Effect of oxygen tension and rate of pressure reduction during decompression on central gas bubbles

Reinertsen, R. E., V. Flook, S. Koteng, and A. O. Brubakk.Effect of oxygen tension and rate of pressure reduction duringdecompression on central gas bubbles. J. Appl.Physiol. 84(1): 351-356, 1998.Reduction inascent speed and an increase in theO₂ tension in the inspired airhave been used to reduce the risk for decompression sickness. It haspreviously been reported that decompression speed andO₂ partial pressure are linearly related for human decompressions from saturation hyperbaric exposures. The constant of proportionality K(K = rate/partial pressure of inspiredO₂) indicates the incidence ofdecompression sickness. The present study investigated the relationshipamong decompression rate, partial pressure of inspiredO₂, and the number of central gasbubbles after a 3-h dive to 500 kPa while breathing nitrox with an O₂ content of 35 kPa. Weused transesophageal ultrasonic scanning to determine the number ofbubbles in the pulmonary artery of pigs. The results show that, for agiven level of decompression stress, decompression rate andO₂ tension in the inspired air canbe traded off against each other by using pulmonary artery bubbles asan end point. The results also seem to confirm that decompressions thathave a high K value are morestressful.

     

Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

Gelfand, R., C. J. Lambertsen, J. M. Clark, and E. Hopkin.Hypoxic ventilatory sensitivity in men is not reduced by prolongedhyperoxia (Predictive Studies V and VI). J. Appl.Physiol. 84(1): 292-302, 1998.Potential adverseeffects on the O₂-sensing functionof the carotid body when its cells are exposed to toxic O₂ pressures were assessed duringinvestigations of human organ tolerance to prolonged continuous andintermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxicventilatory responses (HVR) were determined at 1.0 ATA before and aftersevere hyperoxic exposures: 1)continuous O₂ breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and2) intermittentO₂ breathing at 2.0 ATA (30 minO₂-30 min normoxia) for 14.3 O₂ h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared withpreexposure controls. The hyperbolas were temporarily elevated tohigher ventilations than controls due to increments in respiratory frequency that were proportional toO₂ exposure time, notO₂ pressure. In humans, prolongedhyperoxia does not attenuate the hypoxia-sensing function of theperipheral chemoreceptors, even after exposures that approach limits ofhuman pulmonary and central nervous system O₂ tolerance. Current applicationsof hyperoxia in hyperbaric O₂therapy and in subsea- and aerospace-related operations are guided byand are well within these exposure limits.

     

In vivo assessment of changes in air and tissue volumes after pneumonectomy

Takeda, S., E. Y. Wu, R. H. Epstein, A. S. Estrera, and C. C. W. Hsia. In vivo assessment of changes in air and tissue volumes after pneumonectomy. J. Appl.Physiol. 82(4): 1340-1348, 1997.We examined theprogression and topographical distribution of postpneumonectomy volumechanges in immature foxhounds undergoing right pneumonectomy (R-Pnx,n = 5) or sham pneumonectomy (Sham, n = 6) at 2 mo of age and subsequentlyraised to maturity. Volumes of lung air (Vair) and tissue(Vti) were estimated by computerized tomography (CT) scan at 7, 22, and52 wk after surgery at a transpulmonary pressure of 20 cmH₂O. Estimates of Vti by CT scanincluded both septal tissue as well as nonseptal tissue (small- andmedium-sized airways and blood vessels); these were compared withestimates of septal Vti by an acetylene rebreathing (Rb) method. Wefound significant correlations between these techniques(Vair_CT = 0.83 Vair_Rb + 275, R = 0.97;Vti_CT = 1.62 Vti_Rb  30, R = 0.81). Extravascular septal Vtireturned to normal 7 wk after R-Pnx and remained normal up to maturity.Nonseptal Vti remained significantly below normal. The greatestincrease in Vti occurred in the midlung region just cephalad and caudalto the heart. After an early period of accelerated tissue growth afterR-Pnx, the rate of septal tissue growth matched that of somatic growth,whereas nonseptal tissue growth lagged behind. Compensatory growth ofthe remaining left lung was not associated with selectivealterations in thoracic development.

     

Regional intramuscular pressure development and fatigue in the canine gastrocnemius muscle in situ

Ameredes, Bill T., and Mark A. Provenzano. Regionalintramuscular pressure development and fatigue in the caninegastrocnemius muscle in situ. J. Appl.Physiol. 83(6): 1867-1876, 1997.Intramuscular pressure (P_IM) was measuredsimultaneously in zones of the medial head of thegastrocnemius-plantaris muscle group (zone I, popliteal origin; zoneII, central; zone III, near calcaneus tendon) to determine regionalmuscle mechanics during isometric tetanic contractions. PeakP_IM averages were 586, 1,676, and993 mmHg deep in zones I, II, and III and 170, 371, and 351 mmHgsuperficially in zones I, II, and III, respectively. During fatigue,loss of P_IM across zones wasgreatest in zone III (81%) and least in zone I (60%) when whole muscle tension loss was 49%. Recovery ofP_IM was greatest in zone III andleast in zone II, achieving 86% and 67% of initial P_IM, respectively, when tensionrecovered to 89%. These data demonstrate that1) regional mechanical performancecan be measured as P_IM within awhole muscle, 2)P_IM is nonuniform within thecanine gastrocnemius-plantaris muscle, being greatest in the deepcentral zone, and 3) fatigue andrecovery of P_IM are dissimilaracross regions. These differences suggest distinct local effects that integrate to determine whole muscle mechanical capacity during andafter intense exercise.

     

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

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

     

Effects of a synthetic lung surfactant on pharyngeal patency in awake human subjects

Van der Touw, T., A. B. H. Crawford, and J. R. Wheatley.Effects of a synthetic lung surfactant on pharyngeal patency inawake human subjects. J. Appl.Physiol. 82(1): 78-85, 1997.We examined theeffects of separate applications of saline and a synthetic lungsurfactant preparation (Surf; Exosurf Neonatal) into the supraglotticairway (SA) on the anteroposterior pharyngeal diameter(D_ap) and theairway pressures required to close (Pcl) and reopen (Pop) theSA in five awake normal supine subjects. D_ap, Pcl, and Popwere determined during lateral X-ray fluoroscopy and voluntary glotticclosure when pressure applied to the SA lumen was decreasedfrom 0 to 20 cmH₂O and thenincreased to +20 cmH₂O. After Surfapplication and relative to control,D_ap was largerfor most of the applied pressures, Pcl decreased (12.3 ± 1.9 to 18.7 ± 0.9 cmH₂O;P < 0.01), Pop decreased (13.4 ± 1.9 to 6.0 ± 3.4 cmH₂O;P < 0.01), and genioglossus electromyographic activity did not change (P > 0.05).Saline had no effect. These observations suggest that pharyngealintraluminal surface properties are important in maintaining pharyngealpatency. We propose that surfactants enhance pharyngeal patency byreducing surface tension and adhesive forces acting on intraluminal SAsurfaces.

     

A model for phosphocreatine resynthesis

Nevill, Alan M., David A. Jones, David McIntyre, Gregory C. Bogdanis, and Mary E. Nevill. A model forphosphocreatine resynthesis. J. Appl.Physiol. 82(1): 329-335, 1997.A model for phosphocreatine (PCr) resynthesis is proposed based on a simple electric circuit, where the PCr store in muscle is likened to thestored charge on the capacitor. The solution to the second-order differential equation that describes the potential around the circuitsuggests the model for PCr resynthesis is given byPCr(t) = R  [d₁ ^· exp(k₁ ^· t) ± d₂ ^· exp(k₂ ^· t)],where R is PCr concentration at rest,d₁,d₂, k₁, andk₂ are constants, andt is time. By using nonlinear leastsquares regression, this double-exponential model was shown to fit thePCr recovery data taken from two studies involving maximal exerciseaccurately. In study 1, when themuscle was electrically stimulated while occluded, PCr concentrations rose during the recovery phase to a level above that observed at rest.In study 2, after intensive dynamicexercise, PCr recovered monotonically to resting concentrations. Thesecond exponential term in the double-exponential model was found tomake a significant additional contribution to the quality of fit inboth study 1 (P < 0.05) andstudy 2 (P < 0.01).

     

Optical measurement of isolated canine lung filtration coefficients at normal hematocrits

Klaesner, Joseph W., N. Adrienne Pou, Richard E. Parker,Charlene Finney, and Robert J. Roselli. Optical measurement ofisolated canine lung filtration coefficients at normal hematocrits. J. Appl. Physiol. 83(6):1976-1985, 1997.In this study, lung filtration coefficient(K_fc) valueswere measured in eight isolated canine lung preparations at normalhematocrit values using three methods: gravimetric, blood-correctedgravimetric, and optical. The lungs were kept in zone 3 conditions andsubjected to an average venous pressure increase of 10.24 ± 0.27 (SE) cmH₂O. The resulting K_fc(ml · min¹ · cmH₂O¹ · 100 g dry lung wt¹) measuredwith the gravimetric technique was 0.420 ± 0.017, which wasstatistically different from theK_fc measured bythe blood-corrected gravimetric method (0.273 ± 0.018) or theproduct of the reflection coefficient(_f) andK_fc measuredoptically (0.272 ± 0.018). The optical method involved the use of aCellco filter cartridge to separate red blood cells from plasma, whichallowed measurement of the concentration of the tracer in plasma atnormal hematocrits (34 ± 1.5). The permeability-surface areaproduct was measured using radioactive multiple indicator-dilutionmethods before, during, and after venous pressure elevations. Resultsshowed that the surface area of the lung did not change significantlyduring the measurement ofK_fc. Thesestudies suggest that_fK_fccan be measured optically at normal hematocrits, that this measurement is not influenced by blood volume changes that occur during the measurement, and that the optical_fK_fcagrees with theK_fc obtained viathe blood-corrected gravimetric method.

     

Human ventilatory response to acute hyperoxia during and after 8h of both isocapnic and poikilocapnic hypoxia

Tansley, J. G., C. Clar, M. E. F. Pedersen, and P. A. Robbins. Human ventilatory response to acute hyperoxia during andafter 8 h of both isocapnic and poikilocapnic hypoxia.J. Appl. Physiol. 82(2): 513-519, 1997.During 8 h of either isocapnic or poikilocapnic hypoxia,there may be a rise in ventilation(E) thatcannot be rapidly reversed with a return to higherPO₂ (L. S. G. E. Howard and P. A. Robbins. J. Appl. Physiol. 78:1098-1107, 1995). To investigate this further, threeprotocols were compared: 1) 8-hisocapnic hypoxia [end-tidalPCO₂(PET_CO2 ) held atprestudy value, end-tidal PO₂(PET_O2) = 55 Torr],followed by 8-h isocapnic euoxia(PET_O2 = 100 Torr);2) 8-h poikilocapnic hypoxia followed by 8-h poikilocapnic euoxia; and3) 16-h air-breathing control.Before and at intervals throughout each protocol, theE response to eucapnichyperoxia (PET_CO2 held1-2 Torr above prestudy value,PET_O2 = 300 Torr) wasdetermined. There was a significant rise in hyperoxic E over 8 hduring both forms of hypoxia (P < 0.05, analysis of variance) that persisted during the subsequent 8-heuoxic period (P < 0.05, analysis ofvariance). These results support the notion that an 8-h period ofhypoxia increases subsequenthyperoxic E, even if acid-base changes have been minimized through maintenance ofisocapnia during the hypoxic period.

     

Oxygen pulse in guinea pigs in hyperbaric helium and hydrogen

Kayar, Susan R., and Erich C. Parker. Oxygen pulse inguinea pigs in hyperbaric helium and hydrogen. J. Appl. Physiol. 82(3): 988-997, 1997.We analyzedO₂ pulse, the total volume of O₂ consumed per heart beat, inguinea pigs at pressures from 10 to 60 atmospheres. Animals were placedin a hyperbaric chamber and breathed 2%O₂ in either helium (heliox) orhydrogen (hydrox). Oxygen consumption rate(O₂) was measured by gaschromatographic analysis. Core temperature and heart rate were measuredby using surgically implanted radiotelemeters. TheO₂ was modulated over afourfold range by varying chamber temperature from 25 to 36°C. There was a direct correlation betweenO₂ and heartrate, which was significantly different for animals in heliox vs.hydrox (P = 0.003). By usingmultivariate regression analysis, we identified variables that weresignificant to O₂ pulse: bodysurface area, chamber temperature, core temperature, and pressure.After normalizing for all nonpressure variables, the residualO₂ pulse was found to decreasesignificantly (P = 0.02) with pressurefor animals in heliox but did not decrease significantly(P = 0.38) with pressure for animalsin hydrox over the range of pressures studied. This amounted to aroughly 25% lower O₂ pulse fornormothermic animals in 60 atmospheres heliox vs. hydrox. These resultssuggest that reduction of cardiovascular efficiency in a hyperbaricenvironment can be mitigated by the choice of breathing gas.

     

Letters to the Editor

The following are the abstracts of the articles discussed inthe subsequent letter:

  Huang, Yuh-Chin T., Aneysa C. Sane, Steven G. Simonson, Thomas A. Fawcett, Richard E. Moon,Philip J. Fracica, Margaret G. Menache, Claude A. Piantadosi, andStephen L. Young. Artificial surfactant attenuates hyperoxic lunginjury in primates. I. Physiology and biochemistry. J. Appl.Physiol. 78(5): 1816-1822, 1995.Prolonged exposure toO₂ causes diffuse alveolar damage and surfactantdysfunction that contribute to the pathophysiology of hyperoxic lunginjury. We hypothesized that exogenous surfactant would improve lungfunction during O₂ exposure in primates. Sixteen healthymale baboons (10-15 kg) were anesthetized and mechanically ventilated for 96 h. The animals received either 100% O₂(n = 6) or 100% O₂ plus aerosolized artificialsurfactant (Exosurf; n = 5). A third group of animals(n = 5) was ventilated with an inspired fraction ofO₂ of 0.21 to control for the effects of sedation andmechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion distribution(_A/) was measureddaily using a multiple inert-gas elimination technique. Positive end-expiratory pressure was kept at 2.5 cmH₂O andwas intermittently raised to 10 cmH₂O for 30 minto obtain additional measurements of_A/. After theexperiments, lungs were obtained for biochemical and histologicalassessment of injury. O₂ exposures altered hemodynamics,progressively worsened_A/, altered lung phospholipid composition, and produced severe lung edema. Artificial surfactant therapy significantly increased disaturatedphosphatidylcholine in lavage fluid and improved intrapulmonary shunt,arterial PO₂, and lung edema. Surfactant alsoenhanced the shunt-reducing effect of positive end-expiratory pressure.We conclude that an aerosolized protein-free surfactant decreased theprogression of pulmonary O₂ toxicity in baboons.

     

"Living high-training low": effect of moderate-altitude acclimatization with low-altitude training on performance

Levine, Benjamin D., and James Stray-Gundersen."Living high-training low": effect of moderate-altitudeacclimatization with low-altitude training on performance.J. Appl. Physiol. 83(1): 102-112, 1997.The principal objective of this study was to test the hypothesisthat acclimatization to moderate altitude (2,500 m) plus training atlow altitude (1,250 m), "living high-training low," improvessea-level performance in well-trained runners more than an equivalentsea-level or altitude control. Thirty-nine competitive runners (27 men,12 women) completed 1) a 2-wklead-in phase, followed by 2) 4 wkof supervised training at sea level; and3) 4 wk of field training camprandomized to three groups: "high-low"(n = 13), living at moderate altitude(2,500 m) and training at low altitude (1,250 m); "high-high"(n = 13), living and training atmoderate altitude (2,500 m); or "low-low"(n = 13), living and training in amountain environment at sea level (150 m). A 5,000-m time trial was theprimary measure of performance; laboratory outcomes included maximalO₂ uptake(O_{2 max}), anaerobic capacity (accumulated O₂ deficit),maximal steady state (MSS; ventilatory threshold), running economy,velocity at O_{2 max}, and blood compartment volumes. Both altitude groups significantly increased O_{2 max}(5%) in direct proportion to an increase in red cell mass volume(9%; r = 0.37, P < 0.05), neither of which changedin the control. Five-kilometer time was improved by the field trainingcamp only in the high-low group (13.4 ± 10 s), in directproportion to the increase inO_{2 max}(r = 0.65, P < 0.01). Velocity atO_{2 max} andMSS also improved only in the high-low group. Four weeks of livinghigh-training low improves sea-level running performance in trainedrunners due to altitude acclimatization (increase in red cell massvolume and O_{2 max}) and maintenance of sea-level training velocities, mostlikely accounting for the increase in velocity atO_{2 max} and MSS.

     

Resistance and aerobic training in older men: effects on VO2 peak and the capillary supply to skeletal muscle

Hepple, R. T., S. L. M. Mackinnon, J. M. Goodman, S. G. Thomas, and M. J. Plyley. Resistance and aerobic training in oldermen: effects onO_{2 peak} and thecapillary supply to skeletal muscle. J. Appl.Physiol. 82(4): 1305-1310, 1997.Both aerobic training (AT) and resistance training (RT) may increase aerobic power(O_{2 peak}) in theolder population; however, the role of changes in the capillary supplyin this response has not been evaluated. Twenty healthymen (age 65-74 yr) engaged in either 9 wk of lower body RTfollowed by 9 wk of AT on a cycle ergometer (RTAT group) or 18 wk of AT on a cycle ergometer (ATAT group). RT was performedthree times per week and consisted of three sets of four exercises at6-12 repetitions maximum. AT was performed threetimes per week for 30 min at 60-70% heart ratereserve. O_{2 peak} was increasedafter both RT and AT (P < 0.05).Biopsies (vastus lateralis) revealed that the number of capillaries per fiber perimeter length was increased after both AT and RT(P < 0.05), paralleling the changesin O_{2 peak}, whereascapillary density was increased only after AT(P < 0.01). These results, and thefinding of a significant correlation between the change in capillarysupply and O_{2 peak}(r = 0.52), suggest the possibility that similar mechanisms may be involved in the increase ofO_{2 peak} afterhigh-intensity RT and AT in the older population.

     

Letters to the Editor

The following is the abstract of the article discussed in thesubsequent letter:

Verbanck, S., D. Schuermans, A. Van Muylem, M. Paiva, M. Noppen, and W. Vincken. Ventilation distribution duringhistamine provocation. J. Appl. Physiol.83(6):1907-1916, 1997.We investigated ventilation inhomogeneityduring provocation with inhaled histamine in 20 asymptomatic nonsmokingsubjects. We used N₂ multiple-breath washout (MBW) toderive parameters S_cond andS_acin as a measurement of ventilationinhomogeneity in conductive and acinar zones of the lungs,respectively. A 20% decrease of forced expiratory volume in 1 s(FEV₁) was used to distinguish responders fromnonresponders. In the responder group, average FEV₁decreased by 26%, whereas S_cond increased by390% with no significant change in S_acin. In the nonresponder group, FEV₁ decreased by 11%, whereasS_cond increased by 198% with no significantS_acin change. Despite the absence of change inS_acin during provocation, baselineS_acin was significantly larger in the respondervs. the nonresponder group. The main findings of our study are thatduring provocation large ventilation inhomogeneities occur, that thesmall airways affected by the provocation process are situated proximalto the acinar zone where the diffusion front stands, and that, inaddition to overall decrease in airway caliber, there is inhomogeneousnarrowing of parallel airways.

     

Effects of blue light deficiency on acclimation of light energy partitioning in PSII and CO2 assimilation capacity to high irradiance in spinach leaves

Blue light effects on the acclimation of energy partitioningcharacteristics in PSII and CO₂ assimilation capacity in spinachto high growth irradiance were investigated. Plants were grownhydroponically in different light treatments that were a combinationof two light qualities and two irradiances, i.e. white lightand blue-deficient light at photosynthetic photon flux densities(PPFDs) of 100 and 500 µmol m^–2 s^–1. The CO₂assimilation rate, the quantum efficiency of PSII (PSII) andthermal dissipation activity / in young, fully expanded leaves were measured under 1,600 µmol m^–2 s^–1white light. The CO₂ assimilation rate and PSII were higher,while / was lower in plants grown under high irradiancethan in plants grown under low irradiance. These responses wereobserved irrespective of the presence or absence of blue lightduring growth. The extent of the increase in the CO₂ assimilationrate and PSII and the decrease in / by high growth irradiance was smaller under blue light-deficient conditions. These resultsindicate that blue light helps to boost the acclimation responsesof energy partitioning in PSII and CO₂ assimilation to highirradiance. Similarly, leaf N, Cyt f and Chl contents per unitleaf area increased by high growth irradiance, and the extentof the increment in leaf N, Cyt f and Chl was smaller underblue light-deficient conditions. Regression analysis showedthat the differences in energy partitioning in PSII and CO₂assimilation between plants grown under high white light andhigh blue-deficient light were closely related to the differencein leaf N.     

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

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

     

Longitudinal distribution of O3 absorption in the lung: gender differences and intersubject variability

Bush, Michele L., Patrick T. Asplund, Kristen A. Miles,Abdellaziz Ben-Jebria, and James S. Ultman. Longitudinaldistribution of O₃ absorption inthe lung: gender differences and intersubject variability.J. Appl. Physiol. 81(4):1651-1657, 1996.Because the National Ambient Air QualityStandard for ozone (O₃) isintended to protect the most sensitive individuals in the generalpopulation, it is necessary to identify sources of intersubjectvariation in the exposure-dose-response cascade. We hypothesize thatdifferences in lung anatomy can modulate exposure-dose relationshipsbetween individuals, and this results in differences between theirresponsiveness to O₃ at a fixedexposure condition. During quiet breathing, the conducting airwaysremove the majority of inhaled O₃,so the volume of this region should have an important impact onO₃ dose distribution. Employingthe bolus inhalation method, we measured the distribution ofO₃ absorption with respect topenetration volume (V_P), and using the Fowler single-breath N₂washout method, we determined the dead space volume(VD) in the lungs of 10 menand 10 women at a fixed respiratory flow of 250 ml/s. On average, thewomen absorbed O₃ at smallerV_P than the men, and the women hadsmaller VD than the men. Whenexpressed in terms ofV_P/ VD,the absorption distribution of the men and women was indistinguishable.Moreover, an interpretation of theO₃ distribution in terms of anintrinsic mass transfer parameter(Ka) indicated that differencesbetween the O₃ dosimetry in allsubjects, whether men or women, could be explained by a uniquecorrelation with anatomic dead space: Ka (ins¹) = 610 VD^1.05(in ml). Application of this result to measurements ofO₃ exposure response indicatedthat previously reported gender differences may be due to a failure inproperly accounting for tissue surface within the conducting airways.

     

High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma

Berg, John T., Zhenxing Fu, Ellen C. Breen, Hung-Cuong Tran,Odile Mathieu-Costello, and John B. West. High lung inflation increases mRNA levels of ECM components and growth factors in lungparenchyma. J. Appl. Physiol. 83(1):120-128, 1997.Remodeling of pulmonary capillaries occurs afterchronic increases in capillary pressure (e.g., mitral stenosis). Also,remodeling of pulmonary arteries begins within 4 h of increased wallstress and is endothelium dependent. We have previously shown that highlung inflation increases wall stress in pulmonary capillaries. Thisstudy was designed to determine whether high lung inflation inducesremodeling of the extracellular matrix (ECM) in lung parenchyma.Open-chest rabbits were ventilated for 4 h with9-cmH₂O positive end-expiratory pressure (PEEP) on one lung and1-cmH₂O PEEP on the other(High-PEEP group), or with 2-cmH₂OPEEP on both lungs (Low-PEEP group). An additional untreated controlgroup was also included. We found increased levels of mRNA in bothlungs of High-PEEP rabbits (compared with both the Low-PEEP anduntreated groups) for ₁(III)and ₂(IV) procollagen,fibronectin, basic fibroblast growth factor, and transforming growthfactor-₁. In contrast,₂(I) procollagen and vascularendothelial growth factor mRNA levels were not changed. We concludethat high lung inflation for 4 h increases mRNA levels of ECMcomponents and growth factors in lung parenchyma.

     

Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method

Kim, Chong S., S. C. Hu, P. DeWitt, and T. R. Gerrity.Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method. J. Appl.Physiol. 81(5): 2203-2213, 1996.Detailedregional deposition of inhaled particles was investigated in youngadults (n = 11) by use of aserial bolus aerosol delivery technique. A small bolus (45 mlhalf-width) of monodisperse aerosols [1-, 3-, and5-µm particle diameter(D_p)] wasdelivered sequentially to a specific volumetric depth of the lung(100-500 ml in 50-ml increments), while the subject inhaled cleanair via a laser aerosol photometer (25-ml dead volume) with a constantflow rate ( = 150, 250, and 500 ml/s) andexhaled with the same without a pause to theresidual volume. Deposition efficiency (LDE) and deposition fraction in10 local volumetric regions and total deposition fraction of the lungwere obtained. LDE increased monotonically with increasing lung depthfor all three D_p.LDE was greater with smaller values in all lungregions. Deposition was distributed fairly evenly throughout the lungregions with a tendency for an enhancement in the distal lung regions for D_p = 1 µm.Deposition distribution was highly uneven forD_p = 3 and 5 µm, and the region of the peak deposition shifted toward the proximalregions with increasingD_p. Surface dosewas 1-5 times greater in the small airway regions and 2-17times greater in the large airway regions than in the alveolar regions.The results suggest that local or regional enhancement of deposition occurs in healthy subjects and that the local enhancement can be animportant factor in health risk assessment of inhaled particles.

     

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 .