated in this study involving two identicaltest days, one ~24 h after a normal training bout (Tr) and the secondafter 7-10 days of IA. The following tests were conducted at eachvisit: 75-g oral glucose tolerance test (OGTT), RMR, and TEM andmeasurements of calf and forearm blood flow (BF) by using venousocclusive plethysmography. Body weight remained unchangedduring this short period of IA (Tr, 78.5 ± 1 kg; IA, 78.7 ± 1 kg). The area under the glucose and insulin curves increased 65% (Tr,3,375 ± 877 vs. IA, 5,559.4 ± 621 mg · dl¹ · 180 min¹) and 73% (Tr,2,182.5 ± 270 vs. IA, 3,793.1 ± 739 µU · ml¹ · 180 min¹) after IA,respectively (P < 0.01). RMRdecreased significantly (4%; 1.5 ± 0.02 vs. 1.44 ± 0.02 kcal/min; P < 0.05) and respiratory exchange ratio during the OGTT increased (4%, 0.812 ± 0.011 vs. 0.842 ± 0.009; P < 0.05) afterIA, whereas TEM increased similarly in the Tr and IA states. In the Trstate, mean calf BF increased by 22% (3.17 ± 0.22 vs. 3.87 ± 0.38 ml · 100 ml¹ · min¹;P < 0.05) during the OGTT butremained unchanged after IA, whereas no differences at rest or duringOGTTs existed between the two conditions for forearm BF. Incrementalinsulin area above fasting during the OGTT was correlated with meancalf BF in the Tr (r = 0.76, P < 0.05) and IA(r = 0.72, P < 0.05) states. In conclusion, 7-10 days of IA results in a deterioration in GT and a reduction in RMR. After glucose ingestion, calf BF was elevated compared withresting levels in the Tr state but was unchanged in the IA state;however, limb BF was not related to GT or RMR. Thus our findings raisequestions regarding the relative contribution of BF in modulatingglucose tolerance and energy expenditure in endurance athletes in theirhabitual Tr or IA state.

     

Postnatal expression and activity of the mitochondrial 2-oxoglutarate-malate carrier in intact hearts

This studyexamines the functional implications of postnatal changes in theexpression of the mitochondrial transporter protein, 2-oxoglutarate-malate carrier (OMC). Online ¹³C nuclearmagnetic resonance (¹³C NMR) measurements of isotopekinetics in hearts from neonate (3-4 days) and adult rabbitsprovided tricarboxylic acid cycle flux rates and flux rates throughOMC. Neonate and adult hearts oxidizing 2.5 mM[2,4-¹³C₂]butyrate were subjected toeither normal or high cytosolic redox state (2.5 mM lactate) conditionsto evaluate the recruitment of malate-aspartate activity and theresulting OMC flux. During development from neonate (3-4 days) toadult, mitochondrial protein density in the heart increased from19 ± 3% to 31 ± 2%, whereas OMC expression decreased by65% per mitochondrial protein content (P < 0.05).Correspondingly, OMC flux was lower in adults hearts than in neonatesby 73% (neonate = 7.4 ± 0.4, adult = 2.0 ± 0.1 µmol/min per 100 mg mitochondrial protein; P < 0.05). Despite clear changes in OMC content and flux, theresponsiveness of the malate-aspartate shuttle to increased cytosolicNADH was similar in both adults and neonates with an approximatethreefold increase in OMC flux (in densitometric units/100 mgmitochondrial protein: neonate = 25.8 ± 2.5, adult = 6.0 ± 0.2; P < 0.05). The¹³C NMR data demonstrate that OMC activity is a principalcomponent of the rate of labeling of glutamate.

     

Functional aspects of skeletal muscle contractile apparatus and sarcoplasmic reticulum after fatigue

This study examined the effects of fatigue on the functionalaspects of the contractile apparatus and sarcoplasmic reticulum (SR).Frog semitendinosus muscles were stimulated to fatigue, and skinnedfibers or a homogenate fraction was prepared from both fatigued andrested contralateral muscles. In fatigued fibers, maximalCa²⁺-activated force of thecontractile apparatus was unaltered, whereas maximal actomyosin-ATPaseactivity was depressed by 20%. TheCa²⁺ sensitivity of force wasincreased, whereas that of actomyosin-ATPase was not altered. Also, therate constant for tension redevelopment was decreased at submaximalCa²⁺ concentration. These latterfindings suggest that fatigue slows the dissociation offorce-generating myosin cross bridges.Ca²⁺ uptake andCa²⁺-ATPase activity of the SRwere depressed by 46 and 21%, respectively, in the fatigued muscles.Fatigue also reduced the rates of SR Ca²⁺ release evoked byAgNO₃ and4-chloro-m-cresol by 38 and 45%, respectively. During fatigue, the contractile apparatus and SR undergointrinsic functional alterations. These changes likely result inaltered force production and energy consumption by the intact muscle.

     

Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training

McCall, G. E., W. C. Byrnes, A. Dickinson, P. M. Pattany,and S. J. Fleck. Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training.J. Appl. Physiol. 81(5):2004-2012, 1996.Twelve male subjects with recreationalresistance training backgrounds completed 12 wk of intensifiedresistance training (3 sessions/wk; 8 exercises/session; 3 sets/exercise; 10 repetitions maximum/set). All major muscle groupswere trained, with four exercises emphasizing the forearm flexors.After training, strength (1-repetition maximum preacher curl) increasedby 25% (P < 0.05). Magneticresonance imaging scans revealed an increase in the biceps brachiimuscle cross-sectional area (CSA) (from 11.8 ± 2.7 to 13.3 ± 2.6 cm²;n = 8;P < 0.05). Muscle biopsies of thebiceps brachii revealed increases(P < 0.05) in fiber areas for type I(from 4,196 ± 859 to 4,617 ± 1,116 µm²;n = 11) and II fibers (from 6,378 ± 1,552 to 7,474 ± 2,017 µm²;n = 11). Fiber number estimated fromthe above measurements did not change after training (293.2 ± 61.5 × 10³ pretraining; 297.5 ± 69.5 × 10³ posttraining;n = 8). However, the magnitude ofmuscle fiber hypertrophy may influence this response because thosesubjects with less relative muscle fiber hypertrophy, but similarincreases in muscle CSA, showed evidence of an increase in fibernumber. Capillaries per fiber increased significantly(P < 0.05) for both type I(from 4.9 ± 0.6 to 5.5 ± 0.7;n = 10) and II fibers (from 5.1 ± 0.8 to 6.2 ± 0.7; n = 10). Nochanges occurred in capillaries per fiber area or muscle area. Inconclusion, resistance training resulted in hypertrophy of the totalmuscle CSA and fiber areas with no change in estimated fiber number,whereas capillary changes were proportional to muscle fiber growth.

     

Forearm training attenuates sympathetic responses to prolonged rhythmic forearm exercise

Sinoway, Lawrence, Jeffrey Shenberger, Gretchen Leaman,Robert Zelis, Kristen Gray, Robert Baily, and Urs Leuenberger. Forearm training attenuates sympathetic responses to prolonged rhythmic forearm exercise. J. Appl.Physiol. 81(4): 1778-1784, 1996.We previouslydemonstrated that nonfatiguing rhythmic forearm exercise at 25%maximal voluntary contraction (12 2-s contractions/min) evokessympathoexcitation without significant engagement ofmetabolite-sensitive muscle afferents (B. A. Batman, J. C. Hardy, U. A. Leuenberger, M. B. Smith, Q. X. Yang, and L. I. Sinoway.J. Appl. Physiol. 76: 1077-1081,1994). This is in contrast to the sympathetic nervous system responsesobserved during fatiguing static forearm exercise wheremetabolite-sensitive afferents are the key determinants of sympatheticactivation. In this report we examined whether forearm exercisetraining would attenuate sympathetic nervous system responses torhythmic forearm exercise. We measured heart rate, mean arterial bloodpressure (MAP), muscle sympathetic nerve activity (microneurography),plasma norepinephrine (NE), and NE spillover and clearance (tritiatedNE kinetics) during nonfatiguing rhythmic forearm exercise before andafter a 4-wk unilateral forearm training paradigm. Training had noeffect on forearm mass, maximal voluntary contraction, or heart ratebut did attenuate the increase in MAP (increase in MAP: from 15.2 ± 1.8 before training to 11.4 ± 1.4 mmHg after training;P < 0.017), muscle sympathetic nerve activity (increase in bursts: from 10.8 ± 1.4 before training to6.2 ± 1.1 bursts/min after training;P < 0.030), and the NE spillover(increase in arterial spillover: from 1.3 ± 0.2 before training to0.6 ± 0.2 nmol ^· min^{1 ·} m²after training, P < 0.014; increasein venous spillover: from 2.0 ± 0.6 beforetraining to 1.0 ± 0.5 nmol ^· min^{1 ·} m²after training, P < 0.037) seen inresponse to exercise performed by the trained forearm. Thus forearmtraining reduces sympathetic responses during a nonfatiguing rhythmichandgrip paradigm that does not engage muscle metaboreceptors. Wespeculate that this effect is due to a conditioning-inducedreduction in mechanically sensitive muscle afferentdischarge.

     

Effects of the ovarian cycle on sympathetic neural outflow during static exercise

We comparedreflex responses to static handgrip at 30% maximal voluntarycontraction (MVC) in 10 women (mean age 24.1 ± 1.7 yr) during twophases of their ovarian cycle: the menstrual phase (days 1-4) and the follicularphase (days10-12). Changes in muscle sympathetic nerve activity (MSNA; microneurography) in response tostatic exercise were greater during the menstrual compared withfollicular phase (phase effect P = 0.01). Levels of estrogen were less during the menstrual phase(75 ± 5.5 vs. 116 ± 9.6 pg/ml, days 1-4 vs.days 10-12;P = 0.002). Generated tension did not explain differences in MSNA responses (MVC: 29.3 ± 1.3 vs. 28.2 ± 1.5 kg, days 1-4 vs.days 10-12;P = 0.13). In a group of experiments with the use of ³¹P-NMRspectroscopy, no phase effect was observed forH⁺ andH₂PO₄ concentrations(n = 5). During an ischemicrhythmic handgrip paradigm (20% MVC), a phase effect was notobserved for MSNA or H⁺ orH₂PO₄ concentrations,suggesting that blood flow was necessary for the expression of thecycle-related effect. The present studies suggest that, during statichandgrip exercise, MSNA is increased during the menstrual compared withthe follicular phase of the ovarian cycle.

     

Force generation,but not myosin ATPase activity,declines with age in rat muscle fibers

We tested the hypothesis thatage-associated decline in muscle function is related to a change inmyosin ATPase activity. Single, glycerinated semimembranosus fibersfrom young (8-12 mo) and aged (32-37 mo) Fischer 344 × Brown Norway male rats were analyzed simultaneously for force andmyosin ATPase activity over a range of Ca²⁺ concentrations.Maximal force generation was ~20% lower in fibers from aged animals(P = 0.02), but myosin ATPase activity was not different between fibers from young and aged rats: 686 ± 46 (n = 30) and 697 ± 46 µM/s (n = 33) (P = 0.89). The apparent rate constant for thedissociation of strong-binding myosin from actin was calculated to be~30% greater in fibers from aged animals (P = 0.03),indicating that the lower force produced by fibers from aged animals isdue to a greater flux of myosin heads from the strong-binding state tothe weak-binding state during contraction. This is in agreement withour previous electron paramagnetic resonance experiments that showed areduced fraction of myosin heads in the strong-binding state during amaximal isometric contraction in fibers from older rats.

     

Effects of load and tone on the mechanics of isolated human bronchial smooth muscle

Isotonic and isometric properties of nine human bronchial smoothmuscles were studied under various loading and tone conditions. Freshlydissected bronchial strips were electrically stimulated successively atbaseline, after precontraction with10⁷ M methacholine (MCh),and after relaxation with10⁵ M albuterol (Alb).Resting tension, i.e., preload determining optimal initial length(L_o) atbaseline, was held constant. Compared with baseline, MCh decreasedmuscle length to 93 ± 1%L_o(P < 0.001) before any electricalstimulation, whereas Alb increased it to 111 ± 3%L_o(P < 0.01). MCh significantlydecreased maximum unloaded shortening velocity (0.045 ± 0.007 vs.0.059 ± 0.007 L_o/s), maximalextent of muscle shortening (8.4 ± 1.2 vs. 13.9 ± 2.4%L_o), and peakisometric tension (6.1 ± 0.8 vs. 7.2 ± 1.0 mN/mm²). Alb restored all thesecontractile indexes to baseline values. These findings suggest that MChreversibly increased the number of active actomyosin cross bridgesunder resting conditions, limiting further muscle shortening and activetension development. After the electrically induced contraction,muscles showed a transient phase of decrease in tension below preload.This decrease in tension was unaffected by afterload levels but wassignificantly increased by MCh and reduced by Alb. These findingssuggest that the cross bridges activated before, but not during, theelectrically elicited contraction may modulate the phase of decrease intension below preload, reflecting the active part of resting tension.     

Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle

Edwards, N., I. Wilcox, O. J. Polo, and C. E. Sullivan.Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle. J. Appl.Physiol. 81(5): 2142-2146, 1996.We investigatedthe cardiovascular responses to acute hypercapnia during the menstrualcycle. Eleven female subjects with regular menstrual cycles performedhypercapnic rebreathing tests during the follicular and luteal phasesof their menstrual cycles. Ventilatory and cardiovascular variableswere recorded breath by breath. Serum progesterone and estradiol weremeasured on each occasion. Serum progesterone was higher during theluteal [50.4 ± 9.6 (SE) nmol/l] than during thefollicular phase (2.1 ± 0.7 nmol/l;P < 0.001), but serum estradiol didnot differ (follicular phase, 324 ± 101 pmol/l; luteal phase, 162 ± 71 pmol/l; P = 0.61). Thesystolic blood pressure responses during hypercapnia were 2.0 ± 0.3 and 4.0 ± 0.5 mmHg/Torr (1 Torr = 1 mmHg rise inend-tidal PCO₂) during the follicularand luteal phases, respectively, of the menstrual cycle(P < 0.01). The diastolic bloodpressure responses were 1.1 ± 0.2 and 2.1 ± 0.3 mmHg/Torrduring the follicular and luteal phases, respectively(P < 0.002). Heart rate responses did not differ during the luteal (1.7 ± 0.3 beats ^· min^{1 ·} Torr¹)and follicular phases (1.4 ± 0.3 beats ^· min^{1 ·} Torr¹;P = 0.59). These data demonstrate agreater pressor response during the luteal phase of the menstrual cyclethat may be related to higher serum progesterone concentrations.

     

Neuromuscular factors contributing to in vivo eccentric moment generation

Webber, Sandra, and Dean Kriellaars. Neuromuscularfactors contributing to in vivo eccentric moment generation.J. Appl. Physiol. 83(1): 40-45, 1997.Muscle series elasticity and its contribution to eccentricmoment generation was examined in humans. While subjects [male,n = 30; age 26.3 ± 4.8 (SD) yr; body mass 78.8 ± 13.1 kg] performed an isometric contractionof the knee extensors at 60° of knee flexion, a quick stretch was imposed with a 12°-step displacement at 100°/s. The test wasperformed at 10 isometric activation levels ranging from 1.7 to 95.2%of maximal voluntary contraction (MVC). A strong linear relationship was observed between the peak imposed eccentric moment derived fromquick stretch and the isometric activation level(y = 1.44x + 7.08; r = 0.99). This increase in theeccentric moment is consistent with an actomyosin-dependent elasticitylocated in series with the contractile element of muscle. Byextrapolating the linear relationship to 100% MVC, the predictedmaximum eccentric moment was found to be 151% MVC, consistent with invitro data. A maximal voluntary, knee extensor strength test was alsoperformed (5-95°, 3 repetitions, ±50, 100, 150, 200, and250°/s). The predicted maximum eccentric moment was 206% of theangle- and velocity-matched, maximal voluntary eccentric moments. Thiswas attributed to a potent neural regulatory mechanism that limits therecruitment and/or discharge of motor units during maximalvoluntary eccentric contractions.

     

Effects of hindlimb contraction on pressor and muscle interstitial metabolite responses in the cat

We used the microdialysis technique to measurethe interstitial concentration of several putative metabolic stimulantsof the exercise pressor reflex during 3- and 5-Hz twitch contractions in the decerebrate cat. The peak increases in heart rate and mean arterial pressure during contraction were 20 ± 5 beats/min and 21 ± 8 mmHg and 27 ± 9 beats/min and 37 ± 12 mmHg for the 3- and 5-Hz stimulation protocols, respectively. All variables returned tobaseline after 10 min of recovery. Interstitial lactate rose (P < 0.05) by 0.41 ± 0.15 and0.56 ± 0.16 mM for the 3- and 5-Hz stimulation protocols,respectively, and were not statistically different from one another.Interstitial lactate levels remained above(P < 0.05) baseline during recoveryin the 5-Hz group. Dialysate phosphate concentrations (corrected forshifts in probe recovery) rose with stimulation(P < 0.05) by 0.19 ± 0.08 and0.11 ± 0.03 mM for the 3- and 5-Hz protocols. There were nodifferences between groups. The resting dialysateK⁺ concentrations for the 3- and5-Hz conditions were 4.0 ± 0.1 and 3.9 ± 0.1 meq/l,respectively. During stimulation the dialysate K⁺ concentrations rose steadilyfor both conditions, and the increase from rest to stimulation(P < 0.05) was 0.57 ± 0.19 and0.81 ± 0.06 meq/l for the 3- and 5-Hz conditions, respectively,with no differences between groups. Resting dialysate pH was6.915 ± 0.055 and 6.981 ± 0.032 and rose to 7.013 (P < 0.05) and 7.053 (P < 0.05) for the 3- and 5-Hzconditions, respectively, and then became acidotic (6.905, P < 0.05) during recovery (5 Hzonly). This study represents the first time simultaneous measurements of multiple skeletal muscle interstitial metabolites and pressor responses to twitch contractions have been made in the cat. These datasuggest that interstitial K⁺ andphosphate, but not lactate and H⁺,may contribute to the stimulation of thin fiber muscle afferents duringcontraction.

     

Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic reflex

Ray, Chester A., and Keith M. Hume. Neck afferents andmuscle sympathetic activity in humans: implications for the vestibulosympathetic reflex. J. Appl.Physiol. 84(2): 450-453, 1998.We have shownpreviously that head-down neck flexion (HDNF) in humans elicitsincreases in muscle sympathetic nerve activity (MSNA). The purpose ofthis study was to determine the effect of neck muscle afferents onMSNA. We studied this question by measuring MSNA before and after headrotation that would activate neck muscle afferents but not thevestibular system (i.e., no stimulation of the otolith organs orsemicircular canals). After a 3-min baseline period with the head inthe normal erect position, subjects rotated their head to the side(~90°) and maintained this position for 3 min. Head rotation wasperformed by the subjects in both the prone(n = 5) and sitting(n = 6) positions. Head rotation did not elicit changes in MSNA. Average MSNA, expressed asburst frequency and total activity, was 13 ± 1 and 13 ± 1 bursts/min and 146 ± 34 and 132 ± 27 units/min during baselineand head rotation, respectively. There were no significant changes incalf blood flow (2.6 ± 0.3 to 2.5 ± 0.3 ml · 100 ml¹ · min¹;n = 8) and calf vascular resistance(39 ± 4 to 41 ± 4 units; n = 8). Heart rate (64 ± 3 to 66 ± 3 beats/min;P = 0.058) and mean arterial pressure(90 ± 3 to 93 ± 3; P < 0.05)increased slightly during head rotation. Additional neck flexionstudies were performed with subjects lying on their side(n = 5). MSNA, heart rate, and meanarterial pressure were unchanged during this maneuver, which also doesnot engage the vestibular system. HDNF was tested in 9 of the 13 subjects. MSNA was significantly increased by 79 ± 12% (P < 0.001) during HDNF. Thesefindings indicate that neck afferents activated by horizontal neckrotation or flexion in the absence of significant force development donot elicit changes in MSNA. These findings support the concept thatHDNF increases MSNA by the activation of the vestibular system.

     

Microdialysis ethanol removal reflects probe recovery rather than local blood flow in skeletal muscle

The present study compared the microdialysis ethanoloutflow-inflow technique for estimating blood flow (BF) in skeletalmuscle of humans with measurements by Doppler ultrasound of femoralartery inflow to the limb(BF_FA). The microdialysis probeswere inserted in the vastus lateralis muscle and perfused with a Ringeracetate solution containing ethanol,[2-³H]adenosine (Ado),andD-[¹⁴C(U)]glucose.BF_FA at rest increased from0.16 ± 0.02 to 1.80 ± 0.26 and 4.86 ± 0.53 l/minwith femoral artery infusion of Ado (Ado_FA,i) at 125 and 1,000 µg · min¹ · l¹thigh volume (low dose and high dose, respectively;P < 0.05) and to 3.79 ± 0.37 and6.13 ± 0.65 l/min during one-legged, dynamic, thigh muscle exercisewithout and with high Ado_FA,i,respectively (P < 0.05). The ethanoloutflow-to-inflow ratio (38.3 ± 2.3%) and the probe recoveries(PR) for [2-³H]Ado(35.4 ± 1.6%) and forD-[¹⁴C(U)]glucose(15.9 ± 1.1%) did not change withAdo_FA,i at rest (P = not significant). During exercisewithout and with Ado_FA,i, theethanol outflow-to-inflow ratio decreased(P < 0.05) to a similar level of17.5 ± 3.4 and 20.6 ± 3.2%, respectively(P = not significant), respectively,while the PR increased (P < 0.05) toa similar level (P = not significant)of 55.8 ± 2.8 and 61.2 ± 2.5% for[2-³H]Ado and to 42.8 ± 3.9 and 45.2 ± 5.1% forD-[¹⁴C(U)]glucose.Whereas the ethanol outflow-to-inflow ratio and PR correlated inverselyand positively, respectively, to the changes in BF during muscularcontractions, neither of the ratio nor PR correlated tothe Ado_FA,i-induced BF increase.Thus the ethanol outflow-to-inflow ratio does not represent skeletalmuscle BF but rather contraction-induced changes in molecular transport in the interstitium or over the microdialysis membrane.

     

Fuel metabolism in men and women during and after long-duration exercise

This study aimed to determine gender-baseddifferences in fuel metabolism in response to long-duration exercise.Fuel oxidation and the metabolic response to exercise were compared inmen (n = 14) and women(n = 13) during 2 h (40% of maximalO₂ uptake) of cycling and 2 h ofpostexercise recovery. In addition, subjects completed a separatecontrol day on which no exercise was performed. Fuel oxidation wasmeasured using indirect calorimetry, and blood samples were drawn forthe determination of circulating substrate and hormone levels. Duringexercise, women derived proportionally more of the total energyexpended from fat oxidation (50.9 ± 1.8 and 43.7 ± 2.1% forwomen and men, respectively, P < 0.02), whereas men derived proportionally more energy from carbohydrateoxidation (53.1 ± 2.1 and 45.7 ± 1.8% for men and women,respectively, P < 0.01). Thesegender-based differences were not observed before exercise, afterexercise, or on the control day. Epinephrine(P < 0.007) and norepinephrine(P < 0.0009) levels weresignificantly greater during exercise in men than in women (peakepinephrine concentrations: 208 ± 36 and 121 ± 15 pg/ml in menand women, respectively; peak norepinephrine concentrations: 924 ± 125 and 659 ± 68 pg/ml in men and women, respectively). Ascirculating glycerol levels were not different between the two groups,this suggests that women may be more sensitive to the lipolytic action of the catecholamines. In conclusion, these data support the view thatdifferent priorities are placed on lipid and carbohydrate oxidationduring exercise in men and women and that these gender-based differences extend to the catecholamine response to exercise.

     

K+ supplementation increases muscle [Na+-K+-ATPase] and improves extrarenal K+ homeostasis in rats

Bundgaard, Henning, Thomas A. Schmidt, Jim S. Larsen, andKeld Kjeldsen. K⁺supplementation increases muscle[Na⁺-K⁺-ATPase]and improves extrarenal K⁺homeostasis in rats. J. Appl. Physiol.82(4): 1136-1144, 1997.Effects ofK⁺ supplementation (~200 mmolKCl/100 g chow) on plasma K⁺,K⁺ content, andNa⁺-K⁺-adeonsinetriphosphatase(ATPase) concentration([Na⁺-K⁺-ATPase])in skeletal muscles as well as on extrarenalK⁺ clearance were evaluated inrats. After 2 days of K⁺supplementation, hyperkalemia prevailed(K⁺-supplemented vs.weight-matched control animals) [5.1 ± 0.2 (SE) vs. 3.2 ± 0.1 mmol/l, P < 0.05, n = 5-6], and after 4 daysa significant increase in K⁺content was observed in gastrocnemius muscle (104 ± 2 vs. 97 ± 1 µmol/g wet wt, P < 0.05, n = 5-6). After 7 days ofK⁺ supplementation, a significantincrease in[³H]ouabain bindingsite concentration (344 ± 5 vs. 239 ± 8 pmol/g wet wt,P < 0.05, n = 4) was observed in gastrocnemiusmuscle. After 2 wk, increases in plasmaK⁺,K⁺ content, and[³H]ouabain bindingsite concentration in gastrocnemius muscle amounted to 40, 8, and 68%(P < 0.05) above values observed inweight-matched control animals, respectively. The latter change wasconfirmed by K⁺-dependentp-nitrophenyl phosphatase activitymeasurements. Fasting for 1 day reduced plasmaK⁺ andK⁺ content in gastrocnemius musclein rats that had been K⁺supplemented for 2 wk by 3.1 ± 0.3 mmol/l(P < 0.05, n = 5) and 15 ± 2 µmol/g wet wt(P < 0.05, n = 5), respectively. After induction of anesthesia, arterial plasma K⁺was measured during intravenous KCl infusion (0.75 mmolKCl · 100 g bodywt¹ · h¹).The K⁺-supplemented fasted groupdemonstrated a 42% (P < 0.05) lower plasma K⁺ rise, associated with asignificantly higher increase inK⁺ content in gastrocnemius muscleof 7 µmol/g wet wt (P < 0.05, n = 5) compared with their controlanimals. In conclusion, K⁺supplementation increases plasmaK⁺,K⁺ content, and[Na⁺-K⁺-ATPase]in skeletal muscles and improves extrarenalK⁺ clearance capacity.

     

Effects of emphysema on diaphragm blood flow during exercise

Chronichyperinflation of the lung in emphysema displaces the diaphragmcaudally, thereby placing it in a mechanically disadvantageous positionand contributing to the increased work of breathing. We tested thehypothesis that total and regional diaphragm blood flows are increasedin emphysema, presumably reflecting an increased diaphragm energeticdemand. Male Syrian Golden hamsters were randomly divided intoemphysema (E; intratracheal elastase 25 units/100 g body wt) andcontrol (C; saline) groups, and experiments were performed 16-20wk later. The regional distribution of blood flow withinthe diaphragm was determined by using radiolabeled microspheres inhamsters at rest and during treadmill exercise (walking at 20 feet/min,20% grade). Consistent with pronounced emphysema, lung volume per unitbody weight was greater in E hamsters (C, 59.3 ± 1.8; E, 84.5 ± 5.0 ml/kg; P < 0.001) and arterialPO₂ was lower both at rest (C, 74 ± 3; E, 59 ± 2 Torr; P < 0.001) and during exercise (C, 93 ± 3; E, 69 ± 4 Torr; P < 0.001). At rest, total diaphragm blood flow was not different between C and Ehamsters (C, 47 ± 4; E, 38 ± 4 ml · min¹ · 100 g¹;P = 0.18). In both C and E hamsters,blood flow at rest was lower in the ventral costal region of thediaphragm than in the dorsal and medial costal regions and the cruraldiaphragm. During exercise in both C and E hamsters, blood flowsincreased more in the dorsal and medial costal regions and in thecrural diaphragm than in the ventral costal region. Total diaphragmblood flow was greater in E hamsters during exercise (C, 58 ± 7; E,90 ± 14 ml · min¹ · 100 g¹;P = 0.03), as a consequence ofsignificantly higher blood flows in the medial and ventral costalregions and crural diaphragm. In addition, exercise-induced increasesin intercostal (P < 0.005) andabdominal (P < 0.05) muscle bloodflows were greater in E hamsters. The finding that diaphragm blood flowwas greater in E hamsters during exercise supports the contention thatemphysema increases the energetic requirements of the diaphragm.

     

Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity

Skeletal muscle oxidative enzyme capacity is impaired inpatients suffering from emphysema and chronic obstructive pulmonary disease. This effect may result as a consequence of the physiological derangements because of the emphysema condition or, alternatively, as aconsequence of the reduced physical activity level in these patients.To explore this issue, citrate synthase (CS) activity was measured inselected hindlimb muscles and the diaphragm of Syrian Golden hamsters 6 mo after intratracheal instillation of either saline (Con,n = 7) or elastase [emphysema(Emp); 25 units/100 g body weight, n = 8]. Activity level was monitored, and no difference betweengroups was found. Excised lung volume increased with emphysema (Con,1.5 ± 0.3 g; Emp, 3.0 ± 0.3 g,P < 0.002). Emphysema significantly reduced CS activity in the gastrocnemius (Con, 45.1 ± 2.0; Emp, 39.2 ± 0.8 µmol · min¹ · gwet wt¹,P < 0.05) and vastus lateralis (Con,48.5 ± 1.5; Emp, 44.9 ± 0.8 µmol · min¹ · gwet wt¹,P < 0.05) but not in the plantaris(Con, 47.4 ± 3.9; Emp, 48.0 ± 2.1 µmol · min¹ · gwet wt¹,P < 0.05) muscle. In contrast, CSactivity increased in the costal (Con, 61.1 ± 1.8; Emp, 65.1 ± 1.5 µmol · min¹ · gwet wt¹,P < 0.05) and crural (Con, 58.5 ± 2.0; Emp, 65.7 ± 2.2 µmol · min¹ · gwet wt¹, P < 0.05) regions of the diaphragm. These data indicate that emphysema perse can induce decrements in the oxidative capacity of certainnonventilatory skeletal muscles that may contribute to exerciselimitations in the emphysematous patient.