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.

     

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.

     

Dissociation between hysteresivity and tension in constricted tracheal and parenchymal strips

The object of this study was to investigatehow changes in the contractile state of smooth muscle would modifyoscillatory mechanics of tracheal muscle and lung parenchyma duringagonist challenge. Guinea pig tracheal and parenchymal lung strips were suspended in an organ bath. Measurements of length(L) and tension (T) were recordedduring sinusoidal oscillations under baseline conditions and afterchallenge with 1 mM ACh. Measurements were also obtained in stripspretreated with the calmodulin inhibitor calmidazolium (Cmz) orstaurosporine (Stauro), a protein kinase C inhibitor. Elastance (E) andresistance (R) were calculated by fitting changes in T,L, andL/tto the equation of motion. Hysteresivity () was obtained from thefollowing equation: = (R/E)2f,where f is frequency. Finally, maximalunloaded shortening velocity during electrical field stimulation wasmeasured in Cmz-pretreated and control tracheal strips. In trachealstrips, pretreatment with Cmz caused a significant decrease in the  response to ACh challenge and in maximal unloaded shortening velocitymeasured during electrical field stimulation; Stauro decreased the T,E, and R response to ACh. In parenchymal strips, Cmz decreased the  response, whereas Stauro had no effect. These results suggest thatmodifications in the contractile state of the smooth muscle arereflected in changes in the hysteretic behavior and that T and  maybe controlled independently. Second, inasmuch as changes in  weresimilar in parenchymal and tracheal strips, the contractile element isimplicated as the structure responsible for constriction-induced changes in the mechanical behavior of the lung periphery.

     

Reduced blood flow in abdominal viscera measured by Doppler ultrasound during one-legged knee extension

The redistributionof blood flow (BF) in the abdominal viscera during right-legged kneeextension-flexion exercise at very low intensity [peak heart rate(HR), 76 beats/min] was examined by using Doppler ultrasound.While sitting, subjects performed a right-legged knee extension-flexionexercise every 6 s for 20 min. BF was measured in the upper abdominalaorta (Ao), right common femoral artery (RCFA), and left common femoralartery (LCFA). Visceral BF(BF_Vis) was determined by theequation [BF_Ao  (BF_RCFA + BF_LCFA)]. A comparisonwith the change in BF (BF) preexercise showed a greater increase inBF_RCFA than inBF_Ao during exercise. Thisresulted in a reduction of BF_Visto 56% of its preexercise value or a decrease in flow by 1,147 ± 293 (±SE) ml/min at the peak workload. Oxygen consumptioncorrelated positively withBF_Ao, BF_RCFA, andBF_LCFA but inversely withBF_Vis during exercise andrecovery. Furthermore, BF_Vis (% of preexercise value) correlated inversely with both an increase in HR(r = 0.89), and percent peakoxygen consumption (r = 0.99).This study demonstrated that, even during very-low-intensity exercise(HR <90 beats/min), there was a significant shift in BF from theviscera to the exercising muscles.     

Determination of production of nitric oxide by lower airways of humans---theory

Hyde, Richard W., Edgar J. Geigel, Albert J. Olszowka, JohnA. Krasney, Robert E. Forster II, Mark J. Utell, and Mark W. Frampton.Determination of production of nitric oxide by the lower airwaysof humanstheory. J. Appl. Physiol.82(4): 1290-1296, 1997.Exercise and inflammatory lung disorderssuch as asthma and acute lung injury increase exhaled nitric oxide(NO). This finding is interpreted as a rise in production of NO by thelungs (NO)but fails to take into account the diffusing capacity for NO(DNO) that carries NO into thepulmonary capillary blood. We have derived equations to measureNO from thefollowing rates, which determine NO tension in the lungs(PL) at any moment from 1) production(NO);2) diffusion, whereDNO(PL) = rate of removal by lung capillary blood; and3) ventilation, whereA(PL)/(PB  47) = the rate of NO removal by alveolar ventilation(A) and PB is barometric pressure. During open-circuit breathingwhen PL is not in equilibrium,d/dtPL[V_L/(PB  47)] (where V_L is volumeof NO in the lower airways) = NO  DNO(PL)  A(PL)/(PB  47). When PL reaches asteady state so that d/dt = 0 andA iseliminated by rebreathing or breath holding, then PL = NO/DNO.PL can be interpreted as NOproduction per unit of DNO. Thisequation predicts that diseases that diminishDNO but do not alterNO willincrease expired NO levels. These equations permit precise measurementsof NO thatcan be applied to determining factors controlling NO production by thelungs.

     

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.

     

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.

     

Interaction of cross-sectional area, driving pressure, and airflow of passive velopharynx

Isono, Shiroh, Thom R. Feroah, Eric A. Hajduk, Rollin Brant,William A. Whitelaw, and John E. Remmers. Interaction ofcross-sectional area, driving pressure, and airflow of passive velopharynx. J. Appl. Physiol. 83(3):851-859, 1997.Previous studies have shown that, when thepharyngeal muscles are relaxed, the velopharynx is a highly compliantsegment of the pharynx. Thus, under these circumstances,cross-sectional area of the velopharynx (A_VP), drivingpressure across the velopharynx (P), and inspiratory airflow(I) willbe mutually interdependent variables. The purpose of the presentinvestigation was to describe the interrelation among these threevariables during inspiration. We studied 15 sleeping patients withobstructive sleep apnea/hypopnea when the pharyngeal muscles wererendered hypotonic by applying continuous positive airway pressure tothe nasal airway.A_VP, determined by endoscopic imaging, was significantly greater at onset ofI limitationthan at minimum oropharyngeal pressure(P < 0.01). Snoring was neverobserved duringIlimitation. In a subgroup of six patients, values for P,I, andA_VP were obtainedat 0.1-s intervals at various levels of mask pressure. For these sixpatients, the mathematical expressionI = 0.657(A_VP/A_max) · P^0.332,where A_max ismaximal A_VP,described the relationship among the three variables(R² = 0.962) forflow-limited and non-flow-limited inspirations. The impedance of thepassive velopharynx, defined asP^0.33/,was inversely related toA_VP and increaseddramatically when A_VP was <0.3cm². In summary, we observed aprogressive decrease inA_VP during flow-limited inspiration in patients with obstructive sleep apnea. Thisconstriction of the velopharynx contributes to an increase invelopharyngeal impedance that, in turn, counterbalances the increase inP during flow limitation.

     

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.

     

Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled beta -agonists

Carvalho, Paula, Shane R. Johnson, Nirmal B. Charan.Non-cAMP-mediated bronchial arterial vasodilation in response toinhaled -agonists. J. Appl.Physiol. 84(1): 215-221, 1998.We studied thedose-dependent effects of inhaled isoetharine HCl, a -adrenergicbronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow(br) in anesthetized sheep. Isoetharine resulted ina dose-dependent increase in br. With atotal dose of 17.5 mg, br increased from baselinevalues of 22 ± 3.4 (SE) to 60 ± 16 ml/min(P < 0.001), an effect independentof changes in cardiac output and systemic arterial pressure. To furtherstudy whether synthesis of endogenous nitric oxide (NO) affects-agonist-induced increases in br, weadministered isoetharine (20 mg) by inhalation before and after theNO-synthase inhibitorN-nitro-L-argininemethyl ester (L-NAME).Intravenous L-NAME (30 mg/kg) rapidly decreased br by ~80% of baseline,whereas L-NAME via inhalation(10 mg/kg) resulted in a delayed and smaller (~22%) decrease.Pretreatment with L-NAME viaboth routes of administration attenuated bronchial arterialvasodilation after subsequent challenge with isoetharine. We concludethat isoetharine via inhalation increases br in adose-dependent manner and that -agonist-induced relaxation ofvascular smooth muscle in the bronchial vasculature is partiallymediated via synthesis of NO.

     

Liposome encapsulation attenuates hemoglobin-induced vasoconstriction in rabbit arterial segments

Rudolph, Alan S., Anthony Sulpizio, Paul Hieble, VictorMacdonald, Mark Chavez, and Giora Feuerstein. Liposomeencapsulation attenuates hemoglobin-induced vasoconstriction in rabbitarterial segments. J. Appl. Physiol.82(6): 1826-1835, 1997.Free hemoglobin (Hb) induces a potentvasoconstrictor response that may limit its therapeutic application asa red blood cell replacement. We have investigated whetherencapsulation of stroma-free Hb (SFHb) or cross-linked Hb (-Hb)in liposomes modulates Hb vasoactivity in isolated blood vessels.Relaxation of rabbit thoracic vessels was measured before and afterexposure to acellular SFHb, -Hb, and liposome-encapsulated SFHbor -Hb. SFHb and -Hb caused significant inhibition ofcarbachol-induced relaxation at 0.5 mg/dl, whereas encapsulationinhibited vessel relaxation at 30- to 60-fold higher Hb concentrations.The contractile response of rabbit ear arterial segments to electricalstimulation in the presence of acellular -Hb resulted in a 150%increase (EC₁₅₀) in contractileamplitude at 0.23 mg/dl, whereas theEC₁₅₀ for encapsulated -Hbwas 13.7 mg/dl. Mechanistic studies of the vasoconstrictor activity ofHb demonstrated that acellular -Hb had no effect onnorepinephrine release in the rabbit ear artery. In addition, neitheracellular nor encapsulated -Hb preparations inhibited endothelialnitric oxide (NO) synthase activity isolated from bovine pulmonaryartery. However, inhibition of vessel relaxation by acellular orencapsulated -Hb was reversed by the NO donor S-nitrosylpenacillamine, implicatingHb-NO binding as a possible mechanism for the vasoconstrictor response.In vitro stopped-flow kinetic studies of Hb-NO binding showed similarrates of reaction for conversion of oxyhemoglobin to methemoglobin(metHb; <2 ms), followed by rapid conversion of metHb to NO-Hb (300 ms) for both acellular and encapsulated -Hb, demonstrating thatliposome encapsulation does not retard NO-Hb binding. The attenuatedvasoactivity of encapsulated Hb may, therefore, result from the limitedaccess of encapsulated Hb to NO imposed by the physical size of theliposome and reduced penetration of Hb across the vascular endothelium.

     

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 .

     

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.

     

Greater rate of decline in maximal aerobic capacity with age in physically active vs. sedentary healthy women

Tanaka, Hirofumi, Christopher A. DeSouza, Pamela P. Jones,Edith T. Stevenson, Kevin P. Davy, and Douglas R. Seals. Greater rate of decline in maximal aerobic capacity with age in physically active vs. sedentary healthy women. J. Appl.Physiol. 83(6): 1947-1953, 1997.Using ameta-analytic approach, we recently reported that the rate of declinein maximal oxygen uptake(O_{2 max}) with age inhealthy women is greatest in the most physically active and smallest inthe least active when expressed in milliliters per kilogram per minuteper decade. We tested this hypothesis prospectively underwell-controlled laboratory conditions by studying 156 healthy, nonobesewomen (age 20-75 yr): 84 endurance-trained runners (ET) and 72 sedentary subjects (S). ET were matched across the age range forage-adjusted 10-km running performance. Body mass was positivelyrelated with age in S but not in ET. Fat-free mass was not differentwith age in ET or S. Maximal respiratory exchange ratio and rating ofperceived exertion were similar across age in ET and S, suggestingequivalent voluntary maximal efforts. There was a significant butmodest decline in running mileage, frequency, and speed with advancingage in ET.O_{2 max}(ml · kg¹ · min¹)was inversely related to age (P < 0.001) in ET (r = 0.82) and S(r = 0.71) and was higher atany age in ET. Consistent with our meta-analysic findings,the absolute rate of decline inO_{2 max} was greater inET (5.7ml · kg¹ · min¹ · decade¹)compared with S (3.2 ml · kg¹ · min¹ · decade¹;P < 0.01), but the relative (%)rate of decline was similar (9.7 vs 9.1%/decade; notsignificant). The greater absolute rate of decline inO_{2 max} in ET comparedwith S was not associated with a greater rate of decline in maximalheart rate (5.6 vs. 6.2beats · min¹ · decade¹),nor was it related to training factors. The present cross-sectional findings provide additional evidence that the absolute, but not therelative, rate of decline in maximal aerobic capacity with age may begreater in highly physically active women compared with theirsedentary healthy peers. This difference does not appear to be relatedto age-associated changes in maximal heart rate, bodycomposition, or training factors.

     

Muscle chemoreflex increases renal sympathetic nerve activity during exercise

O'Hagan, Kathleen P., Susan M. Casey, and Philip S. Clifford. Muscle chemoreflex increases renalsympathetic nerve activity during exercise. J. Appl.Physiol. 82(6): 1818-1825, 1997.Activation ofthe muscle chemoreflex increases sympathetic drive to skeletal musclein humans. This study investigated whether activation of the musclechemoreflex augments the renal sympathetic nerve activity (RSNA)response to dynamic exercise in rabbits. The muscle chemoreflex wasevoked by hindlimb ischemia during exercise on a motorized treadmill.Seven New Zealand White rabbits performed a nonischemic controlprotocol and a hindlimb ischemia protocol in which terminal aorticblood flow (ta) was reduced to 51 ± 2% ofpreocclusion ta by partial aortic occlusion after 1.5 min of exercise. Mean arterial pressure (MAP), heart rate, RSNA andta increased in response to exercise and weresimilar between trials during the first 1.5 min of exercise. In thecontrol trial, ta, MAP, and RSNA were stable at anelevated level through an additional 3.5 min of exercise. Hindlimbischemia produced a potent pressor response that plateaued after 2.5 min (+17 ± 4 mmHg, where  designates change). RSNA began toincrease after 1.5 min of ischemic exercise and was significantlyelevated relative to preocclusion RSNA at 2.5 (+25 ± 9%) and3.5 (+47 ± 12%) min of occlusion. These results suggest thatthe muscle chemoreflex can augment sympathoexcitatory drive to thekidney during dynamic exercise.

     

Analytic calculation of physiological acid-base parameters in plasma

Analytic expressions for plasma total titratablebase, base excess (C_B), strong-ion difference, changein strong-ion difference (SID), change in Van Slyke standardbicarbonate (VSSB), anion gap, and change in anion gap are derivedas a function of pH, total buffer ion concentration, and conditionalmolar equilibrium constants. The behavior of these various parametersunder respiratory and metabolic acid-base disturbances for constant andvariable buffer ion concentrations is considered. For constantnoncarbonate buffer concentrations, SID = C_B = VSSB, whereas these equalities no longer hold under changes innoncarbonate buffer concentration. The equivalence is restored if thereference state is changed to include the new buffer concentrations.

     

Interferon-gamma has immunomodulatory effects with minor endocrine and metabolic effects in humans

To evaluatewhether interferon- (IFN-) is involved in the interaction betweenthe immune and endocrine systems in vivo, we studied six healthysubjects twice in a placebo-controlled trial: once after administrationof recombinant human IFN- and, on another occasion, afteradministration of saline. The rate of appearance of glucose wasdetermined by infusion of[6,6-²H₂]glucoseand resting energy expenditure by indirect calorimetry. Human leukocyteantigen-DR gene expression on monocytes and serum neopterin increased after administration of IFN-(P < 0.05 vs. control). IFN-increased serum interleukin-6 levels significantly. Levels of tumornecrosis factor- remained below detection limits. IFN- increasedplasma concentrations of ACTH and cortisol(P < 0.05 vs. control), IFN- didnot alter concentrations of growth hormone,(nor)epinephrine, insulin, C peptide, glucagon, or insulin-like growthfactor I. IFN- did not alter plasma concentrations of glucose andfree fatty acids nor the rate of appearance of glucose. IFN-increased resting energy expenditure significantly. We conclude thatIFN- is a minor stimulator of the endocrine and metabolic pathways.Therefore, IFN- by itself is probably not a major mediator in theinteraction between the immune and the endocrine and metabolic systems.     

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.

     

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.

     

Absence of myofibrillar creatine kinase and diaphragm isometric function during repetitive activation

Creatine kinase(CK) provides ATP buffering in skeletal muscle and is expressed as1) cytosolic myofibrillar CK (M-CK)and 2) sarcomeric mitochondrial CK(ScCKmit) isoforms that differ in their subcellular localization. Wecompared the isometric contractile and fatigue properties of1) control CK-sufficient (Ctl),2) M-CK-deficient (M-CK[/]), and3) combined M-CK/ScCKmit-deficientnull mutant (CK[/]) diaphragm (Dia) todetermine the effect of the absence of M-CK activity on Dia performancein vitro. Baseline contractile properties were comparable across groupsexcept for specific force, which was ~16% lower inCK[/] Dia compared withM-CK[/] and Ctl Dia. During repetitiveactivation (40 Hz, duty cycle), force declined in all threegroups. This decline was significantly greater inCK[/] Dia compared with Ctl and M-CK[/] Dia. The pattern of forcedecline did not differ between M-CK[/] andCtl Dia. We conclude that Dia isometric muscle function is notabsolutely dependent on the presence of M-CK, whereas the completeabsence of CK acutely impairs isometric force generation duringrepetitive activation.