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.

     

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.

     

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.     

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.

     

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.

     

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.

     

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.

     

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.

     

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.

     

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).

     

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.

     

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 .

     

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.

     

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.

     

A model for the regulation of cerebral oxygen delivery

On the basis of the assumption that oxygen delivery across theendothelium is proportional to capillary plasmaPO₂, a model is presented that linkscerebral metabolic rate of oxygen utilization(CMR_O2) to cerebral blood flow(CBF) through an effective diffusivity for oxygen (D) of the capillarybed. On the basis of in vivo evidence that the oxygen diffusivityproperties of the capillary bed may be altered by changes in capillaryPO₂, hematocrit, and/or bloodvolume, the model allows changes in D with changes in CBF. Choice inthe model of the appropriate ratio of   (D/D)/(CBF/CBF)determines the dependence of tissue oxygen delivery on perfusion.Buxton and Frank (J. Cereb. Blood Flow. Metab. 17: 64-72, 1997) recently presented alimiting case of the present model in which  = 0. In contrast to thetrends predicted by the model of Buxton and Frank, in the current modelwhen > 0, the proportionality between changes in CBF andCMR_O2 becomes more linear, and similardegrees of proportionality can exist at different basal values ofoxygen extraction fraction. The model is able to fit the observedproportionalities between CBF and CMR_O2 for a large range ofphysiological data. Although the model does not validate any particularobserved proportionality between CBF andCMR_O2, generally values of(CMR_O2/CMR_O2)/(CBF/CBF) close to unity have been observed across ranges of graded anesthesia inrats and humans and for particular functional activations in humans.The model's capacity to fit the wide range of data indicates that theoxygen diffusivity properties of the capillary bed, which can bemodified in relation to perfusion, play an important role in regulatingcerebral oxygen delivery in vivo.

     

Age, fitness, and regional blood flow during exercise in the heat

Ho, C. W., J. L. Beard, P. A. Farrell, C. T. Minson, and W. L. Kenney. Age, fitness, and regional blood flow during exercisein the heat. J. Appl. Physiol. 82(4):1126-1135, 1997.During dynamic exercise in warm environments,the requisite increase in skin blood flow (SkBF) is supported by anincrease in cardiac output (c) and decreases insplanchnic (SBF) and renal blood flows (RBF). To examine interactionsbetween age and fitness in determining this integrated response, 24 men, i.e., 6 younger fit (YF), 6 younger sedentary (YS), 6 older fit (OF), and 6 older sedentary (OS) rested for 50 min, thenexercised at 35 and 60% maximalO₂ consumption(O_{2 max}) at36°C ambient temperature. YF had a significantly higherc and SkBF than any other group during exercise,but fitness level had no significant effect on any measured variable inthe older men. At 60%O_{2 max}, younger subjects had significantly greater decreases in SBF and RBF than theolder men, regardless of fitness level. Total flow redirected fromthese two vascular beds (SBF + RBF) followed YF >> YS > OF > OS. A rigorous 4-wk endurance training programincreased exercise SkBF in OS, but SBF and RBF were unchanged.Under these conditions, older men distribute cdifferently to regional circulations, i.e., smaller increases in SkBFand smaller decreases in SBF and RBF. In younger subjects, the higherSkBF associated with a higher fitness level is a function of both ahigher c and a greater redistribution of flow fromsplanchnic and renal circulations, but the attenuated splanchnic andrenal vasoconstriction in older men does not appear to change withenhanced aerobic fitness.

     

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.

     

Dynamic resistance exercise and resting blood pressure in adults: a meta-analysis

George, Kelley. Dynamic resistance exercise and restingblood pressure in adults: a meta-analysis. J. Appl.Physiol. 82(5): 1559-1565, 1997.With the use ofthe meta-analytic approach, the purpose of this study was to examinethe effects of dynamic resistance exercise, i.e., weight training, onresting systolic and diastolic blood pressure in adults. A total ofnine studies consisting of 259 subjects (144 exercise, 115 control) and18 groups (9 exercise, 9 control) were included in this analysis. Withthe use of the bootstrap technique (10,000 samples), significant treatment effect(₃)reductions were found across all designs and categories for bothsystolic and diastolic blood pressure [systolic, mean ± SD = 4.55 ± 1.75 mmHg, 95% confidence interval (CI) = 1.56 to 8.56; diastolic, mean ± SD = 3.79 + 1.12 mmHg, 95% confidence interval CI = 1.89 to6.33]. ₃ changescorresponded with relative decreases of ~3 and 4% in restingsystolic and diastolic blood pressure, respectively. Inconclusion, meta-analytic review of included studies suggests thatdynamic resistance exercise reduces resting systolic and diastolicblood pressure in adults. However, it is premature to form strongconclusions regarding the effects of dynamic resistance exercise onresting blood pressure. A need exists for additional, well-designedstudies on this topic before a recommendation can be made regarding theefficacy of dynamic resistance exercise as a nonpharmacological therapyfor reducing resting blood pressure in adults, especially inhypertensive adults.

     

Kinetics of oxygen uptake at the onset of exercise in boys and men

The objective of this study was to compare theO₂ uptake(O₂) kinetics at the onsetof heavy exercise in boys and men. Nine boys, aged 9-12 yr, and 8 men, aged 19-27 yr, performed a continuous incremental cyclingtask to determine peak O₂(O_{2 peak}).On 2 other days, subjects performed each day four cycling tasks at 80 rpm, each consisting of 2 min of unloaded cycling followed twice bycycling at 50%O_{2 peak} for 3.5 min,once by cycling at 100%O_{2 peak} for 2 min,and once by cycling at 130%O_{2 peak} for 75 s.O₂ deficit was not significantlydifferent between boys and men (respectively, 50%O_{2 peak} task: 6.6 ± 11.1 vs. 5.5 ± 7.3 ml · min¹ · kg¹;100% O_{2 peak} task:28.5 ± 8.1 vs. 31.8 ± 6.3 ml · min¹ · kg¹;and 130%O_{2 peak}task: 30.1 ± 5.7 vs. 35.8 ± 5.3 ml · min¹ · kg¹).To assess the kinetics, phase I was excluded from analysis. Phase IIO₂ kinetics could bedescribed in all cases by a monoexponential function. ANOVA revealed nodifferences in time constants between boys and men (respectively, 50%O_{2 peak}task: 22.8 ± 5.1 vs. 26.4 ± 4.1 s; 100%O_{2 peak} task: 28.0 ± 6.0 vs. 28.1 ± 4.4 s; and 130%O_{2 peak} task: 19.8 ± 4.1 vs. 20.7 ± 5.7 s). In conclusion, O₂ deficit and fast-componentO₂ on-transientsare similar in boys and men, even at high exercise intensities, whichis in contrast to the findings of other studies employing simplermethods of analysis. The previous interpretation that children relyless on nonoxidative energy pathways at the onset of heavy exercise isnot supported by our findings.

     

Influence of age and gender on cardiac output-VO2 relationships during submaximal cycle ergometry

Proctor, David N., Kenneth C. Beck, Peter H. Shen, Tamara J. Eickhoff, John R. Halliwill, and Michael J. Joyner. Influence ofage and gender on cardiacoutput-O₂ relationshipsduring submaximal cycle ergometry. J. Appl.Physiol. 84(2): 599-605, 1998.It is presentlyunclear how gender, aging, and physical activity status interact todetermine the magnitude of the rise in cardiac output(c) during dynamic exercise. To clarify this issue,the present study examined thec-O₂ uptake(O₂) relationship duringgraded leg cycle ergometry in 30 chronically endurance-trained subjects from four groups (n = 6-8/group): younger men (20-30 yr), older men (56-72yr), younger women (24-31 yr), and older women(51-72 yr). c (acetylene rebreathing), strokevolume (c/heart rate), and whole bodyO₂ were measured at restand during submaximal exercise intensities (40, 70, and ~90% of peakO₂). Baseline restinglevels of c were 0.6-1.2 l/min less in theolder groups. However, the slopes of thec-O₂relationship across submaximal levels of cycling were similar among allfour groups (5.4-5.9 l/l). The absolute cassociated with a given O₂(1.0-2.0 l/min) was also similar among groups. Resting andexercise stroke volumes (ml/beat) were lower in women than in men butdid not differ among age groups. However, older men and women showed areduced ability, relative to their younger counterparts, to maintainstroke volume at exercise intensities above 70% of peakO₂. This latter effect wasmost prominent in the oldest women. These findings suggest that neitherage nor gender has a significant impact on thec-O₂ relationships during submaximal cycle ergometry among chronically endurance-trained individuals.