Training-induced alterations of carbohydrate metabolism in women: women respond differently from men

We examined the hypothesis that glucose flux wasdirectly related to relative exercise intensity both beforeand after a 12-wk cycle ergometer training program [5days/wk, 1-h duration, 75% peakO₂ consumption(O_{2 peak})] inhealthy female subjects (n = 17; age23.8 ± 2.0 yr). Two pretraining trials (45 and 65% of O_{2 peak})and two posttraining trials [same absolute workload (65% of oldO_{2 peak})and same relative workload (65% of new O_{2 peak})] wereperformed on nine subjects by using a primed-continuous infusion of[1-¹³C]- and[6,6-²H]glucose.Eight additional subjects were studied by using[6,6-²H]glucose.Subjects were studied postabsorption for 90 min of rest and 1 h ofcycling exercise. After training, subjects increased O_{2 peak} by 25.2 ± 2.4%. Pretraining, the intensity effect on glucose kinetics wasevident between 45 and 65% ofO_{2 peak} with rates ofappearance (R_a: 4.52 ± 0.25 vs. 5.53 ± 0.33 mg · kg¹ · min¹),disappearance (R_d: 4.46 ± 0.25 vs. 5.54 ± 0.33 mg · kg¹ · min¹),and oxidation (R_ox: 2.45 ± 0.16 vs. 4.35 ± 0.26 mg · kg¹ · min¹)of glucose being significantly greater(P  0.05) in the 65% thanin the 45% trial. Training reducedR_a (4.7 ± 0.30 mg · kg¹ · min¹),R_d (4.69 ± 0.20 mg · kg¹ · min¹),and R_ox (3.54 ± 0.50 mg · kg¹ · min¹)at the same absolute workload (P  0.05). When subjects were tested at the same relative workload,R_a,R_d, andR_ox were not significantlydifferent after training. However, at both workloads after training,there was a significant decrease in total carbohydrate oxidation asdetermined by the respiratory exchange ratio. These results show thefollowing in young women: 1)glucose use is directly related to exercise intensity;2) training decreasesglucose flux for a given power output;3) when expressed asrelative exercise intensity, training does not affect the magnitude ofblood glucose flux during exercise; but4) training does reduce totalcarbohydrate oxidation.

     

Training-induced alterations of glucose flux in men

Friedlander, Anne L., Gretchen A. Casazza, Michael A. Horning, Melvin J. Huie, and George A. Brooks. Training-induced alterations of glucose flux in men. J. Appl.Physiol. 82(4): 1360-1369, 1997.We examined thehypothesis that glucose flux was directly related to relative exerciseintensity both before and after a 10-wk cycle ergometer trainingprogram in 19 healthy male subjects. Two pretraining trials [45and 65% of peak O₂ consumption(O_{2 peak})] andtwo posttraining trials (same absolute and relative intensities as 65%pretraining) were performed for 90 min of rest and 1 h of cyclingexercise. After training, subjects increasedO_{2 peak} by9.4 ± 1.4%. Pretraining, the intensity effect on glucose kinetics was evident with rates of appearance(R_a; 5.84 ± 0.23 vs. 4.73 ± 0.19 mg · kg¹ · min¹),disappearance (R_d; 5.78 ± 0.19 vs. 4.73 ± 0.19 mg · kg¹ · min¹),oxidation (R_ox; 5.36 ± 0.15 vs. 3.41 ± 0.23 mg · kg¹ · min¹),and metabolic clearance (7.03 ± 0.56 vs. 5.20 ± 0.28 ml · kg¹ · min¹)of glucose being significantly greater(P  0.05) in the 65% than the 45%O_{2 peak} trial. WhenR_d was expressed as a percentage of total energy expended per minute(R_{d E}), there was nodifference between the 45 and 65% intensities. Training did reduceR_a (4.63 ± 0.25),R_d (4.65 ± 0.24),R_ox (3.77 ± 0.43), andR_{d E} (15.30 ± 0.40 to12.85 ± 0.81) when subjects were tested at the same absolute workload (P  0.05). However, whenthey were tested at the same relative workload,R_a,R_d, andR_{d E} were not different,although R_ox was lowerposttraining (5.36 ± 0.15 vs. 4.41 ± 0.42, P  0.05). These results show1) glucose use is directly relatedto exercise intensity; 2) trainingdecreases glucose flux for a given power output;3) when expressed as relativeexercise intensity, training does not affect the magnitude of bloodglucose use during exercise; 4)training alters the pathways of glucose disposal.

     

Effects of training duration on substrate turnover and oxidation during exercise

Phillips, S. M., H. J. Green, M. A. Tarnopolsky, G. J. F. Heigenhauser, R. E. Hill, and S. M. Grant. Effects of training duration on substrate turnover and oxidation during exercise. J. Appl. Physiol. 81(5):2182-2191, 1996.Adaptations in fat and carbohydrate metabolismafter a prolonged endurance training program were examined using stableisotope tracers of glucose([6,6-²H₂]glucose),glycerol([²H₅]glycerol),and palmitate([²H₂]palmitate).Active, but untrained, males exercised on a cycle for 2 h/day[60% pretraining peak O₂consumption (O_{2 peak}) = 44.3 ± 2.4 ml ^· kg^{1 ·} min¹]for a total of 31 days. Three cycle tests (90 min at 60% pretraining O_{2 peak}) wereadministered before training (PRE) and after 5 (5D) and 31 (31D) daysof training. Exercise increased the rate of glucose production(R_a) and utilization(R_d) as well as the rate oflipolysis (glycerol R_a) and freefatty acid turnover (FFA R_a/R_d).At 5D, training induced a 10% (P < 0.05) increase in total fat oxidation because of an increase inintramuscular triglyceride oxidation (+63%,P < 0.05) and a decreased glycogenoxidation (16%, P < 0.05).At 31D, total fat oxidation during exercise increased a further 58%(P < 0.01). The pattern of fatutilization during exercise at 31D showed a reduced reliance on plasmaFFA oxidation (FFA R_d) and agreater dependence on oxidation of intramuscular triglyceride, whichincreased more than twofold (P < 0.001). In addition, glucose R_aand R_d were reduced at all timepoints during exercise at 31D compared with PRE and 5D. We concludethat long-term training induces a progressive increase in fatutilization mediated by a greater oxidation of fats from intramuscularsources and a reduction in glucose oxidation. Initial changes arepresent as early as 5D and occur before increases in muscle maximalmitochondrial enzyme activity [S. M. Phillips, H. J. Green, M. A. Tarnopolsky, G. J. F. Heigenhauser, and S. M. Grant.Am. J. Physiol. 270 (Endocrinol. Metab. 33):E265-E272, 1996].

     

Short-term 17{beta}-estradiol decreases glucose Ra but not whole body metabolism during endurance exercise

The female sexhormone 17-estradiol (E₂) has been shown to increaselipid and decrease carbohydrate utilization in animals. Weadministrated oral E₂ and placebo (randomized, doubleblind, crossover) to eight human male subjects for 8 days (~3 mg/day) and measured respiratory variables, plasma substrates, hormones (E₂, testosterone, leptin, cortisol, insulin, andcatecholamines), and substrate utilization during 90 min of enduranceexercise. [6,6-²H]glucose and[1,1,2,3,3-²H]glycerol tracers were used to calculatesubstrate flux. E₂ administration increased serumE₂ (0.22 to 2.44 nmol/l, P < 0.05) anddecreased serum testosterone (19.4 to 11.5 nmol/l, P < 0.05) concentrations, yet there were no treatment effects on any of theother hormones. Glucose rates of appearance (R_a) anddisappearance (R_d) were lower, and glycerolR_a-to-R_d ratio was not affected byE₂ administration. O₂ uptake, CO₂production, and respiratory exchange ratio were not affected byE₂; however, there was a decrease in heart rate (P < 0.05). Plasma lactate and glycerol wereunaffected by E₂; however, glucose was significantly higher(P < 0.05) during exercise after E₂administration. We concluded that short-term oral E₂ administration decreased glucose R_a and R_d,maintained plasma glucose homeostasis, but had no effect on substrateoxidation during exercise in men.

     

Effect of increased blood glucose availability on glucose kinetics during exercise

This studyexamined the effect of increased blood glucose availability on glucosekinetics during exercise. Five trained men cycled for 40 min at 77 ± 1% peak oxygen uptake on two occasions. During the second trial(Glu), glucose was infused at a rate equal to the average hepaticglucose production (HGP) measured during exercise in the control trial(Con). Glucose kinetics were measured by a primed continuous infusionofD-[3-³H]glucose.Plasma glucose increased during exercise in both trials and wassignificantly higher in Glu. HGP was similar at rest (Con, 11.4 ± 1.2; Glu, 10.6 ± 0.6µmol · kg¹ · min¹).After 40 min of exercise, HGP reached a peak of 40.2 ± 5.5 µmol · kg¹ · min¹in Con; however, in Glu, there was complete inhibition of the increasein HGP during exercise that never rose above the preexercise level. Therate of glucose disappearance was greater(P < 0.05) during the last 15 min ofexercise in Glu. These results indicate that an increase in glucoseavailability inhibits the rise in HGP during exercise, suggesting thatmetabolic feedback signals can override feed-forward activation of HGPduring strenuous exercise.

     

Effect of luteal phase elevation in core temperature on forearm blood flow during exercise

Kolka, Margaret A., and Lou A. Stephenson. Effect ofluteal phase elevation in core temperature on forearm blood flow duringexercise. J. Appl. Physiol. 82(4):1079-1083, 1997.Forearm blood flow (FBF) as an index of skinblood flow in the forearm was measured in five healthy women by venousocclusion plethysmography during leg exercise at 80% peak aerobicpower and ambient temperature of 35°C (relative humidity 22%;dew-point temperature 10°C). Resting esophagealtemperature (T_es) was 0.3 ± 0.1°C higher in the midluteal than in the early follicular phase ofthe menstrual cycle (P < 0.05).Resting FBF was not different between menstrual cycle phases. TheT_es threshold for onset of skinvasodilation was higher (37.4 ± 0.2°C) in midluteal than inearly follicular phase (37.0 ± 0.1°C; P < 0.05). The slope of the FBF toT_es relationship was not different between menstrual cycle phases (14.0 ± 4.2 ml · 100 ml¹ · min¹ · °C¹for early follicular and 16.3 ± 3.2 ml · 100 ml¹ · min¹ · °C¹for midluteal phase). Plateau FBF was higher during exercise inmidluteal (14.6 ± 2.2 ml · 100 ml¹ · min¹ · °C¹)compared with early follicular phase (10.9 ± 2.4 ml · 100 ml¹ · min¹ · °C¹;P < 0.05). The attenuation of theincrease in FBF to T_es occurred when T_es was 0.6°C higher andat higher FBF in midluteal than in early follicular experiments(P < 0.05). In summary, the FBF response is different during exercise in the two menstrual cycle phasesstudied. After the attenuation of the increase in FBF and whileT_es was still increasing, thegreater FBF in the midluteal phase may have been due to the effects ofincreased endogenous reproductive endocrines on the cutaneousvasculature.

     

Changes in maximum oxygen uptake during prolonged training, overtraining, and detraining in horses

Tyler, Catherine M., Lorraine C. Golland, David L. Evans,David R. Hodgson, and Reuben J. Rose. Changes in maximum oxygenuptake during prolonged training, overtraining, and detraining inhorses. J. Appl. Physiol. 81(5):2244-2249, 1996.Thirteen standardbred horses were trained asfollows: phase 1 (endurance training, 7 wk),phase 2 (high-intensity training, 9 wk),phase 3 (overload training, 18 wk), andphase 4 (detraining, 12 wk). Inphase 3, the horses were divided intotwo groups: overload training (OLT) and control (C). The OLT groupexercised at greater intensities, frequencies, and durations than groupC. Overtraining occurred after 31 wk of training and was defined as asignificant decrease in treadmill run time in response to astandardized exercise test. In the OLT group, there was a significantdecrease in body weight (P < 0.05).From pretraining values of 117 ± 2 (SE)ml ^· kg^{1 ·} min¹,maximal O₂ uptake(O_{2 max}) increased by15% at the end of phase 1, and when signs of overtraining werefirst seen in the OLT group,O_{2 max} was 29%higher (151 ± 2 ml ^· kg^{1 ·} min¹in both C and OLT groups) than pretraining values. There was nosignificant reduction inO_{2 max} until after 6 wk detraining whenO_{2 max} was 137 ± 2 ml ^· kg^{1 ·} min¹.By 12 wk detraining, meanO_{2 max} was134 ± 2 ml ^· kg^{1 ·} min¹,still 15% above pretraining values. When overtraining developed, O_{2 max} was notdifferent between C and OLT groups, but maximal values forCO₂ production (147 vs. 159 ml ^· kg^{1 ·} min¹)and respiratory exchange ratio (1.04 vs. 1.11) were lower in the OLTgroup. Overtraining was not associated with a decrease inO_{2 max} and, afterprolonged training, decreases inO_{2 max} occurredslowly during detraining.

     

Role for anions in pulmonary endothelial permeability

Griffin, M. Pamela. Role for anions in pulmonaryendothelial permeability. J. Appl.Physiol. 83(2): 615-622, 1997.-Adrenergic stimulation reduces albumin permeation across pulmonary artery endothelial monolayers and induces changes in cell morphology that aremediated by Cl flux. Wetested the hypothesis that anion-mediated changes in endothelial cellsresult in changes in endothelial permeability. We measured permeationof radiolabeled albumin across bovine pulmonary arterial endothelialmonolayers when the extracellular anion was Cl,Br,I,F, acetate(Ac), gluconate(G), and propionate(Pr). Permeability toalbumin (P_albumin)was calculated before and after addition of 0.2 mM of thephosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), whichreduces permeability. InCl, theP_albumin was 3.05 ± 0.86 × 10⁶ cm/s andfell by 70% with the addition of IBMX. The initialP_albumin was lowest forPr andAc. InitialP_albumin was higher inBr,I,G, andF than inCl. A permeability ratiowas calculated to examine the IBMX effect. The greatest IBMX effect wasseen when Cl was theextracellular anion, and the order among halide anions wasCl > Br > I > F. Although the level ofextracellular Ca²⁺ concentration([Ca²⁺]_o)varied over a wide range in the anion solutions,[Ca²⁺]_odid not systematically affect endothelial permeability in this system.When Cl was theextracellular anion, varying[Ca²⁺]_ofrom 0.2 to 2.8 mM caused a change in initialP_albumin but no changein the IBMX effect. The anion channel blockers4-acetamido-4-isothiocyanotostilbene-2,2-disulfonic acid(0.25 mM) and anthracene-9-carboxylic acid (0.5 mM) significantly altered initialP_albumin and the IBMXeffect. The anion transport blockers bumetanide (0.2 mM) and furosemide(1 mM) had no such effects. We conclude that extracellular anionsinfluence bovine pulmonary arterial endothelial permeability and thatthe pharmacological profile fits better with the activity of anionchannels than with other anion transport processes.

     

Effects of nitric oxide on blood flow distribution and O2 extraction capabilities during endotoxic shock

Zhang, Haibo, Peter Rogiers, Nadia Smail, Ana Cabral,Jean-Charles Preiser, Marie-Odile Peny, and Jean-Louis Vincent.Effects of nitric oxide on blood flow distribution andO₂ extraction capabilities duringendotoxic shock. J. Appl. Physiol.83(4): 1164-1173, 1997.The effects of the nitric oxide (NO)synthase inhibitorN^G-monomethyl-L-arginine(L-NMMA) and the NO donor3-morpholinosydnonimine (SIN-1) were tested in 18 endotoxic dogs. L-NMMA infusion(10 mg · kg¹ · h¹)increased arterial and pulmonary artery pressures and systemic andpulmonary vascular resistances but decreased cardiac index, leftventricular stroke work index, and blood flow to the hepatic, portal,mesenteric, and renal beds. SIN-1 infusion (2 µg · kg¹ · min¹)increased cardiac index; left ventricular stroke work index; andhepatic, portal, and mesenteric blood flow. It did not significantly influence arterial and pulmonary artery pressures but decreased renalblood flow. The critical O₂delivery was similar in the L-NMMA group and in the controlgroup (13.3 ± 1.6 vs. 12.8 ± 3.3 ml · kg¹ · min¹)but lower in the SIN-1 group (9.1 ± 1.8 ml · kg¹ · min¹,both P < 0.05). The criticalO₂ extraction ratio was alsohigher in the SIN-1 group than in the other groups (58.7 ± 10.6 vs.42.2 ± 7.6% in controls, P < 0.05; 43.0 ± 15.5% inL-NMMA group,P = not significant). We conclude thatNO is not implicated in the alterations inO₂ extraction capabilitiesobserved early after endotoxin administration.

     

Contraction-induced increase in Vmax of palmitate uptake and oxidation in perfused skeletal muscle

To evaluate the effects of contractions on thekinetics of uptake and oxidation of palmitate in a physiological musclepreparation, rat hindquarters were perfused with glucose (6 mmol/l),albumin-bound [1-¹⁴C]palmitate, andvarying amounts of albumin-bound palmitate (200-2,200 µmol/l) atrest and during muscle contractions. When plotted against the unboundpalmitate concentration, palmitate uptake and oxidation displayedsimple Michaelis-Menten kinetics with estimated maximal velocity(V_max)and Michaelis-Menten constant(K_m) values of42.8 ± 3.8 (SE)nmol · min¹ · g¹and 13.4 ± 3.4 nmol/l for palmitate uptake and 3.8 ± 0.4 nmol · min¹ · g¹and 8.1 ± 2.9 nmol/l for palmitate oxidation, respectively, at rest.Whereas muscle contractions increased theV_maxfor both palmitate uptake and oxidation to 91.6 ± 10.1 and 16.5 ± 2.3 nmol · min¹ · g¹,respectively, theK_m remainedunchanged.V_maxand K_m estimates obtained from Hanes-Woolf plots (substrate concentration/velocity vs.substrate concentration) were not significantly different. In theresting perfused hindquarter, an increase in palmitate delivery from31.9 ± 0.9 to 48.7 ± 1.2 µmol · g¹ · h¹by increasing perfusate flow was associated with a decrease in thefractional uptake of palmitate so that the rates of uptake andoxidation of palmitate remained unchanged. It is concluded that therates of uptake and oxidation of long-chain fatty acids (LCFA) saturatewith an increase in the concentration of unbound LCFA in perfusedskeletal muscle and that muscle contractions, but not an increase inplasma flow, increase theV_maxfor LCFA uptake and oxidation. The data are consistent with the notion that uptake of LCFA in muscle may be mediated in part by a transport system.

     

Exogenous glucose oxidation during exercise in endurance-trained and untrained subjects

Jeukendrup, A. E., M. Mensink, W. H. M. Saris, and A. J. M. Wagenmakers. Exogenous glucose oxidation during exercise in endurance-trained and untrained subjects. J. Appl.Physiol. 82(3): 835-840, 1997.To investigate theeffect of training status on the fuel mixture used during exercise withglucose ingestion, seven endurance-trained cyclists (Tr; maximumO₂ uptake 67 ± 2.3 ml ^· kg^{1 ·} min¹)and eight untrained subjects (UTr; 48 ± 2 ml ^· kg^{1 ·} min¹)were studied during 120 min of exercise at ~60% maximumO₂ uptake. At the onset of exercise, 8 ml ^· kg^{1 ·} min¹of an 8% naturally enriched[¹³C]glucose solutionwas ingested and 2 ml/kg every 15 min thereafter. Energy expenditurewas higher in Tr subjects compared with UTr subjects (3,404 vs. 2,630 kJ; P < 0.01). During the secondhour, fat oxidation was higher in Tr subjects (37 ± 2 g) comparedwith UTr subjects (23 ± 1 g), whereas carbohydrateoxidation was similar (116 ± 8 g in Tr subjects vs. 114 ± 4 g in UTr subjects). No differences were observed in exogenousglucose oxidation (50 ± 2 g in Tr subjects and 45 ± 3 g in UTr subjects, respectively). Peak exogenous glucose oxidationrates were similar in the two groups (0.95 ± 0.07 g/min in Trsubjects and 0.96 ± 0.03 g/min in UTr subjects). It is concluded that the higher energy expenditure in Tr subjects during exercise atthe same relative exercise intensity is entirely met by a higher rateof fat oxidation without changes in the rates of exogenous andendogenous carbohydrates.

     

Mechanical and metabolic determination of VO2 and fatigue during repetitive isometric contractions in situ

Repetitiveisometric tetanic contractions (1/s) of the caninegastrocnemius-plantaris muscle were studied either at optimal length(L_o) or shortlength (L_s;~0.9 · L_o),to determine the effects of initial length on mechanical and metabolicperformance in situ. Respective averages of mechanical and metabolicvariables were(L_o vs.L_s, allP < 0.05) passive tension (preload) = 55 vs. 6 g/g, maximal active tetanic tension(P_o) = 544 vs. 174 (0.38 · P_o)g/g, maximal blood flow () = 2.0 vs. 1.4 ml · min¹ · g¹,and maximal oxygen uptake(O₂) = 12 vs. 9 µmol · min¹ · g¹.Tension at L_odecreased to0.64 · P_o over20 min of repetitive contractions, demonstrating fatigue; there were nosignificant changes in tension atL_s. In separatemuscles contracting atL_o, was set to that measured atL_s (1.1 ml · min¹ · g¹),resulting in decreased O₂(7 µmol · min¹ · g¹),and rapid fatigue, to0.44 · P_o. Thesedata demonstrate that 1)muscles at L_ohave higher andO₂ values than those at L_s;2) fatigue occurs atL_o with highO₂, adjusting metabolic demand (tension output) to match supply; and3) the lack of fatigue atL_s with lowertension, , andO₂ suggestsadequate matching of metabolic demand, set low by shortmuscle length, with supply optimized by low preload. Thesedifferences in tension andO₂ betweenL_o andL_s groupsindicate that muscles contracting isometrically at initial lengthsshorter than L_oare working under submaximal conditions.

     

Diffusional permeability of rabbit mesothelium

Diffusional permeability (P) to sucrose(P_suc) andNa⁺(P_Na⁺)was determined in specimens of rabbit sternal parietal pericardium,which may be obtained without stripping. Specimens were mounted in anUssing apparatus with ³H-labeledsucrose and²²Na⁺in a luminal (L) or interstitial (I) chamber.P_suc was 2.16 ± 0.44 for LI and 2.63 ± 0.45 (SE) × 10⁵ cm/s for IL,i.e., ~10 times smaller than that previously obtained in strippedspecimens of pleura despite the similarity of intercellular junctionsin pericardium and pleural mesothelium of various species. Thesefindings suggest that previousP_suc wasoverestimated because stripping damages the mesothelium.P_Na⁺ (×10⁵ cm/s) was 7.07 ± 0.71 for LI and 7.37 ± 0.69 × 10⁵ cm/s for IL.Measurements were also done with phospholipids, which are adsorbed onthe luminal side of mesothelium in vivo. With phospholipids in L,P_suc was 0.75 ± 0.10 and 0.65 ± 0.08 andP_Na⁺was 3.80 ± 0.32 and 3.76 ± 0.15 × 10⁵ cm/s for LI andIL, respectively, i.e., smaller than without phospholipids.With phospholipids in I (where they are not adsorbed), P_suc (2.33 ± 0.42 × 10⁵ cm/s) andP_Na⁺(7.01 ± 0.45 × 10⁵ cm/s) were similar tothose values without phospholipids. Hence, adsorbed phospholipidsdecrease P of mesothelium. If themesothelium were scraped away from the specimen,P_suc of theconnective tissue would be 13.2 ± 0.76 × 10⁵ cm/s.P_suc of themesothelium, computed fromP_suc of theunscraped and scraped specimens, corrected for the effect of unstirredlayers (2.54 and 19.4 × 10⁵ cm/s, respectively),was 2.92 and 0.74 × 10⁵ cm/s without and withphospholipids, respectively. Hence, most of the resistance to diffusionof the pericardium is provided by the mesothelium.

     

Smaller lungs in women affect exercise hyperpnea

We subjected 29 healthy young women (age: 27 ± 1 yr) with a wide range of fitness levels [maximal oxygenuptake (O_{2 max}): 57 ± 6 ml · kg¹ · min¹;35-70ml · kg¹ · min¹]to a progressive treadmill running test. Our subjects had significantly smaller lung volumes and lower maximal expiratory flow rates, irrespective of fitness level, compared with predicted values for age-and height-matched men. The higher maximal workload in highly fit(O_{2 max} > 57 ml · kg¹ · min¹,n = 14) vs. less-fit(O_{2 max} < 56 ml · kg¹ · min¹,n = 15) women caused a higher maximalventilation (E) with increased tidal volume (VT)and breathing frequency (f_b) atcomparable maximal VT/vitalcapacity (VC). More expiratory flow limitation (EFL; 22 ± 4% ofVT) was also observed duringheavy exercise in highly fit vs. less-fit women, causing higherend-expiratory and end-inspiratory lung volumes and greater usage oftheir maximum available ventilatory reserves.HeO₂ (79% He-21%O₂) vs. room air exercise trialswere compared (with screens added to equalize external apparatusresistance). HeO₂ increasedmaximal expiratory flow rates (20-38%) throughout the range ofVC, which significantly reduced EFL during heavy exercise. When EFL wasreduced with HeO₂, VT,f_b, andE (+16 ± 2 l/min) weresignificantly increased during maximal exercise. However, in theabsence of EFL (during room air exercise),HeO₂ had no effect onE. We conclude that smaller lungvolumes and maximal flow rates for women in general, and especiallyhighly fit women, caused increased prevalence of EFL during heavyexercise, a relative hyperinflation, an increased reliance onf_b, and a greater encroachment onthe ventilatory "reserve." Consequently,VT andE are mechanically constrained duringmaximal exercise in many fit women because the demand for highexpiratory flow rates encroaches on the airways' maximum flow-volumeenvelope.

     

Hypoxia- and normoxia-induced reversibility of autonomic control in Andean guinea pig heart

León-Velarde, Fabiola, Jean-Paul Richalet, Juan-CarlosChavez, Rachid Kacimi, Maria Rivera-Chira, José-Antonio Palacios, and Daniel Clark. Hypoxia- and normoxia-induced reversibility ofautonomic control in Andean guinea pig heart. J. Appl.Physiol. 81(5): 2229-2234, 1996.We hereindescribe the regulation of cardiac receptors in a typical high-altitudenative animal. Heart rate response to isoproterenol(HR_Iso)(beats ^· min^{1 ·} mgIso ^· kg¹)and atropine, the density of -adrenergic(_AR) and muscarinic (M₂) receptors, and theventricular content of norepinephrine (NE) and dopamine (DA) werestudied in guinea pigs (Caviaporcellus). Animals native to Lima, Peru (150 m) werestudied at sea level (SL) and after 5 wk at 4,300-m altitude (SL-HA).Animals native to Rancas [Pasco, Peru (4,300 m)] werestudied at high altitude (HA) and after 5 wk at SL (HA-SL). HA animalshad a lower HR_Iso, maximum numberof _AR binding sites(B_max),_AR dissociation constant (K_d), NE, andDA (P < 0.05) and a higherM₂B_max(P < 0.001) when compared with theSL group. HA-SL showed an increase of theHR_Iso, _ARK_d, and NE(P < 0.05) and a decrease of theM₂B_max andK_d (P < 0.0001) when compared with theHA group. The present study demonstrates the differential regulationand reversibility of the autonomic control in the guinea pig heart.

     

Fluid regulatory hormone response to exercise after coca-induced body fluid shifts

Favier, R., E. Caceres, B. Sempore, J. M. Cottet-Emard, G. Gauquelin, C. Gharib, and H. Spielvogel. Fluidregulatory hormone response to exercise after coca-induced body fluidshifts. J. Appl. Physiol. 83(2):376-382, 1997.To determine the effect of coca chewing on heartrate (HR), mean arterial blood pressure (MAP), and plasma volume andtheir relationship with the hormones regulating cardiovascular and bodyfluid homeostasis, 16 male volunteers were examined at rest and during1 h of cycle exercise at ~75% of their peak oxygen uptake in twotrials separated by 1 mo. One trial was performed after the subjectschewed a sugar-free chewing gum(Coca trial), whereas theother was done after the subjects chewed 15 g of coca leaves(Coca⁺), with the order of theCoca andCoca⁺ trials being randomized.Blood samples were taken at rest, before (R₁) and after 1-h chewing(R₂), and during the 5th, 15th,30th, and 60th min of exercise. They were analyzed for hematocrit,hemoglobin concentration, red blood cell count, plasma proteins, andfor the fluid regulatory hormones, including plasma catecholamines [norepinephrine (NE) and epinephrine], renin, argininevasopressin, and the atrial natriuretic peptide (ANP). During thecontrol trial (Coca),from R₁ toR₂, there was no significantchange in hematologic, hormonal, and cardiovascular status except for asmall increase in plasma NE. In contrast, it can be calculated thatcoca chewing at rest induced a significant hemoconcentration(3.8 ± 1.3% in blood and 7.0 ± 0.7% in plasmavolume), increased NE and MAP, and reduced plasma ANP. Chewing cocabefore exercise reduced the body fluid shifts but enhanced HR responseduring exercise. These effects were not accompanied by changes in NE,epinephrine, renin, and arginine vasopressin plasma levels. Incontrast, plasma ANP response to exercise was lower during theCoca⁺ trial, suggesting thatcentral cardiac filling was reduced by coca use. It is likely that thereduction in body fluid volumes is a major contributing factor to thehigher HR at any given time of exercise after coca chewing.

     

Enhanced muscle glucose uptake facilitates nitrogen efflux from exercised muscle

The hypothesis that glucose ingestion inthe postexercise state enhances the synthesis of glutamine and alaninein the skeletal muscle was tested. Glucose was infused intraduodenallyfor 150 min (44.5 µmol · kg¹ · min¹)beginning 30 min after a 150-min period of exercise(n = 7) or an equivalent durationsedentary period (n = 10) in18-h-fasted dogs. Prior exercise caused a twofold greater increase inlimb glucose uptake during the intraduodenal glucose infusion compared with uptake in sedentary dogs. Arterial glutamine levels fell graduallywith the glucose load in both groups. Net hindlimb glutamine effluxincreased in response to intraduodenal glucose in exercised but notsedentary dogs (P < 0.05-0.01).Arterial alanine levels, depleted by 50% with exercise, rose withintraduodenal glucose in exercised but not sedentary dogs(P < 0.05-0.01). Net hindlimb alanine efflux also rose in exercised dogs in response to intraduodenal glucose (P < 0.05-0.01),whereas it was not different from baseline in sedentary controls forthe first 90 min of glucose infusion. Beyond this point,it, too, rose significantly. We conclude that oral glucosemay facilitate recovery of muscle from prolonged exercise by enhancingthe removal of nitrogen in the form of glutamine andalanine.

     

A simplified strong ion model for acid-base equilibria: application to horse plasma

Constable, Peter D. A simplified strong ion model foracid-base equilibria: application to horse plasma. J. Appl. Physiol. 83(1): 297-311, 1997.TheHenderson-Hasselbalch equation and Stewart's strong ion model arecurrently used to describe mammalian acid-base equilibria. Anomaliesexist when the Henderson-Hasselbalch equation is applied to plasma,whereas the strong ion model does not provide a practical method fordetermining the total plasma concentration of nonvolatile weak acids([A_tot]) and theeffective dissociation constant for plasma weak acids(K_a). Asimplified strong ion model, which was developed from the assumptionthat plasma ions act as strong ions, volatile buffer ions(HCO₃), or nonvolatile buffer ions,indicates that plasma pH is determined by five independent variables:PCO₂, strong ion difference, concentration of individual nonvolatile plasma buffers (albumin, globulin, and phosphate), ionic strength, and temperature. The simplified strong ion model conveys on a fundamental level the mechanism for change in acid-base status, explains many of the anomalies when the Henderson-Hasselbalch equation is applied to plasma,is conceptually and algebraically simpler than Stewart's strong ionmodel, and provides a practical in vitro method for determining[A_tot] andK_a of plasma.Application of the simplified strong ion model toCO₂-tonometered horse plasmaproduced values for[A_tot] (15.0 ± 3.1 meq/l) and K_a(2.22 ± 0.32 × 10⁷ eq/l) that weresignificantly different from the values commonly assumed for humanplasma ([A_tot] = 20.0 meq/l, K_a = 3.0 × 10⁷ eq/l).Moreover, application of the experimentally determined values for[A_tot] andK_a to publisheddata for the horse (known PCO₂,strong ion difference, and plasma protein concentration) predictedplasma pH more accurately than the values for[A_tot] andK_a commonlyassumed for human plasma. Species-specific values for[A_tot] andK_a should beexperimentally determined when the simplified strong ion model (orstrong ion model) is used to describe acid-base equilibria.

     

Upper airway muscle activity and upper airway resistance in young adults during sleep

Henke, Kathe G. Upper airway muscle activity and upperairway resistance in young adults during sleep. J. Appl. Physiol. 84(2): 486-491, 1998.To determinethe relationship between upper airway muscle activity and upper airwayresistance in nonsnoring and snoring young adults, 17 subjects werestudied during sleep. Genioglossus and alae nasi electromyogramactivity were recorded. Inspiratory and expiratory supraglotticresistance (Rinsp and Rexp, respectively) were measured at peak flow,and the coefficients of resistance(K_insp andK_exp,respectively) were calculated. Data were recorded during control,with continuous positive airway pressure (CPAP), and on the breathimmediately after termination of CPAP. Rinsp during control averaged 7 ± 1 and 10 ± 2 cmH₂O · l¹ · sand K_inspaveraged 26 ± 5 and 80 ± 27 cmH₂O · l¹ · s²in the nonsnorers and snorers, respectively(P = not significant). Onthe breath immediately after CPAP,K_insp did notincrease over control in snorers (80 ± 27 for control vs. 46 ± 6 cmH₂O · l¹ · s²for the breath after CPAP) or nonsnorers (26 ± 5 vs. 29 ± 6 cmH₂O · l¹ · s²).These findings held true for Rinsp.K_exp did notincrease in either group on the breath immediately after termination ofCPAP. Therefore, 1) increases inupper airway resistance do not occur, despite reductions inelectromyogram activity in young snorers and nonsnorers, and2) increases in Rexp and expiratoryflow limitation are not observed in young snorers.

     

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.