Lactate and epinephrine during exercise in altitude natives

Kayser, Bengt, Roland Favier, Guido Ferretti, DominiqueDesplanches, Hilde Spielvogel, Harry Koubi, Brigitte Sempore, and HansHoppeler. Lactate and epinephrine during exercise in altitudenatives. J. Appl. Physiol. 81(6):2488-2494, 1996.We tested the hypothesis that the reported lowblood lactate accumulation ([La]) during exercise inaltitude-native humans is refractory to hypoxia-normoxia transitions byinvestigating whether acute changes in inspiredO₂ fraction(FI_O2) affect the[La] vs. power output ()relationship or, alternatively, as reported for lowlanders, whetherchanges in [La] vs. on changes inFI_O2 are related tochanges in blood epinephrine concentration ([Epi]). Altitude natives [n = 8, age 24 ± 1 (SE) yr, body mass 62 ± 3 kg, height 167 ± 2 cm]in La Paz, Bolivia (3,600 m) performed incremental exercise with twolegs and one leg in chronic hypoxia and acute normoxia (AN). Submaximalone- and two-leg O₂ uptake (O₂) vs. relationships were not altered byFI_O2. AN increased two-legpeak O₂ by 10% and peak by 7%. AN paradoxically decreasedone-leg peak O₂ by 7%,whereas peak remained the same. The[La] vs. relationships were similar tothose reported in unacclimatized lowlanders. There was a shift to theright on AN, and maximum [La] was reduced by 7 and 8% forone- and two-leg exercises, respectively. [Epi] and[La] were tightly related (mean r = 0.81) independently ofFI_O2. Thus normoxiaattenuated the increment in both [La] and [Epi]as a function of , whereas the correlation between[La] and [Epi] was unaffected. These data suggest loose linkage of glycolysis to oxidative phosphorylation under influence from [Epi]. In conclusion, high-altitudenatives appear to be not fundamentally different from lowlanders with regard to the effect of acute changes inFI_O2 on [La] during exercise.

     

Quantitative analysis of transpleural flux in the isolated lung

Li, M. H., J. Hildebrandt, and M. P. Hlastala.Quantitative analysis of transpleural flux in the isolated lung.J. Appl. Physiol. 82(2): 545-551, 1997.In this study, the loss of inert gas through the pleura of anisolated ventilated and perfused rabbit lung was assessed theoreticallyand experimentally. A mathematical model was used to represent an idealhomogeneous lung placed within a box with gas flow(box) surrounding the lung. Thealveoli are assumed to be ventilated with room air(A) andperfused at constant flow () containinginert gases (x) with various perfusate-air partition coefficients(_p,x).The ratio of transpleural flux of gas(pl_x)to its total delivery to the lung via pulmonary artery( ),representing fractional losses across the pleura, can be shown todepend on four dimensionless ratios:1)_p,x,2) the ratio of alveolar ventilation to perfusion(A/), 3) the ratioof the pleural diffusing capacity(Dpl_x) to the conductance ofthe alveolar ventilation (Dpl_x /A_g,where _g is the capacitancecoefficient of gas), and 4) theratio of extrapleural (box) ventilation to alveolar ventilation(box/A).Experiments were performed in isolated perfused and ventilated rabbitlungs. The perfusate was a buffer solution containing six dissolvedinert gases covering the entire 10⁵-fold range of_p,x usedin the multiple inert gas elimination technique. Steady-state inert gasconcentrations were measured in the pulmonary arterial perfusate,pulmonary venous effluent, exhaled gas, and box effluent gas. Theexperimental data could be described satisfactorily by thesingle-compartment model. It is concluded that a simple theoreticalmodel is a useful tool for predicting transpleural flux from isolatedlung preparations, with known ventilation and perfusion, for inertgases within a wide range of .

     

Combined heart rate and activity improve estimates of oxygen consumption and carbon dioxide production rates

Moon, Jon K., and Nancy F. Butte. Combined heart rateand activity improve estimates of oxygen consumption and carbon dioxideproduction rates. J. Appl. Physiol.81(4): 1754-1761, 1996.Oxygen consumption(O₂) andcarbon dioxide production (CO₂) rates were measuredby electronically recording heart rate (HR) and physical activity (PA).Mean daily O₂ andCO₂ measurements by HR andPA were validated in adults (n = 10 women and 10 men) with room calorimeters. Thirteen linear and nonlinear functions of HR alone and HR combined with PA were tested as models of24-h O₂ andCO₂. Mean sleepO₂ andCO₂ were similar to basalmetabolic rates and were accurately estimated from HR alone[respective mean errors were 0.2 ± 0.8 (SD) and0.4 ± 0.6%]. The range of prediction errorsfor 24-h O₂ andCO₂ was smallestfor a model that used PA to assign HR for each minute to separateactive and inactive curves(O₂, 3.3 ± 3.5%; CO₂, 4.6 ± 3%). There were no significant correlations betweenO₂ orCO₂ errors and subject age,weight, fat mass, ratio of daily to basal energy expenditure rate, orfitness. O₂,CO₂, and energy expenditurerecorded for 3 free-living days were 5.6 ± 0.9 ml ^· min^{1 ·} kg¹,4.7 ± 0.8 ml ^· min^{1 ·} kg¹,and 7.8 ± 1.6 kJ/min, respectively. Combined HR and PA measured 24-h O₂ andCO₂ with a precisionsimilar to alternative methods.

     

Association of chest wall motion and tidal volume responses during CO2 rebreathing

Yan, Sheng, Pawel Sliwinski, and Peter T. Macklem.Association of chest wall motion and tidal volume responses during CO₂ rebreathing.J. Appl. Physiol. 81(4):1528-1534, 1996.The purpose of this study is to investigate theeffect of chest wall configuration at end expiration on tidal volume(VT) response duringCO₂ rebreathing. In a group of 11 healthy male subjects, the changes in end-expiratory andend-inspiratory volume of the rib cage (Vrc,E andVrc,I, respectively) and abdomen (Vab,E and Vab,I, respectively) measured by linearizedmagnetometers were expressed as a function of end-tidalPCO₂(PET_CO2). The changes inend-expiratory and end-inspiratory volumes of the chest wall(Vcw,E and Vcw,I,respectively) were calculated as the sum of the respectiverib cage and abdominal volumes. The magnetometer coils were placed atthe level of the nipples and 1-2 cm above the umbilicus andcalibrated during quiet breathing against theVT measured from apneumotachograph. TheVrc,E/PET_CO2 slope was quite variable among subjects. It was significantly positive (P < 0.05) in fivesubjects, significantly negative in four subjects(P < 0.05), and not different fromzero in the remaining two subjects. TheVab,E/PET_CO2slope was significantly negative in all subjects(P < 0.05) with a much smallerintersubject variation, probably suggesting a relatively more uniformrecruitment of abdominal expiratory muscles and a variable recruitmentof rib cage muscles during CO₂rebreathing in different subjects. As a group, the meanVrc,E/PET_CO2,Vab,E/PET_CO2, andVcw,E/PET_CO2slopes were 0.010 ± 0.034, 0.030 ± 0.007, and0.020 ± 0.032 l / Torr, respectively;only theVab,E/PET_CO2 slope was significantly different from zero. More interestingly, theindividualVT/PET_CO2slope was negatively associated with theVrc,E/PET_CO2(r = 0.68,P = 0.021) and Vcw,E/PET_CO2slopes (r = 0.63,P = 0.037) but was not associated withtheVab,E/PET_CO2slope (r = 0.40, P = 0.223). There was no correlation oftheVrc,E/PET_CO2 andVcw,E/PET_CO2slopes with age, body size, forced expiratory volume in 1 s, orexpiratory time. The groupVab,I/PET_CO2 slope (0.004 ± 0.014 l / Torr) was not significantlydifferent from zero despite theVT nearly being tripled at theend of CO₂ rebreathing. Inconclusion, the individual VTresponse to CO₂, althoughindependent of Vab,E, is a function ofVrc,E to the extent that as theVrc,E/PET_CO2slope increases (more positive) among subjects, theVT response toCO₂ decreases. These results maybe explained on the basis of the respiratory muscle actions andinteractions on the rib cage.

     

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.

     

Mitochondrial redox state as a potential detector of liver dysoxia in vivo

Dysoxia canbe defined as ATP flux decreasing in proportion toO₂ availability with preserved ATPdemand. Hepatic venous -hydroxybutyrate-to-acetoacetate ratio(-OHB/AcAc) estimates liver mitochondrial NADH/NAD and may detectthe onset of dysoxia. During partial dysoxia (as opposed to anoxia),however, flow may be adequate in some liver regions, diluting effluentfrom dysoxic regions, thereby rendering venous -OHB/AcAc unreliable.To address this concern, we estimated tissue ATP whilegradually reducing liver blood flow of swine to zero in a nuclearmagnetic resonance spectrometer. ATP flux decreasing withO₂ availability was taken asO₂ uptake(O₂) decreasing inproportion to O₂ delivery(O₂);and preserved ATP demand was taken as increasingP_i/ATP.O₂, tissueP_i/ATP, and venous -OHB/AcAcwere plotted againstO₂to identify critical inflection points. Tissue dysoxia required meanO₂for the group to be critical for bothO₂ and forP_i/ATP. CriticalO₂values for O₂ andP_i/ATP of 4.07 ± 1.07 and 2.39 ± 1.18 (SE) ml · 100 g¹ · min¹,respectively, were not statistically significantly different but notclearly the same, suggesting the possibility that dysoxia might havecommenced after O₂ begandecreasing, i.e., that there could have been"O₂ conformity." CriticalO₂for venous -OHB/AcAc was 2.44 ± 0.46 ml · 100 g¹ · min¹(P = NS), nearly the same as that forP_i/ATP, supporting venous -OHB/AcAc as a detector of dysoxia. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector ofdysoxia in liver.

     

Nitric oxide response in exhaled air during an incremental exhaustive exercise

Chirpaz-Oddou, M. F., A. Favre-Juvin, P. Flore, J. Eterradossi, M. Delaire, F. Grimbert, and A. Therminarias. Nitric oxide response in exhaled air during an incremental exhaustive exercise. J. Appl. Physiol. 82(4):1311-1318, 1997.This study examines the response of the exhalednitric oxide (NO) concentration (CNO) and the exhaled NOoutput(NO)during incremental exercise and during recovery in six sedentary women,seven sedentary men, and eight trained men. The protocolconsisted of increasing the exercise intensity by 30 W every 3 minuntil exhaustion, followed by 5 min of recovery. Minute ventilation(E), oxygen consumption (O₂), carbon dioxideproduction, heart rate, CNO, andNOwere measured continuously. TheCNO in exhaled air decreasedsignificantly provided that the exercise intensity exceeded 65% of thepeak O₂. It reached similarvalues, at exhaustion, in all three groups. TheNO increasedproportionally with exercise intensity up to exhaustion and decreasedrapidly during recovery. At exhaustion, the mean values weresignificantly higher for trained men than for sedentary men andsedentary women. During exercise,NOcorrelates well with O₂,carbon dioxide production, E, and heartrate. For the same submaximal intensity, and thus a givenO₂ and probably a similarcardiac output,NO appearedto be similar in all three groups, even if theE was different. These results suggestthat, during exercise,NO is mainlyrelated to the magnitude of aerobic metabolism and that thisrelationship is not affected by gender differences or by noticeabledifferences in the level of physical training.

     

Exercise attenuates {alpha}-adrenergic-receptor responsiveness in skeletal muscle vasculature

Attenuation of sympathetic vasoconstriction(sympatholysis) in working muscles during dynamic exercise iscontroversial. A potential mechanism is a reduction in-adrenergic-receptor responsiveness. The purpose of this study wasto examine ₁- and ₂-adrenergic-receptor-mediated vasoconstriction inresting and exercising skeletal muscle using intra-arterial infusionsof selective agonists. Thirteen mongrel dogs were instrumentedchronically with flow probes on the external iliac arteries of bothhindlimbs and a catheter in one femoral artery. The selective₁-adrenergic agonist (phenylephrine) or the selective₂-adrenergic agonist (clonidine) was infused as a bolusinto the femoral artery catheter at rest and during mild and heavyexercise. Intra-arterial infusions of phenylephrine elicited reductionsin vascular conductance of 76 ± 4, 71 ± 5, and 31 ± 2% at rest, 3 miles/h, and 6 miles/h and 10% grade, respectively.Intra-arterial clonidine reduced vascular conductance by 81 ± 5, 49 ± 4, and 14 ± 2%, respectively. The response tointra-arterial infusion of clonidine was unaffected by surgicalsympathetic denervation. Agonist infusion did not affect eithersystemic blood pressure, heart rate, or blood flow in the contralateraliliac artery. ₁-Adrenergic-receptor responsiveness wasattenuated during heavy exercise. In contrast,₂-adrenergic-receptor responsiveness was attenuated evenat a mild exercise intensity. These results suggest that the mechanismof exercise sympatholysis may involve reductions in postsynaptic-adrenergic-receptor responsiveness.

     

Tumor necrosis factor-alpha in ischemia and reperfusion injury in rat lungs

The effects ofboth recombinant rat tumor necrosis factor- (TNF-) and ananti-TNF- antibody were studied in isolated buffer-perfused ratlungs subjected to either 45 min of nonventilated[ischemia-reperfusion (I/R)] or air-ventilated(/R) ischemia followed by 90 min of reperfusion and ventilation. In the I/R group, the vascularpermeability, as measured by the filtration coefficient(K_fc),increased three- and fivefold above baseline after 30 and 90 min ofreperfusion, respectively (P < 0.001). Over the same time intervals, theK_fc for the/R group increased five- and tenfold above baseline values, respectively (P < 0.001).TNF- measured in the perfusates of both ischemic modelssignificantly increased after 30 min of reperfusion. Recombinant ratTNF- (50,000 U), placed into perfusate after baseline measurements,produced no measurable change in microvascular permeability in controllungs perfused over the same time period (135 min), but I/R injury wassignificantly enhanced in the presence of TNF-. An anti-TNF-antibody (10 mg/rat) injected intraperitoneally into rats 2 h beforethe lung was isolated prevented the microvascular damage in lungsexposed to both I/R and /R (P < 0.001). These results indicatethat TNF- is an essential component at the cascade of events thatcause lung endothelial injury in short-term I/R and/R models of lung ischemia.

     

Contributions of pulmonary perfusion and ventilation to heterogeneity in VA/Q measured by PET

Treppo, Steven, Srboljub M. Mijailovich, and José G. Venegas. Contributions of pulmonary perfusion and ventilation toheterogeneity in A/measured by PET. J. Appl. Physiol. 82(4): 1163-1176, 1997. To estimate the contributions of the heterogeneity in regionalperfusion () and alveolar ventilation(A) to that of ventilation-perfusionratio (A/), we haverefined positron emission tomography (PET) techniques to image localdistributions of andA per unit of gas volume content(s and sA,respectively) and VA/ indogs. sA was assessed in two ways:1) the washout of ¹³NN tracer after equilibrationby rebreathing (sA_i), and2) the ratio of an apneic image after a bolus intravenousinfusion of ¹³NN-saline solution to an image collectedduring a steady-state intravenous infusion of the same solution(sA_p).sA_p was systematically higher than sA_i in allanimals, and there was a high spatial correlation betweens andsA_p in both body positions(mean correlation was 0.69 prone and 0.81 supine) suggesting thatventilation to well-perfused units was higher than to those poorlyperfused. In the prone position, the spatial distributions ofs, sA_p, and A/ were fairlyuniform with no significant gravitational gradients; however, in thesupine position, these variables were significantly more heterogeneous,mostly because of significant gravitational gradients (15, 5.5, and10%/cm, respectively) accounting for 73, 33, and 66% of thecorresponding coefficient of variation (CV)² values. Weconclude that, in the prone position, gravitational forces in blood andlung tissues are largely balanced out by dorsoventral differences inlung structure. In the supine position, effects of gravity andstructure become additive, resulting in substantial gravitationalgradients in s andsA_p, with the higherheterogeneity inA/ caused by agravitational gradient in s, only partially compensated by that in sA.

     

Ventilation-perfusion alterations after smoke inhalation injury in an ovine model

Shimazu, Takeshi, Tetsuo Yukioka, Hisashi Ikeuchi, Arthur D. Mason, Jr., Peter D. Wagner, and Basil A. Pruitt, Jr.Ventilation-perfusion alterations after smoke inhalation injury inan ovine model. J. Appl. Physiol.81(5): 2250-2259, 1996.To study the pathophysiological mechanismof progressive hypoxemia after smoke inhalation injury, alterations inventilation-perfusion ratio(A/)were studied in an ovine model by using the multiple inert gaselimination technique. Because ethane was detected in expired gas ofsome sheep, we replaced ethane with krypton, which was a uniqueapplication of the multiple inert gas elimination technique when one ofthe experimental gases is present in the inspirate. Severity-related changes were studied 24 h after injury in control and mild, moderate, and severe inhalation injury groups. Time-related changes were studiedin controls and sheep with moderate injury at 6, 12, 24, and 72 h.Arterial PO₂ decreased progressivelywith severity of injury as well as with time. In smoke-exposed animals,blood flow was recruited to lowA/compartment (0 < A/ < 0.1; 17.6 ± 10.6% of cardiac output, 24 h,moderate injury) from normal A/compartment (0.1 < A/ < 10). However, increases in true shunt(A/ = 0; 5.6 ± 2.5%, 24 h, moderate injury) and dead space were notconsistent findings. TheA/patterns suggest the primary change in smoke inhalation injury to be adisturbance of ventilation.

     

Vascular tree structure affects lung blood flow heterogeneity simulated in three dimensions

Parker, James C., Chris B. Cave, Jeffrey L. Ardell, CharlesR. Hamm, and Susan G. Williams. Vascular treestructure affects lung blood flow heterogeneity simulated in threedimensions. J. Appl. Physiol. 83(4):1370-1382, 1997.Pulmonary arterial tree structures related toblood flow heterogeneity were simulated by using a symmetrical,bifurcating model in three-dimensional space. The branch angle (),daughter-parent length ratio(r_L), branchrotation angle (), and branch fraction of parent flow () for asingle bifurcation were defined and repeated sequentially through 11 generations. With  fixed at 90°, tree structures were generatedwith  between 60 and 90°,r_L between 0.65 and 0.85, and an initial segment length of 5.6 cm and sectioned into1-cm³ samples for analysis. Bloodflow relative dispersions (RD%) between 52 and 42% and fractaldimensions (D_s)between 1.20 and 1.15 in 1-cm³samples were observed even with equal branch flows. When  0.5, RD% increased, butD_s eitherdecreased with gravity bias of higher branch flows or increased withrandom assignment of higher flows. Blood flow gradients along gravityand centripetal vectors increased with biased flow assignment of higherflows, and blood flows correlated negatively with distance only when   0.5. Thus a recursive branching vascular tree structuresimulated D_s andRD% values for blood flow heterogeneity similar to those observedexperimentally in the pulmonary circulation due to differences in thenumber of terminal arterioles per1-cm³ sample, but blood flowgradients and a negative correlation of flows with distance requiredunequal partitioning of blood flows at branchpoints.

     

Effects of respiratory muscle work on cardiac output and its distribution during maximal exercise

We have recently demonstrated that changes inthe work of breathing during maximal exercise affect leg blood flow andleg vascular conductance (C. A. Harms, M. A. Babcock, S. R. McClaran, D. F. Pegelow, G. A. Nickele, W. B. Nelson, and J. A. Dempsey. J. Appl. Physiol. 82: 1573-1583,1997). Our present study examined the effects of changesin the work of breathing on cardiac output (CO) during maximalexercise. Eight male cyclists [maximalO₂ consumption(O_{2 max}):62 ± 5 ml · kg¹ · min¹]performed repeated 2.5-min bouts of cycle exercise atO_{2 max}. Inspiratorymuscle work was either 1) at controllevels [inspiratory esophageal pressure (Pes): 27.8 ± 0.6 cmH₂O],2) reduced via a proportional-assistventilator (Pes: 16.3 ± 0.5 cmH₂O), or 3) increased via resistive loads(Pes: 35.6 ± 0.8 cmH₂O).O₂ contents measured in arterialand mixed venous blood were used to calculate CO via the direct Fickmethod. Stroke volume, CO, and pulmonaryO₂ consumption(O₂) were not different(P > 0.05) between control andloaded trials atO_{2 max} but were lower(8, 9, and 7%, respectively) than control withinspiratory muscle unloading atO_{2 max}. Thearterial-mixed venous O₂difference was unchanged with unloading or loading. We combined thesefindings with our recent study to show that the respiratory muscle work normally expended during maximal exercise has two significant effectson the cardiovascular system: 1) upto 14-16% of the CO is directed to the respiratory muscles; and2) local reflex vasoconstriction significantly compromises blood flow to leg locomotor muscles.

     

Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise

Barstow, Thomas J., Andrew M. Jones, Paul H. Nguyen, andRichard Casaburi. Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise.J. Appl. Physiol. 81(4):1642-1650, 1996.We tested the hypothesis that the amplitude ofthe additional slow component ofO₂ uptake(O₂) during heavy exerciseis correlated with the percentage of type II (fast-twitch) fibers inthe contracting muscles. Ten subjects performed transitions to a workrate calculated to require aO₂ equal to 50% betweenthe estimated lactate (Lac) threshold and maximalO₂ (50%).Nine subjects consented to a muscle biopsy of the vastus lateralis. Toenhance the influence of differences in fiber type among subjects,transitions were made while subjects were pedaling at 45, 60, 75, and90 rpm in different trials. Baseline O₂ was designed to besimilar at the different pedal rates by adjusting baseline work ratewhile the absolute increase in work rate above the baseline was thesame. The O₂ response after the onset of exercise was described by a three-exponential model. Therelative magnitude of the slow component at the end of 8-min exercisewas significantly negatively correlated with %type I fibers at everypedal rate (r = 0.64 to 0.83, P < 0.05-0.01). Furthermore,the gain of the fast component forO₂ (asml ^· min^{1 ·} W¹)was positively correlated with the %type I fibers across pedal rates(r = 0.69-0.83). Increase inpedal rate was associated with decreased relative stress of theexercise but did not affect the relationships between%fiber type and O₂parameters. The relative contribution of the slow component was alsosignificantly negatively correlated with maximalO₂(r = 0.65), whereas the gainfor the fast component was positively associated(r = 0.68-0.71 across rpm). Theamplitude of the slow component was significantly correlated with netend-exercise Lac at all four pedal rates(r = 0.64-0.84), but Lac was notcorrelated with %type I (P > 0.05).We conclude that fiber type distribution significantly affects both thefast and slow components ofO₂ during heavy exerciseand that fiber type and fitness may have both codependent andindependent influences on the metabolic and gas-exchange responses toheavy exercise.

     

Respiratory muscle work compromises leg blood flow during maximal exercise

Harms, Craig A., Mark A. Babcock, Steven R. McClaran, DavidF. Pegelow, Glenn A. Nickele, William B. Nelson, and Jerome A. Dempsey.Respiratory muscle work compromises leg blood flow during maximalexercise. J. Appl. Physiol.82(5): 1573-1583, 1997.We hypothesized that duringexercise at maximal O₂ consumption (O_{2 max}),high demand for respiratory muscle blood flow() would elicit locomotor muscle vasoconstrictionand compromise limb . Seven male cyclists(O_{2 max} 64 ± 6 ml · kg¹ · min¹)each completed 14 exercise bouts of 2.5-min duration atO_{2 max} on a cycleergometer during two testing sessions. Inspiratory muscle work waseither 1) reduced via aproportional-assist ventilator, 2)increased via graded resistive loads, or3) was not manipulated (control).Arterial (brachial) and venous (femoral) blood samples, arterial bloodpressure, leg (legs;thermodilution), esophageal pressure, andO₂ consumption(O₂) weremeasured. Within each subject and across all subjects, at constantmaximal work rate, significant correlations existed(r = 0.74-0.90;P < 0.05) between work of breathing(Wb) and legs (inverse), leg vascular resistance (LVR), and leg O₂(O_{2 legs};inverse), and between LVR and norepinephrine spillover. Mean arterialpressure did not change with changes in Wb nor did tidal volume orminute ventilation. For a ±50% change from control in Wb,legs changed 2 l/min or 11% of control, LVRchanged 13% of control, and O₂extraction did not change; thusO_{2 legs}changed 0.4 l/min or 10% of control. TotalO_{2 max} was unchangedwith loading but fell 9.3% with unloading; thusO_{2 legs}as a percentage of totalO_{2 max} was 81% incontrol, increased to 89% with respiratory muscle unloading, anddecreased to 71% with respiratory muscle loading. We conclude that Wbnormally incurred during maximal exercise causes vasoconstriction inlocomotor muscles and compromises locomotor muscle perfusion andO₂.

     

Differences in skeletal muscle between men and women with chronic heart failure

Men with chronic heart failure (CHF) have alterationsin their skeletal muscle that are partially responsible for a decreased exercise tolerance. The purpose of this study was to investigate whether skeletal muscle alterations in women with CHF are similar tothose observed in men and if these alterations are related to exerciseintolerance. Twenty-five men and thirteen women with CHFperformed a maximal exercise test for evaluation of peak oxygen consumption (O₂) and resting leftventricular ejection fraction, after which a biopsy of the vastuslateralis was performed. Twenty-one normal subjects (11 women, 10 men)were also studied. The relationship between muscle markers and peakO₂ was consistent for CHF men and women.When controlling for gender, analysis showed that oxidative enzymes andcapillary density are the best predictors of peak O_2. These results indicatethat aerobically matched CHF men and women have no differences inskeletal muscle biochemistry and histology. However, when CHF groupswere separated by peak exercise capacity of 4.5 metabolic equivalents(METs), CHF men with peak O₂ >4.5METs had increased citrate synthase and 3-hydroxyacyl-CoA dehydrogenasecompared with CHF men with peak O₂ <4.5METs. CHF men with a lower peak O₂ hadincreased capillary density compared with men with higher peakO₂. These observations were notreproduced in CHF women. This suggests that differences may existin how skeletal muscle adapts to decreasing peakO₂ in patients with CHF.

     

Effect of prolonged heavy exercise on pulmonary gas exchange in horses

During short-term maximal exercise,horses have impaired pulmonary gas exchange, manifested by diffusionlimitation and arterial hypoxemia, without marked ventilation-perfusion(A/)inequality. Whether gas exchange deteriorates progressively duringprolonged submaximal exercise has not been investigated. Sixthoroughbred horses performed treadmill exercise at ~60% of maximaloxygen uptake until exhaustion (28-39 min). Multipleinert gas, blood-gas, hemodynamic, metabolic rate, and ventilatory datawere obtained at rest and 5-min intervals during exercise. Oxygenuptake, cardiac output, and alveolar-arterialPO₂ gradient were unchanged after thefirst 5 min of exercise. Alveolar ventilation increased progressivelyduring exercise, from increased tidal volume and respiratory frequency,resulting in an increase in arterialPO₂ and decrease in arterialPCO₂. At rest there was minimal A/inequality, log SD of the perfusion distribution (logSD) = 0.20. This doubled by 5 min of exercise (logSD = 0.40) butdid not increase further. There was no evidence of alveolar-end-capillary diffusion limitation during exercise. However, there was evidence for gas-phase diffusion limitation at all time points, and enflurane was preferentially overretained. Horses maintainexcellent pulmonary gas exchange during exhaustive, submaximal exercise. AlthoughA/inequality is greater than at rest, it is less than observed in mostmammals and the effect on gas exchange is minimal.

     

Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects

Assisted ventilation with pressure support (PSV)or proportional assist (PAV) ventilation has the potential to produceperiodic breathing (PB) during sleep. We hypothesized that PB willdevelop when PSV level exceeds the product of spontaneous tidal volume (VT) and elastance(VT_sp · E)but that the actual level at which PB will develop[PSV(PB)] will be influenced by thePCO₂ (difference between eupneicPCO₂ andCO₂ apneic threshold) and by RR[response of respiratory rate (RR) to PSV]. We also wishedto determine the PAV level at which PB develops to assess inherentventilatory stability in normal subjects. Twelve normal subjectsunderwent polysomnography while connected to a PSV/PAV ventilatorprototype. Level of assist with either mode was increased in smallsteps (2-5 min each) until PB developed or the subject awakened.End-tidal PCO₂,VT, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated byrespiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from[(Paw + Pmus)/Pmus], where Paw is peak Paw  continuous positive airway pressure. PB with central apneas developedin 11 of 12 subjects on PSV. PCO₂ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small andbidirectional (+1.1 to 3.5min¹). With use ofstepwise regression, PSV(PB) was significantly correlated withVT_sp(P = 0.001), E(P = 0.00009),PCO₂ (P = 0.007), and RR(P = 0.006). The final regressionmodel was as follows: PSV(PB) = 11.1 VT_sp + 0.3E  0.4 PCO₂  0.34 RR  3.4 (r = 0.98). PBdeveloped in five subjects on PAV at amplification factors of1.5-3.4. It failed to occur in seven subjects, despite PAF of upto 7.6. We conclude that 1) aPCO₂ apneic threshold exists duringsleep at 1.5-5.8 Torr below eupneicPCO₂,2) the development of PB during PSVis entirely predictable during sleep, and3) the inherent susceptibility to PBvaries considerably among normal subjects.

     

Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of alpha 1- and alpha 2-adrenoceptor activation

Zschauer, A. O. A., M. W. Sielczak, D. A. S. Smith, and A. Wanner. Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of ₁-and ₂-adrenoceptor activation. J. Appl. Physiol. 82(6):1918-1925, 1997.The contractile effect of norepinephrine (NE) onisolated rabbit bronchial artery rings (150-300 µm in diameter)and the role of ₁- and₂-adrenoceptors (AR) on smoothmuscle and endothelium were studied. In intact arteries, NE increasedtension in a dose-dependent manner, and the sensitivity for NE wasfurther increased in the absence of endothelium. In intact but not inendothelium-denuded arteries, the response to NE was increased in thepresence of both indomethacin (Indo; cyclooxygenase inhibitor) andN^G-nitro-L-argininemethyl ester [L-NAME;nitric oxide (NO) synthase inhibitor], indicating that twoendothelium-derived factors, NO and a prostanoid, modulate theNE-induced contraction. The₁-AR antagonist prazosinshifted the NE dose-response curve to the right, and phenylephrine(₁-AR agonist) induced adose-dependent contraction that was potentiated byL-NAME or removal of theendothelium. The sensitivity to NE was increased slightly by the₂-AR antagonists yohimbine andidazoxan, and this effect was abolished by Indo or removal of theendothelium. Similarly, contractions induced by UK-14304(₂-AR agonist) were potentiatedby Indo or removal of the endothelium. These results suggest thatNE-induced contraction is mediated through activation of₁- and₂-ARs on both smooth muscle andendothelium. Activation of the₁- and₂-ARs on the smooth musclecauses contraction, whereas activation of the endothelial ₁- and₂-ARs induces relaxationthrough release of NO (₁-ARs) and a prostanoid (₂-ARs).

     

Muscle capillarization, O2 diffusion distance, and VO2 kinetics in old and young individuals

Chilibeck, P. D., D. H. Paterson, D. A. Cunningham, A. W. Taylor, and E. G. Noble. Muscle capillarization,O₂ diffusion distance, andO₂ kinetics in old andyoung individuals. J. Appl. Physiol.82(1): 63-69, 1997.The relationships between muscle capillarization, estimated O₂diffusion distance from capillary to mitochondria, andO₂ uptake(O₂) kineticswere studied in 11 young (mean age, 25.9 yr) and 9 old (mean age, 66.0 yr) adults. O₂kinetics were determined by calculating the time constants () forthe phase 2 O₂ adjustment to andrecovery from the average of 12 repeats of a 6-min, moderate-intensityplantar flexion exercise. Muscle capillarization was determined fromcross sections of biopsy material taken from lateral gastrocnemius.Young and old groups had similarO₂ kinetics(O₂-on = 44 vs. 48 s;O₂-off = 33 vs. 44 s, for young and old, respectively), muscle capillarization, andestimated O₂ diffusion distances.Muscle capillarization, expressed as capillary density or averagenumber of capillary contacts per fiber/average fiber area, and theestimates of diffusion distance were significantly correlated toO₂-off kinetics in theyoung (r = 0.68 to 0.83;P < 0.05). We conclude that1) capillarization andO₂ kinetics during exerciseof a muscle group accustomed to everyday activity (e.g., walking) arewell maintained in old individuals, and2) in the young, recovery of O₂ after exercise isfaster, with a greater capillary supply over a given muscle fiber areaor shorter O₂ diffusion distances.