Effects of N2O narcosis on breathing and effort sensations during exercise and inspiratory resistive loading

Fothergill, D. M., and N. A. Carlson. Effects ofN₂O narcosis on breathing andeffort sensations during exercise and inspiratory resistive loading.J. Appl. Physiol. 81(4):1562-1571, 1996.The influence of nitrous oxide(N₂O) narcosis on the responses toexercise and inspiratory resistive loading was studied in thirteen maleUS Navy divers. Each diver performed an incremental bicycle exercisetest at 1 ATA to volitional exhaustion while breathing a 23%N₂O gas mixture and a nonnarcoticgas of the same PO₂, density, andviscosity. The same gas mixtures were used during four subsequent30-min steady-state submaximal exercise trials in which the subjectsbreathed the mixtures both with and without an inspiratory resistance(5.5 vs. 1.1 cmH₂O ^· s ^· l¹at 1 l/s). Throughout each test, subjective ratings of respiratory effort (RE), leg exertion, and narcosis were obtained with acategory-ratio scale. The level of narcosis was rated between slightand moderate for the N₂O mixturebut showed great individual variation. Perceived leg exertion and thetime to exhaustion were not significantly different with the twobreathing mixtures. Heart rate was unaffected by the gas mixture andinspiratory resistance at rest and during steady-state exercise but wassignificantly lower with the N₂O mixture during incremental exercise (P < 0.05). Despite significant increases in inspiratory occlusionpressure (13%; P < 0.05),esophageal pressure (12%; P < 0.001), expired minute ventilation (4%;P < 0.01), and the work rate ofbreathing (15%; P < 0.001) when the subjects breathed the N₂O mixture,RE during both steady-state and incremental exercise was 25% lowerwith the narcotic gas than with the nonnarcotic mixture(P < 0.05). We conclude that the narcotic-mediated changes in ventilation, heart rate, and RE induced by23% N₂O are not of sufficientmagnitude to influence exercise tolerance at surface pressure.Furthermore, the load-compensating respiratory reflexes responsible formaintaining ventilation during resistive breathing are not depressed byN₂O narcosis.

     

Acid-base regulation after maximal exercise testing in late gestation

Kemp, Justin G., Felicia A. Greer, and Larry A. Wolfe.Acid-base regulation after maximal exercise testing in late gestation. J. Appl. Physiol. 83(2):644-651, 1997.This study employed Stewart's physicochemicalapproach to quantify the effects of pregnancy and strenuous exercise onthe independent determinants of plasmaH⁺ concentration([H⁺]). Subjects werenine physically active pregnant women [mean gestational age = 33 ± 1 (SE) wk] and 14 age-matched nonpregnant controls. Venousblood samples and respiratory data were obtained at rest and during 15 min of recovery from a maximal cycle ergometer test that involved 20 W/min increases in work rate to exhaustion. Mean values for[H⁺],PCO₂, and total protein increased,whereas those for bicarbonate concentration([HCO₃]) and the strong ion difference ([SID]) decreased in the transition fromrest to maximal exercise within both groups. At rest and throughoutpostexercise recovery, the pregnant group exhibited significantly lowermean values for PCO₂,[HCO₃], and total protein,whereas [SID] was significantly lower at rest and early recovery from exercise.[H⁺] was also lower atall sampling times in the pregnant group, but this effect wassignificant only at rest. Our results support the hypothesis thatreduced PCO₂ and weak acidconcentration are important mechanisms to regulate plasma[H⁺] and to maintain aless acidic plasma environment at rest and after exercise in lategestation compared with the nonpregnant state. These effects areestablished in the resting state and appear to be maintained aftermaximal exertion.

     

Peripheral circulatory factors limit rate of increase in muscle O2 uptake at onset of heavy exercise

We used anexercise paradigm with repeated bouts of heavy forearm exercise to testthe hypothesis that alterations in local acid-base environment thatremain after the first exercise result in greater blood flow andO₂ delivery at the onset of the second bout of exercise.Two bouts of handgrip exercise at 75% peak workload were performed for5 min, separated by 5 min of recovery. We continuously measured bloodflow using Doppler ultrasound and sampled venous blood forO₂ content, PCO₂, pH, and lactateand potassium concentrations, and we calculated muscle O₂uptake (O₂). Forearm blood flow waselevated before the second exercise compared with the first andremained higher during the first 30 s of exercise (234 ± 18 vs. 187 ± 4 ml/min, P < 0.05). Flow was notdifferent at 5 min. Arteriovenous O₂ content difference waslower before the second bout (4.6 ± 0.9 vs. 7.2 ± 0.7 mlO₂/dl) and higher by 30 s of exercise(11.2 ± 0.7 vs. 10.8 ± 0.7 ml O₂/dl,P < 0.05). Muscle O₂was unchanged before the start of exercise but was elevated during thefirst 30 s of the transition to the second exercise bout(26.0 ± 2.1 vs. 20.0 ± 0.9 ml/min, P < 0.05). Changes in venous blood PCO₂, pH, andlactate concentration were consistent with reduced reliance onanaerobic glycolysis at the onset of the second exercise bout. Thesedata show that limitations of muscle blood flow can restrict theadaptation of oxidative metabolism at the onset of heavy muscular exertion.

     

Furosemide reduces accumulated oxygen deficit in horses during brief intense exertion

Hinchcliff, K. W., K. H. McKeever, W. W. Muir, and R. A. Sams. Furosemide reduces accumulated oxygen deficit inhorses during brief intense exertion. J. Appl.Physiol. 81(4): 1550-1554, 1996.We theorizedthat furosemide-induced weight reduction would reduce the contributionof anaerobic metabolism to energy expenditure of horses during intenseexertion. The effects of furosemide on accumulatedO₂ deficit and plasma lactateconcentration of horses during high-intensity exercise were examined ina three-way balance randomized crossover study. Nine horses completedeach of three trials: 1) a control(C) trial, 2) a furosemide-unloaded(FU) trial in which the horse received furosemide 4 h before running, and 3) a furosemide weight-loaded(FL) trial during which the horse received furosemide and carriedweight equal to the weight lost after furosemide administration. Horsesran for 2 min at ~120% maximalO₂ consumption. Furosemide (FU)increased O₂ consumption (ml ^· 2 min^{1 ·} kg¹)compared with C (268 ± 9 and 257 ± 9, P < 0.05), whereas FL was notdifferent from C (252 ± 8). AccumulatedO₂ deficit (ml O₂ equivalents/kg) wassignificantly (P < 0.05) lowerduring FU (81.2 ± 12.5), but not during FL (96.9 ± 12.4), thanduring C (91.4 ± 11.5). Rate of increase in blood lactateconcentration (mmol ^· 2 min^{1 ·} kg¹)after FU (0.058 ± 0.001), but not after FL (0.061 ± 0.001), was significantly (P < 0.05) lower than after C (0.061 ± 0.001). Furosemide decreased theaccumulated O₂ deficit and rate ofincrease in blood lactate concentration of horses during briefhigh-intensity exertion. The reduction in accumulatedO₂ deficit in FU-treated horseswas attributable to an increase in the mass-specific rate ofO₂ consumption during thehigh-intensity exercise test.

     

Interaction of leg stiffness and surface stiffness during human hopping

Ferris, Daniel P., and Claire T. Farley. Interaction ofleg stiffness and surface stiffness during human hopping.J. Appl.Physiol. 82(1): 15-22, 1997.When mammals run,the overall musculoskeletal system behaves as a single linear "legspring." We used force platform and kinematic measurements todetermine whether leg spring stiffness(k_leg) isadjusted to accommodate changes in surface stiffness(k_surf) whenhumans hop in place, a good experimental model for examiningadjustments tok_leg in bouncinggaits. We found thatk_leg was greatlyincreased to accommodate surfaces of lower stiffnesses. The seriescombination ofk_leg andk_surf[total stiffness(k_tot)]was independent ofk_surf at a givenhopping frequency. For example, when humans hopped at a frequency of 2 Hz, they tripled theirk_leg on the leaststiff surface(k_surf = 26.1 kN/m; k_leg = 53.3 kN/m) compared with the most stiff surface(k_surf = 35,000 kN/m; k_leg = 17.8 kN/m). Values fork_tot were notsignificantly different on the least stiff surface (16.7 kN/m) and themost stiff surface (17.8 kN/m). Because of thek_leg adjustment,many aspects of the hopping mechanics (e.g., ground-contact time andcenter of mass vertical displacement) remained remarkably similardespite a >1,000-fold change ink_surf. This studyprovides insight into howk_leg adjustmentscan allow similar locomotion mechanics on the variety of terrainsencountered by runners in the natural world.

     

Effects of training and a single session of exercise on lipids and apolipoproteins in hypercholesterolemic men

Crouse, Stephen F., Barbara C. O'Brien, Peter W. Grandjean,Robert C. Lowe, J. James Rohack, and John S. Green. Effects oftraining and a single session of exercise on lipids and apolipoproteins in hypercholesterolemic men. J. Appl.Physiol. 83(6): 2019-2028, 1997.To differentiatebetween transient (acute) and training (chronic) effects of exercise attwo different intensities on blood lipids and apolipoproteins (apo), 26 hypercholesterolemic men (cholesterol = 258 mg/dl, age = 47 yr, weight = 81.9 kg) trained three times per week for 24 wk, 350 kcal/session athigh (80% maximal O₂ uptake,n = 12) or moderate (50% maximalO₂ uptake, n = 14) intensity. Serum lipid andapolipoprotein (apo) concentrations (plasma volume adjusted) weremeasured before and immediately, 24, and 48 h after exercise on fourdifferent occasions corresponding to 0, 8, 16, and 24 wk of training.Data were analyzed using three-way repeated-measures multivariateanalysis of variance followed by analysis of variance and Duncan'sprocedures ( = 0.05). A transient 6% rise inlow-density-lipoprotein cholesterol measured before training at the24-h time point was no longer evident after training. Triglyceridesfell and total cholesterol, high-density-lipoprotein cholesterol(HDL-C), HDL₃-C, apo A-I, and apoB rose 24-48 h after exercise regardless of training or intensity.Total cholesterol, HDL₃-C, apoA-I, and apo B were lower andHDL₂-C was higher after trainingthan before training. Thus exercise training and a single session ofexercise exert distinct and interactive effects on lipids andapolipoproteins. These results support the practice of training atleast every other day to obtain optimal exercise benefits.

     

Reduced oxidation rates of ingested glucose during prolonged exercise with low endogenous CHO availability

Jeukendrup, Asker E., Lars B. Borghouts, Wim H. M. Saris,and Anton J. M. Wagenmakers. Reduced oxidation rates of ingested glucose during prolonged exercise with low endogenous CHO availability. J. Appl. Physiol. 81(5):1952-1957, 1996.This study investigated the effect of endogenouscarbohydrate (CHO) availability on oxidation rates of ingested glucoseduring moderate-intensity exercise. Seven well-trained cyclistsperformed two trials of 120 min of cycling exercise in random order at57% maximal O₂ consumption. Preexercise glycogen concentrations were manipulated byglycogen-lowering exercise in combination with CHO restriction[low-glycogen (LG) trial] or CHO loading[moderate-to-high-glycogen (HG) trial]. In the LG and HGtrials, subjects ingested 4 ml/kg body wt of an 8% corn-derivedglucose solution of high natural¹³C abundance at the start,followed by boluses of 2 ml/kg every 15 min. The third trial, in whichpotato-derived glucose was ingested, served as a control test forbackground correction. Exogenous glucose oxidation rates werecalculated from the ¹³C enrichmentof the ingested glucose and of the breathCO₂. Total CHO oxidation was lowerin the LG trial than in the HG trial during 60-120 min of exercise[84 ± 7 (SE) vs. 116 ± 8 g;P < 0.05]. Exogenous CHOoxidation in this period was 28% lower in the LG trial compared withthe HG trial. Maximal exogenous oxidation rates were also lower(P < 0.05) in the LG trial (0.64 ± 0.05 g/min) than in the HG trial (0.88 ± 0.04 g/min). Thisdecreased utilization of exogenous glucose was accompanied by increased plasma free fatty acid levels (2-3 times higher) and lower insulin concentrations. It is concluded that glycogen-lowering exercise, performed the evening before an exercise bout, in combination with CHOrestriction leads to a reduction of the oxidation rate of ingestedglucose during moderate-intensity exercise.

     

Hormonal and metabolic responses to exercise across time of day and menstrual cycle phase

Galliven, E. A., A. Singh, D. Michelson, S. Bina, P. W. Gold, and P. A. Deuster. Hormonal and metabolic responses to exercise across time of day and menstrual cycle phase.J. Appl. Physiol. 83(6):1822-1831, 1997.Two studies, each utilizing short-term treadmillexercise of a different intensity, assessed the metabolic and hormonalresponses of women to exercise in the morning (AM) and late afternoon(PM). In study 1, plasmaconcentrations of growth hormone, arginine vasopressin, catecholamines,adrenocorticotropic hormone, cortisol, lactate, and glucose weremeasured before, during, and after high-intensity exercise (90%maximal O₂ uptake) in the AM andPM. In study 2, plasma concentrationsof adrenocorticotropic hormone, cortisol, lactate, andglucose were measured before, during, and aftermoderate-intensity exercise (70% maximalO₂ uptake) in the AM and PM in thefollicular (days 3-9), midcycle (days 10-16), and luteal(days 18-26) phases of themenstrual cycle. The results of studies1 and 2 revealed nosignificant diurnal differences in the magnitude of responses for anymeasured variable. In addition, study2 revealed a significant time-by-phase interaction forglucose (P = 0.014). However, netintegrated responses were similar across cycle phases. These datasuggest that metabolic and hormonal responses to short-term,high-intensity exercise can be assessed with equal reliability in theAM and PM and that there are subtle differences in blood glucoseresponses to moderate-intensity exercise across menstrual cycle phase.

     

Influence of pregnancy on the febrile response to ICV administration of PGE1 in rats studied in a thermocline

Eliason, Heather L., and James E. Fewell. Influence ofpregnancy on the febrile response to ICV administration ofPGE₁ in rats studied in athermocline. J. Appl. Physiol. 82(5):1453-1458, 1997.Rats near term of pregnancy have an attenuatedfebrile response to intracerebroventricular (ICV) injection ofprostaglandin E₁ (PGE₁) when they are studied atan ambient temperature below their thermoneutral zone. Given thatnonshivering thermogenesis in brown adipose tissue is impaired inrodents near term of pregnancy, it is possible that the attenuatedfebrile response is forced by impairment of this component of theautonomic thermoregulatory response. If this were the case, thennear-term pregnant rats should develop a "normal" fever afterPGE₁ administration if they werestudied in a thermocline where they could utilize behavioral as well asautonomic thermoregulatory effectors to increase their body coretemperature (T_bc). Experimentswere, therefore, carried out on 13 nonpregnant and 14 pregnantchronically instrumented rats in a thermocline (temperature gradient10-40°C) to investigate theirT_bc responses to ICV injection ofPGE₁. ICV injection of 0.2 µgPGE₁ produced significantincreases in T_bc and fever index in both nonpregnant and pregnant animals (day19 of gestation); the increases, however, weresignificantly attenuated in the pregnant compared with the nonpregnantrats. Behavioral (e.g., selected ambient temperature) and autonomic(e.g., oxygen consumption) thermoregulatory effectors were activated toincrease T_bc after ICVPGE₁ in both groups of animals,but the duration of activation was shortened in pregnant compared withnonpregnant rats. The abbreviated thermoregulatory effector responsesand the resulting attenuated febrile response toPGE₁ in the pregnant rats may have resulted from a pregnancy-related activation of an endogenous antipyretic system.

     

Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women

Brooks, E. M., A. L. Morgan, J. M. Pierzga, S. L. Wladkowski, J. T. O'Gorman, J. A. Derr, and W. L. Kenney. Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women. J. Appl.Physiol. 83(2): 477-484, 1997.This investigationexamined effects of chronic (2 yr) hormone replacement therapy (HRT),both estrogen replacement therapy (ERT) and estrogen plus progesteronetherapy (E+P), on core temperature and skin blood flow responses ofpostmenopausal women. Twenty-five postmenopausal women [9 not onHRT (NO), 8 on ERT, 8 on E+P] exercised on a cycle ergometer for1 h at an ambient temperature of 36°C. Cutaneous vascularconductance (CVC) was monitored by laser-Doppler flowmetry, and forearmvascular conductance (FVC) was measured by using venous occlusionplethysmography. Iontophoresis of bretylium tosylate was performedbefore exercise to block local vasoconstrictor (VC) activity at oneskin site on the forearm. Rectal temperature (T_re) was ~0.5°C lower forthe ERT group (P < 0.01) comparedwith E+P and NO groups at rest and throughout exercise. FVC: mean body temperature (T_b) and CVC:T_b curves were shifted~0.5°C leftward for the ERT group(P < 0.0001). Baseline CVC wassignificantly higher in the ERT group(P < 0.05), but there was nointeraction between bretylium treatment and groups once exercise wasinitiated. These results suggest that1) chronic ERT likely acts centrally to decrease T_re,2) ERT lowers theT_re at which heat-loss effector mechanisms are initiated, primarily by actions on active cutaneous vasodilation, and 3) addition ofexogenous progestins in HRT effectively blocks these effects.

     

Skeletal muscle chemoreflex and pHi in exercise ventilatory control

Oelberg, David A., Allison B. Evans, Mirko I. Hrovat, PaulP. Pappagianopoulos, Samuel Patz, and David M. Systrom. Skeletal muscle chemoreflex and pH_i inexercise ventilatory control. J. Appl.Physiol. 84(2): 676-682, 1998.To determinewhether skeletal muscle hydrogen ion mediates ventilatory drive inhumans during exercise, 12 healthy subjects performed three bouts ofisotonic submaximal quadriceps exercise on each of 2 days in a 1.5-Tmagnet for ³¹P-magnetic resonancespectroscopy(³¹P-MRS). Bilaterallower extremity positive pressure cuffs were inflated to 45 Torr duringexercise (BLPP_ex) or recovery(BLPP_rec) in a randomized orderto accentuate a muscle chemoreflex. Simultaneous measurements were madeof breath-by-breath expired gases and minute ventilation, arterializedvenous blood, and by ³¹P-MRS ofthe vastus medialis, acquired from the average of 12 radio-frequencypulses at a repetition time of 2.5 s. WithBLPP_ex, end-exercise minuteventilation was higher (53.3 ± 3.8 vs. 37.3 ± 2.2 l/min;P < 0.0001), arterializedPCO₂ lower (33 ± 1 vs. 36 ± 1 Torr; P = 0.0009), and quadricepsintracellular pH (pH_i) more acid (6.44 ± 0.07 vs. 6.62 ± 0.07; P = 0.004), compared withBLPP_rec. Bloodlactate was modestly increased withBLPP_ex but without a change inarterialized pH. For each subject, pH_i was linearly relatedto minute ventilation during exercise but not to arterialized pH. Thesedata suggest that skeletal muscle hydrogen ion contributes to theexercise ventilatory response.

     

Effect of prior O2 breathing on ventilatory response to sustained isocapnic hypoxia in adult humans

Honda, Y., H. Tani, A. Masuda, T. Kobayashi, T. Nishino, H. Kimura, S. Masuyama, and T. Kuriyama. Effect of priorO₂ breathing on ventilatoryresponse to sustained isocapnic hypoxia in adult humans.J. Appl. Physiol. 81(4):1627-1632, 1996.Sixteen healthy volunteers breathed 100%O₂ or room air for 10 min in random order, then their ventilatory response to sustained normocapnic hypoxia (80% arterial O₂saturation, as measured with a pulse oximeter) was studied for 20 min.In addition, to detect agents possibly responsible for the respiratorychanges, blood plasma of 10 of the 16 subjects was chemically analyzed.1) Preliminary O₂ breathing uniformly andsubstantially augmented hypoxic ventilatory responses.2) However, the profile ofventilatory response in terms of relative magnitude, i.e., biphasichypoxic ventilatory depression, remained nearly unchanged.3) Augmented ventilatory incrementby prior O₂ breathing wassignificantly correlated with increment in the plasma glutamine level.We conclude that preliminary O₂administration enhances hypoxic ventilatory response without affectingthe biphasic response pattern and speculate that the excitatory aminoacid neurotransmitter glutamate, possibly derived from augmentedglutamine, may, at least in part, play a role in this ventilatoryenhancement.

     

A moderate glycemic meal before endurance exercise can enhance performance

Kirwan, John P., Donal O'Gorman, and William J. Evans.A moderate glycemic meal before endurance exercise can enhance performance. J. Appl. Physiol. 84(1):53-59, 1998.The purpose of this study was to determine whetherpresweetened breakfast cereals with various fiber contents and amoderate glycemic index optimize glucose availability and improveendurance exercise performance. Six recreationally active women ate 75 g of available carbohydrate in the form of breakfast cereals: sweetenedwhole-grain rolled oats (SRO, 7 g of dietary fiber) or sweetenedwhole-oat flour (SOF, 3 g of dietary fiber) and 300 ml of water orwater alone (Con). The meals were provided 45 min before semirecumbentcycle ergometer exercise to exhaustion at 60% of peakO₂ consumption (O_{2 peak}). Diet andphysical activity were controlled by having the subjects reside in theGeneral Clinical Research Center for 2 days before each trial. Bloodsamples were drawn from an antecubital vein for glucose, free fattyacid (FFA), glycerol, insulin, epinephrine, and norepinephrinedetermination. Breath samples were obtained at 15-min intervals aftermeal ingestion and at 30-min intervals during exercise. Muscle glycogenconcentration was determined from biopsies taken from the vastuslateralis muscle before the meal and immediately after exercise. PlasmaFFA concentrations were lower (P < 0.05) during the SRO and SOF trials for the first 60 and 90 min ofexercise, respectively, than during the Con trial. Respiratory exchangeratios were higher (P < 0.05) at 90 and 120 min of exercise for the SRO and SOF trials, respectively, than for the Con trial. At exhaustion, glucose, insulin, FFA, glycerol, epinephrine, and norepinephrine concentrations, respiratory exchange ratio, and muscle glycogen use in the vastus lateralis muscle weresimilar for all trials. Exercise time to exhaustion was 16% longer(P < 0.05) during the SRO thanduring the Con trial: 266.5 ± 13 and 225.1 ± 8 min,respectively. There was no difference in exercise time for the SOF(250.8 ± 12) and Con trials. We conclude that eating ameal with a high dietary fiber content and moderate glycemic index 45 min before prolonged moderately intense exercise significantly enhancesexercise capacity.

     

Ventilatory response to exercise in subjects breathing CO2 or HeO2

Babb, T. G. Ventilatory response to exercise insubjects breathing CO₂ orHeO₂.J. Appl. Physiol. 82(3): 746-754, 1997.To investigate the effects of mechanical ventilatory limitationon the ventilatory response to exercise, eight older subjects with normal lung function were studied. Each subject performed graded cycleergometry to exhaustion once while breathing room air; once whilebreathing 3% CO₂-21%O₂-balanceN₂; and once while breathing HeO₂ (79% He and 21%O₂). Minute ventilation(E) and respiratory mechanics weremeasured continuously during each 1-min increment in work rate (10 or20 W). Data were analyzed at rest, at ventilatory threshold (VTh),and at maximal exercise. When the subjects were breathing 3%CO₂, there was an increase(P < 0.001) inE at rest and at VTh but not duringmaximal exercise. When the subjects were breathingHeO₂,E was increased(P < 0.05) only during maximalexercise (24 ± 11%). The ventilatory response to exercise belowVTh was greater only when the subjects were breathing 3% CO₂(P < 0.05). Above VTh, theventilatory response when the subjects were breathingHeO₂ was greater than whenbreathing 3% CO₂(P < 0.01). Flow limitation, aspercent of tidal volume, during maximal exercise was greater(P < 0.01) when the subjects werebreathing CO₂ (22 ± 12%) thanwhen breathing room air (12 ± 9%) or when breathingHeO₂ (10 ± 7%)(n = 7). End-expiratory lung volumeduring maximal exercise was lower when the subjects were breathingHeO₂ than when breathing room airor when breathing CO₂(P < 0.01). These data indicate thatolder subjects have little reserve for accommodating an increase inventilatory demand and suggest that mechanical ventilatory constraintsinfluence both the magnitude of Eduring maximal exercise and the regulation ofE and respiratory mechanics duringheavy-to-maximal exercise.

     

Prostaglandin production contributes to exercise-induced vasodilation in heart failure

Lang, Chim C., Don B. Chomsky, Javed Butler, Shiv Kapoor,and John R. Wilson. Prostaglandin production contributes toexercise-induced vasodilation in heart failure. J. Appl. Physiol. 83(6): 1933-1940, 1997.Endothelial release of prostaglandins may contribute toexercise-induced skeletal muscle arteriolar vasodilation in patientswith heart failure. To test this hypothesis, we examined the effect ofindomethacin on leg circulation and metabolism in eight chronic heartfailure patients, aged 55 ± 4 yr. Central hemodynamics and legblood flow, determined by thermodilution, and leg metabolic parameterswere measured during maximum treadmill exercise before and 2 h afteroral administration of indomethacin (75 mg). Leg release of6-ketoprostaglandin F₁ was alsomeasured. During control exercise, leg blood flow increased from 0.34 ± 0.03 to 1.99 ± 0.19 l/min(P < 0.001), legO₂ consumption from 13.6 ± 1.8 to 164.5 ± 16.2 ml/min (P < 0.001), and leg prostanoid release from 54.1 ± 8.5 to267.4 ± 35.8 pg/min (P < 0.001).Indomethacin suppressed release of prostaglandinF₁(P < 0.001) throughout exercise anddecreased leg blood flow during exercise(P < 0.05). This was associated witha corresponding decrease in leg O₂ consumption (P < 0.05) and a higher level offemoral venous lactate at peak exercise(P < 0.01). These data suggest thatrelease of vasodilatory prostaglandins contributes to skeletal musclearteriolar vasodilation in patients with heart failure.

     

Mechanical behavior of skeletal muscle during intermittent voluntary isometric contractions in humans

Vøllestad, N. K., I. Sejersted, and E. Saugen. Mechanical behavior of skeletal muscle duringintermittent voluntary isometric contractions in humans.J. Appl. Physiol. 83(5):1557-1565, 1997.Changes in contractile speed and force-fusionproperties were examined during repetitive isometric contractions withthe knee extensors at three different target force levels. Sevenhealthy subjects were studied at target force levels of 30, 45, and60% of their maximal voluntary contraction (MVC) force. Repeated 6-s contractions followed by 4-s rest were continued until exhaustion. Contractile speed was determined for contractions elicited by electrical stimulation at 1-50 Hz given during exercise and a subsequent 27-min recovery period. Contraction time remained unchanged during exercise and recovery, except for an initial rapid shift in thetwitch properties. Half relaxation time(RT_1/2) decreased gradually by 20-40% during exercise at 30 and 45% of MVC. In the recovery period, RT_1/2 values werenot fully restored to preexercise levels. During exercise at 60% MVC,the RT_1/2 decreased for twitches and increased for the 50-Hz stimulation. In the recovery period after60% MVC, RT_1/2 values declinedtoward those seen after the 30 and 45% MVC exercise. The forceoscillation amplitude in unfused tetani relative to the mean forceincreased during exercise at 30 and 45% MVC but remained unalteredduring the 60% MVC exercise. This altered force-fusion was closelyassociated with the changes inRT_1/2. The faster relaxation mayat least partly explain the increased energy cost of contractionreported previously for the same type of exercise.

     

Skeletal muscle ECF pH error signal for exercise ventilatory control

Evans, Allison B., Larry W. Tsai, David A. Oelberg, HomayounKazemi, and David M. Systrom. Skeletal muscle ECF pH error signalfor exercise ventilatory control. J. Appl.Physiol. 84(1): 90-96, 1998.An autonomic reflexlinking exercising skeletal muscle metabolism to central ventilatorycontrol is thought to be mediated by neural afferents having freeendings that terminate in the interstitial fluid of muscle. Todetermine whether changes in muscle extracellular fluid pH(pH_e) can provide an errorsignal for exercise ventilatory control,pH_e was measured duringelectrically induced contraction by³¹P-magnetic resonancespectroscopy and the chemical shift of a phosphorylated, pH-sensitivemarker that distributes to the extracellular fluid (phenylphosphonicacid). Seven lightly anesthetized rats underwentunilateral continuous 5-Hz sciatic nerve stimulation in an 8.45-Tnuclear magnetic resonance magnet, which resulted in a mixed lacticacidosis and respiratory alkalosis, with no net change in arterial pH.Skeletal muscle intracellular pH fell from 7.30 ± 0.03 units atrest to 6.72 ± 0.05 units at 2.4 min of stimulation and then roseto 7.05 ± 0.01 units (P < 0.05), despite ongoing stimulation and muscle contraction.Despite arterial hypocapnia, pH_eshowed an immediate drop from its resting baseline of 7.40 ± 0.01 to 7.16 ± 0.04 units (P < 0.05)and remained acidic throughout the stimulation protocol. During the on-and off-transients for 5-Hz stimulation, changes in the pH gradientbetween intracellular and extracellular compartments suggestedtime-dependent recruitment of sarcolemmal ion-transport mechanisms.pH_e of exercising skeletal musclemeets temporal and qualitative criteria necessary for a ventilatorymetaboreflex mediator in a setting where arterial pH doesnot.

     

Breathing of awake goats during prolonged dysfunction of caudal M ventrolateral medullary neurons

Forster, H. V., L. G. Pan, T. F. Lowry, T. Feroah, W. M. Gershan, A. A. Whaley, M. M. Forster, and B. Sprtel. Breathing ofawake goats during prolonged dysfunction of caudal M ventrolateral medullary neurons. J. Appl. Physiol.84(1): 129-140, 1998.Cooling the caudal M ventrolateralmedullary (VLM) surface for 30 s results in a sustained apnea inanesthetized goats but only a 30% decrease in breathing in awakegoats. The purpose of the present study was to determine, in the awakestate, the effect of prolonged (minutes, hours) caudal M neuronaldysfunction on eupneic breathing andCO₂ sensitivity. Dysfunction wascreated by ejecting excitatory amino acid receptor antagonists or aneurotoxin on the VLM surface through guide tubes chronically implantedbilaterally on a 10- to 12-mm²portion of the caudal M VLM surface of 12 goats. Unilateral and bilateral ejections (1 µl) of selective antagonists forN-methyl-D-aspartic acid ornon-N-methyl-D-asparticacid receptors had no significant effect on eupneic breathing orCO₂ sensitivity. Unilateralejection of a nonselective excitatory amino acid receptor antagonistgenerally had no effect on eupneic breathing orCO₂ sensitivity. However, bilateral ejection of this antagonist resulted in a significant 2-Torrhypoventilation during eupnea and a significant reduction inCO₂ sensitivity to 60 ± 9% ofcontrol. Unilateral ejection of the neurotoxin kainic acid initiallystimulated breathing; however, breathing then returned to near controlwith no incidence of apnea. After the kainic acid ejection,CO₂ sensitivity was reducedsignificantly to 60 ± 7% of control. We conclude that in the awakestate a prolonged dysfunction of caudal M VLM neurons results incompensation by other mechanisms (e.g., carotid chemoreceptors, wakefulness) to maintain near-normal eupneic breathing, butcompensation is more limited for maintainingCO₂ sensitivity.

     

Effect of ingested sodium bicarbonate on muscle force, fatigue, and recovery

Verbitsky, O., J. Mizrahi, M. Levin, and E. Isakov.Effect of ingested sodium bicarbonate on muscle force, fatigue, and recovery. J. Appl. Physiol. 83(2):333-337, 1997.The influence of acute ingestion ofNaHCO₃ on fatigue and recovery ofthe quadriceps femoris muscle after exercise was studied in six healthymale subjects. A bicycle ergometer was used for exercising under three loading conditions: test A, loadcorresponding to maximal oxygen consumption; testB, load in test A + 17%; test C, load intest B but performed 1 h after acuteingestion of NaHCO₃.Functional electrical stimulation (FES) was applied to provokeisometric contraction of the quadriceps femoris. The resulting kneetorque was monitored during fatigue (2-min chronic FES) and recovery (10-s FES every 10 min, for 40 min). Quadriceps torques were higher inthe presence of NaHCO₃(P < 0.05): withNaHCO₃ the peak, residual, andrecovery (after 40 min) normalized torques were, respectively, 0.68 ± 0.05 (SD), 0.58 ± 0.05, and 0.73 ± 0.05; withoutNaHCO₃ the values were 0.45 ± 0.04, 0.30 ± 0.06, and 0.63 ± 0.06. The increasedtorques obtained after acute ingestion ofNaHCO₃ indicate the possibleexistence of improved nonoxidative glycolysis in isometric contraction,resulting in reduced fatigue and enhanced recovery.

     

Ventilatory response to helium-oxygen breathing during exercise: effect of airway anesthesia

Krishnan, Bharath S., Ron E. Clemens, Trevor A. Zintel,Martin J. Stockwell, and Charles G. Gallagher. Ventilatory response to helium-oxygen breathing during exercise: effect of airwayanesthesia. J. Appl. Physiol. 83(1):82-88, 1997.The substitution of a normoxic helium mixture(HeO₂) for room air (Air) during exercise results in a sustained hyperventilation, which is present evenin the first breath. We hypothesized that this response is dependent onintact airway afferents; if so, airway anesthesia (Anesthesia) shouldaffect this response. Anesthesia was administered to the upper airwaysby topical application and to lower central airways by aerosolinhalation and was confirmed to be effective for over 15 min. Subjectsperformed constant work-rate exercise (CWE) at 69 ± 2 (SE) % maximal work rate on a cycle ergometer on three separate days: twiceafter saline inhalation (days 1 and3) and once after Anesthesia(day 2). CWE commenced after a briefwarm-up, with subjects breathing Air for the first 5 min (Air-1),HeO₂ for the next 3 min, and Airagain until the end of CWE (Air-2). The resistance of the breathingcircuit was matched for Air andHeO₂. BreathingHeO₂ resulted in a small butsignificant increase in minute ventilation(I) anddecrease in alveolar PCO₂ in both theSaline (average of 2 saline tests; not significant) and Anesthesiatests. Although Anesthesia had no effect on the sustainedhyperventilatory response to HeO₂breathing, theI transientswithin the first six breaths ofHeO₂ were significantly attenuatedwith Anesthesia. We conclude that theI response to HeO₂ is not simply due to areduction in external tubing resistance and that, in humans, airwayafferents mediate the transient but not the sustained hyperventilatoryresponse to HeO₂ breathing duringexercise.