Partitioning of airway and respiratory tissue mechanical impedances by body plethysmography

Peslin, R., and C. Duvivier. Partitioning of airway andrespiratory tissue mechanical impedances by body plethysmography. J. Appl. Physiol. 84(2): 553-561, 1998.We have tested the feasibility of separating the airway (Zaw)and tissue (Zti) components of total respiratory input impedance(Zrs,in) in healthy subjects by measuring alveolar gas compression bybody plethysmography (Vpl) during pressure oscillations at the airwayopening. The forced oscillation setup was placed inside a bodyplethysmograph, and the subjects rebreathedBTPS gas. Zrs,in and the relationship between Vpl and airway flow (Hpl) were measured from 4 to 29 Hz. Zawand Zti were computed from Zrs,in and Hpl by using the monoalveolar T-network model and alveolar gas compliance derived from thoracic gasvolume. The data were in good agreement with previous observations: airway and tissue resistance exhibited some positive and negative frequency dependences, respectively; airway reactance was consistent with an inertance of 0.015 ± 0.003 hPa · s² · l¹and tissue reactance with an elastance of 36 ± 8 hPa/l. The changes seen with varying lung volume, during elastic loading of the chest andduring bronchoconstriction, were mostly in agreement with the expectedeffects. The data, as well as computer simulation, suggest that thepartitioning is unaffected by mechanical inhomogeneity and onlymoderately affected by airway wall shunting.

     

Effect of expiratory flow limitation on respiratory mechanical impedance: a model study

Peslin, R., R. Farré, M. Rotger, and D. Navajas.Effect of expiratory flow limitation on respiratory mechanicalimpedance: a model study. J. Appl.Physiol. 81(6): 2399-2406, 1996.Large phasicvariations of respiratory mechanical impedance (Zrs) have been observedduring induced expiratory flow limitation (EFL) (M. Vassiliou, R. Peslin, C. Saunier, and C. Duvivier. Eur. Respir. J. 9: 779-786, 1996). To clarify themeaning of Zrs during EFL, we have measured from 5 to 30 Hz the inputimpedance (Zin) of mechanical analogues of the respiratory system,including flow-limiting elements (FLE) made of easily collapsiblerubber tubing. The pressures upstream (Pus) and downstream (Pds) fromthe FLE were controlled and systematically varied. Maximal flow(max) increased linearly with Pus, was close to thevalue predicted from wave-speed theory, and was obtained for Pus-Pds of4-6 hPa. The real part of Zin started increasing abruptlywith flow () >85%max and either further increased or suddenlydecreased in the vicinity of max. The imaginary part of Zin decreased markedly and suddenly above 95%max. Similar variations of Zin during EFL were seenwith an analogue that mimicked the changes of airwaytransmural pressure during breathing. After pressure and measurements upstream and downstream from the FLEwere combined, the latter was analyzed in terms of a serial (Zs) and ashunt (Zp) compartment. Zs was consistent with a large resistance andinertance, and Zp with a mainly elastic element having an elastanceclose to that of the tube walls. We conclude that Zrs data during EFLmainly reflect the properties of the FLE.

     

Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion

Simon, Brett A., Koichi Tsuzaki, and Jose G. Venegas.Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion. J. Appl.Physiol. 82(3): 882-891, 1997.Regionalpneumoconstriction induced by alveolar hypocapnia is an importanthomeostatic mechanism for optimization of ventilation-perfusionmatching. We used positron imaging of ¹³NN-equilibrated lungs to measurethe distribution of regional tidal volume(VT), lung volume(VL), and lung impedance(Z) before and after left (L)pulmonary artery occlusion (PAO) in eight anesthetized, open-chestdogs. Measurements were made during eucapnic sinusoidal ventilation at0.2 Hz with 4-cmH₂O positive end expiratory pressure. Right(R) and L lung impedances(ZRandZL)were determined from carinal pressure and positron imaging of dynamicregional VL. LPAO caused anincrease in|ZL|relative to|ZR|,resulting in a shift in VT awayfrom the PAO side, with a L/R|Z| ratio changing from 1.20 ± 0.07 (mean ± SE) to 2.79 ± 0.85 after LPAO(P < 0.05). Although mean L lungVL decreased slightly, theVL normalized parametersspecific admittance and specific compliance both significantly decreased with PAO. Lung recoil pressure at 50% totallung capacity also increased after PAO. We conclude that PAO results inan increase in regional lung Z thatshifts ventilation away from the affected area at normal breathingfrequencies and that this effect is not due to a change inVL but reflects mechanicalconstriction at the tissue level.

     

Evaluation of a forced oscillation method to measure thoracic gas volume

The purposeof this study was to test a plethysmographic method of measuringthoracic gas volume (TGV) that, contrary to the usual panting method,would not require any active cooperation from the subject. It is basedon the assumption that the out-of-phase component of airway impedancevaries linearly with frequency. By using that assumption, TGV may becomputed by combining measurements of total respiratory impedance (Zrs)and of the relationship between the plethysmographic signal (Vpl) andairway flow () during forcedoscillations at several frequencies. Zrs and Vpl/were measured at 10 noninteger multiple frequencies ranging from 4 to29 Hz in 15 subjects breathing gas in nearlyBTPS conditions. Forced oscillationmeasurements were immediately followed by determination of TGV by thestandard method. The data were analyzed on different frequency ranges,and the best agreement was seen in the 6- to 29-Hz range. Within thatrange, forced oscillation TGV and standard TGV differed little(3.92 ± 0.66 vs. 3.83 ± 0.73 liters,n = 77, P < 0.05) and were stronglycorrelated (r = 0.875); thedifferences were not correlated to the mean of the two estimates, andtheir SD was 0.35 liter. In seven subjects the differences weresignificantly different from zero, which may, in part, be due toimperfect gas conditioning. We conclude that the method is not highlyaccurate but could prove useful when, for lack of sufficientcooperation, the panting method cannot be used. The results of computersimulation, however, suggest that the method would be unreliable in thepresence of severe airway inhomogeneity or peripheral airwayobstruction.

     

Determination of airway and tissue resistances after antigen and methacholine in nonhuman primates

Madwed, Jeffrey B., and Andrew C. Jackson.Determination of airway and tissue resistances after antigen andmethacholine in nonhuman primates. J. Appl.Physiol. 83(5): 1690-1696, 1997.Antigen challenge of Ascaris suum-sensitiveanimals has been used as a model of asthma in humans. However, noreports have separated total respiratory resistance into airway (Raw)and tissue (Rti) components. We compared input impedance (Zin) andtransfer impedance (Ztr) to determine Raw and Rti in anesthetizedcynomolgus monkeys under control and bronchoconstricted conditions. Zindata between 1 and 64 Hz are frequency dependent during baselineconditions, and this frequency dependence shifts in response toA. suum or methacholine. Thus itcannot be modeled with the DuBois model, and estimates of Raw and Rticannot be determined. With Ztr, baseline data were much less variablethan Zin in all monkeys. After bronchial challenge withA. suum or methacholine, the absoluteamplitude of the resistive component of Ztr increased and its zerocrossing shifted to higher frequencies. These data can estimate Raw and Rti with the six-element DuBois model. Therefore, in monkeys, Ztr hasadvantages over other measures of lung function, since it provides amethodology to separate estimates of Raw and Rti. In conclusion, Ztrshows spectral features similar to those reported in healthy andasthmatic humans.

     

Human respiratory input impedance between 32and 800Hz, measured by interrupter technique and forced oscillations

Frey, Urs, Bela Suki, Richard Kraemer, and Andrew C. Jackson. Human respiratory input impedance between 32 and 800 Hz,measured by interrupter technique and forced oscillations. J. Appl. Physiol. 82(3):1018-1023, 1997.Respiratory input impedance (Zin) over a widerange of frequencies (f) has beenshown to be useful in determining airway resistance (Raw) and tissueresistance in dogs or airway wall properties in human adults. Zinmeasurements are noninvasive and, therefore, potentially useful ininvestigation of airway mechanics in infants. However, accuratemeasurements of Zin at these f valueswith the use of forced oscillatory techniques (FOT) in infants aredifficult because of their relatively high Raw and large compliance ofthe face mask. If pseudorandom noise pressure oscillations generated bya loudspeaker are applied at the airway opening (FOT), the power of theresulting flow decreases inversely withf because of capacitive shunting intothe volume of the gas in the speaker chamber and in the face mask. Westudied whether high-frequency respiratory Zin can be measured by using rapid flow interruption [high-speed interrupter technique(HIT)], in which we expect the flow amplitude in the respiratorysystem to be higher than in the FOT. We compared Zin measured by HIT with Zin measured by FOT in a dried dog lung and in five healthy adultsubjects. The impedance was calculated from two pressure signalsmeasured between the mouth and the HIT valve. The impedance could beassessed from 32 to 800 Hz. Its real part at lowf as well as thef and amplitude of the first andsecond acoustic resonance, measured by FOT and by HIT, were notsignificantly different. The power spectrum of oscillatory flow whenthe HIT was used showed amplitudes that were at least 100 times greaterthan those when FOT was used, increasing atf > 400 Hz. In conclusion,the HIT enables the measurement of high-frequency Zin data ranging from 32 to 800 Hz with particularly high flow amplitudes and, therefore, possibly better signal-to-noise ratio. This is particularly important in systems with high Raw, e.g., in infants, when measurements have tobe performed through a face mask.

     

Respiratory transfer impedance between 8and 384Hz in guinea pigs before and after bronchial challenge

Sobh, Jamil F., Craig M. Lilly, Jeffrey M. Drazen, andAndrew C. Jackson. Respiratory transfer impedance between 8 and384 Hz in guinea pigs before and after bronchial challenge. J. Appl. Physiol. 82(1): 172-181, 1997.We report a forced oscillatory technique for noninvasivelymeasuring respiratory transfer impedance (Ztr) between 8 and 384 Hz inguinea pigs. This technique uses a device consisting of two chambers:one surrounding the animal's head that is used as a plethysmograph tomeasured flow through the airway opening and the other that surroundsthe animal's body and is used to apply pressure oscillations to thebody surface. Ztr was measured in spontaneously breathing awake guineapigs and while the animals were anesthetized in normal andmethacholine-challenged conditions. An eight-element model consistingof an airway compartment separated from a tissue compartment by a shuntgas compression compartment was fit to the data. Anesthesia increasedcentral and peripheral airway resistance and bronchial airway wallcompliance by 13, 31, and 44%, respectively, whereas it decreasedtissue compliance by 37%. Compared with the unanesthetized condition, the methacholine challenge (20 µg/kg) resulted in an increase incentral and peripheral airway resistance (69 and 319%, respectively) and a decrease in bronchial airway wall and tissue compliance (37 and79%, respectively). This technique is capable of measuring Ztr inanesthetized and awake guinea pigs. Analysis of these data with thiseight-element model provides reasonable estimates of airway and tissueparameters.

     

Sprint training, in vitro and in vivo muscle function, and myosin heavy chain expression

Harridge, S. D. R., R. Bottinelli, M. Canepari, M. Pellegrino, C. Reggiani, M. Esbjörnsson, P. D. Balsom, and B. Saltin. Sprint training, in vitro and in vivo muscle function, and myosin heavy chain expression. J. Appl.Physiol. 84(2): 442-449, 1998.Sprint trainingrepresents the condition in which increases in muscle shortening speed,as well as in strength, might play a significant role in improvingpower generation. This study therefore aimed to determine the effectsof sprint training on 1) thecoupling between myosin heavy chain (MHC) isoform expression andfunction in single fibers, 2) thedistribution of MHC isoforms across a whole muscle, and3) in vivo muscle function. Sevenyoung male subjects completed 6 wk of training (3-s sprints) on a cycleergometer. Training was without effect on maximum shortening velocityin single fibers or in the relative distribution of MHC isoforms ineither the soleus or the vastus lateralis muscles. Electrically evokedand voluntary isometric torque generation increased(P < 0.05) after training in boththe plantar flexors (+8% at 50 Hz and +16% maximal voluntarycontraction) and knee extensors (+8% at 50 Hz and +7% maximalvoluntary contraction). With the shortening potential of the musclesapparently unchanged, the increased strength of the major lower limbmuscles is likely to have contributed to the 7% increase(P < 0.05) in peak pedal frequency during cycling.

     

Contractions of specific abdominal muscles in postural tasks are affected by respiratory maneuvers

Hodges, Paul W., Simon C. Gandevia, and Carolyn A. Richardson. Contractions of specific abdominalmuscles in postural tasks are affected by respiratory maneuvers.J. Appl. Physiol. 83(3): 753-760, 1997.The influence of respiratory activity of the abdominal muscleson their reaction time in a postural task was evaluated. Theelectromyographic (EMG) onsets of the abdominal muscles and deltoidwere evaluated in response to shoulder flexion initiated by a visualstimulus occurring at random throughout the respiratory cycle.Increased activity of the abdominal muscles was produced by inspiratoryloading, forced expiration below functional residual capacity, and astatic glottis-closed expulsive maneuver. During quiet breathing, thelatency between activation of the abdominal muscles and deltoid was notinfluenced by the respiratory cycle. When respiratory activity of theabdominal muscles increased, the EMG onset of transversus abdominis andinternal oblique, relative to deltoid, was significantly earlier formovements beginning in expiration, compared with inspiration [by97-107 ms (P < 0.01) and64-90 ms (P < 0.01),respectively]. However, the onset of transversus abdominis EMGwas delayed by 31-54 ms (P < 0.01) when movement was performed during a static expulsive effort,compared with quiet respiration. Thus changes occur in earlyanticipatory contraction of transversus abdominis during respiratorytasks but they cannot be explained simply by existing activation of themotoneuron pool.

     

Potentiation of in vitro concentric work in mouse fast muscle

Grange, R. W., R. Vandenboom, J. Xeni, and M. E. Houston.Potentiation of in vitro concentric work in mouse fast muscle. J. Appl. Physiol. 84(1): 236-243, 1998.Phosphorylation of myosin regulatory light chain (R-LC) isassociated with potentiated work and power during twitch afterloadedcontractions in mouse extensor digitorum longus muscle [R. W. Grange, C. R. Cory, R. Vandenboom, and M. E. Houston.Am. J. Physiol. 269 (Cell Physiol. 38): C713-C724, 1995]. We now describe the association between R-LCphosphorylation and potentiated concentric work when the extensordigitorum longus muscle is rhythmically shortened and lengthened tosimulate contractions in vivo. Work output (at 25°C) wascharacterized at sine frequencies of 3, 5, 7, 10, and 15 Hz atexcursions of 0.6, 1.2, and 1.6 mm (~5, 9, and 13% optimal musclelength) at a low level of R-LC phosphorylation. Muscles stimulatedduring the sine function with a single twitch at specific times beforeor after the longest muscle length yielded maximal concentric work nearthe longest muscle length at a sine frequency of 7 Hz (e.g., excursion~9% optimal muscle length = 1.6 J/kg). Power increased linearlybetween sine frequencies of 3 and 15 Hz at all excursions (maximum~29 W). After a 5-Hz 20-s conditioning stimulus and coincident with a3.7-fold increase in R-LC phosphate content (e.g., from 0.19 to 0.70 mol phosphate/mol R-LC), work at the three excursions and a sinefrequency of 7 Hz was potentiated a mean of 25, 44, and 50%(P < 0.05), respectively. Thepotentiated work during rhythmic contractions is consistent withenhanced interaction between actin and myosin in the force-generatingstates. On the basis of observations in skinned skeletal muscle fibers(H. L. Sweeney and J. T. Stull. Proc. Natl. Acad. Sci.USA 87: 414-418, 1990), this enhancement couldresult from increased phosphate incorporation by the myosin R-LC. Underthe assumption that the predominant effect of the conditioning stimuluswas to increase R-LC phosphate content, our data suggest that a similarmechanism may be evident in intact muscle.

     

Effect of tidal volume and frequency on airway responsiveness in mechanically ventilated rabbits

Shen, X., S. J. Gunst, and R. S. Tepper. Effect oftidal volume and frequency on airway responsiveness in mechanically ventilated rabbits. J. Appl. Physiol.83(4): 1202-1208, 1997.We evaluated the effects of the rate andvolume of tidal ventilation on airway resistance (Raw) duringintravenous methacholine (MCh) challenge in mechanically ventilatedrabbits. Five rabbits were challenged at tidal volumes of 5, 10, and 20 ml/kg at a frequency of 15 breaths/min and also under static conditions(0 ml/kg tidal volume). Four rabbits were subjected to MCh challenge atfrequencies of 6 and 30 breaths/min with a tidal volume of 10 ml/kg andalso under static conditions. In both groups, the increase in Raw with MCh challenge was significantly greater under static conditions thanduring tidal ventilation at any frequency or volume. Increases in thevolume or frequency of tidal ventilation resulted in significant decreases in Raw in response to MCh. We conclude that tidal breathing suppresses airway responsiveness in rabbits in vivo. The suppression ofnarrowing in response to MCh increases as the magnitude of the volumeor the frequency of the tidal oscillations is increased. Our findingssuggest that the effect of lung volume changes on airway responsivenessin vivo is primarily related to the stretch of airway smooth muscle.

     

Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency

Wolfson, Marla R., Nancy E. Kechner, Robert F. Roache,Jean-Pierre DeChadarevian, Helena E. Friss, S. David Rubenstein, andThomas H. Shaffer. Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency. J. Appl. Physiol. 84(2): 624-640, 1998.To test the hypotheses that perfluorochemical (PFC) liquidrescue after natural surfactant (SF) treatment would improve pulmonaryfunction and histology and that this profile would be influenced by PFCdose or ventilator strategy, anesthetized preterm lambs(n = 31) with respiratory distresswere studied using nonpreoxygenated perflubron. All animals received SFat 1 h and were randomized at 2 h as follows and studied to 4 h postnatal age: 1) conventionalmechanical gas ventilation (n = 8),2) 30 ml/kg perflubron with gasventilation [partial liquid ventilation (PLV)] at 60 breaths/min (n = 8),3) 10 ml/kg perflubron with PLV at60 breaths/min (n = 7), and4) 10 ml/kg perflubron with PLV at30 breaths/min (n = 8). All animalstolerated instillation without additional cardiopulmonary instability.All perflubron-rescued groups demonstrated sustained improvement in gasexchange, respiratory compliance, and reduction in pressure requirements relative to animals receiving SF alone. Improvement wasdirectly related to perflubron dose and breathing frequency; peakinspiratory pressure required to achieve physiological gas exchange waslower in the higher-dose and -frequency groups, and mean airwaypressure was lower in the lower-frequency group. Lung expansion wasgreater and evidence of barotrauma was less in the higher-dose and-frequency group; regional differences in expansion were not differentas a function of dose but were greater in the lower-frequency group.Regional differences in lung perflubron content were reduced in thehigher-dose and -frequency groups and greatest in the lower-dose and-frequency group. The results suggest that, whereas PLV of theSF-treated lung improves gas exchange and lung mechanics, theprotective benefits of perflubron in the lung may depend on dose andventilator strategy to optimize PFC distribution and minimize exposureof the alveolar-capillary membrane to a gas-liquid interface.

     

Vasomotor instability preceding tilt-induced syncope: does respiration play a role?

Lipsitz, Lewis A., Raymond Morin, Margaret Gagnon, DanKiely, and Aharon Medina. Vasomotor instability precedingtilt-induced syncope: does respiration play a role? J. Appl. Physiol. 83(2): 383-390, 1997.This studyaimed to determine whether alterations in cardiovascular dynamicsbefore syncope are related to changes in spontaneous respiration.Fifty-two healthy subjects underwent continuous heart rate (HR),arterial blood pressure (BP), and respiratory measurements during10-min periods of spontaneous and paced breathing (0.25 Hz) in thesupine and 60° head-up tilt positions. Data were evaluated by powerspectrum and transfer function analyses. During tilt, 27 subjectsdeveloped syncope or presyncope and 25 remained asymptomatic. Subjectswith tilt-induced syncope had significantly greater increases inlow-frequency (0.04-0.15 Hz) systolic BP, diastolic BP, and HRpower during tilt than the asymptomatic subjects(P  0.01). This difference waspresent during spontaneous but not paced breathing. However, averagetidal volume, respiratory rate, minute ventilation, proportion ofbreaths below 0.15 Hz, and low-frequency respiratory power during tilt did not differ between syncopal and nonsyncopal subjects. Transfer magnitudes between low-frequency respiration and BP, and between BP andinterbeat interval, were also similar between groups. Thus vasomotorinstability before syncope is not related to alterations in respirationor the cardiovagal baroreflex but may reflect oscillating centralsympathetic outflow to the vasculature.

     

Rate and composition of sweat fluid losses are unaltered by hypohydration during prolonged exercise in horses

Kingston, Janene K., Raymond J. Geor, and Laura JillMcCutcheon. Rate and composition of sweat fluid losses areunaltered by hypohydration during prolonged exercise in horses.J. Appl. Physiol. 83(4):1133-1143, 1997. Rate and ionic composition of sweat fluid losses and partitioning of evaporative heat loss into respiratory and cutaneous components were determined in six horses during three 15-km phases of exercise at ~40% of maximalO₂ uptake. Pattern of change insweat rate (SR) and composition was similar during each phase. SRincreased rapidly for the first 20 min of exercise but remained at~24-28ml · m² · min¹during the remainder of each phase. Similarly, the concentrations of Naand Cl in sweat increased until 30 min of exercise but were unchangedthereafter. Sweat osmolality and concentrations of Na and Cl werepositively correlated with SR. Sweat K concentration decreased duringexercise but was not correlated with SR. Fluid losses were 33.8 ± 1.5 liters, resulting in decreases of ~21% in plasma volume and~11% in total body water. The ~6% hypohydration was notassociated with an alteration in SR, sweat composition, or heatstorage. Respiratory and cutaneous evaporative heat loss represented~23 and 70%, respectively, of the total heat dissipated, and thepartitioning of heat loss was similar in each exercise phase. Weconclude that SR and the relative proportions of respiratory andcutaneous evaporative heat loss are unchanged in horses during prolonged low-intensity exercise despite moderate hypohydration.

     

Intensity and frequency dependence of laryngeal afferent inputs to respiratory hypoglossal motoneurons

Mifflin, Steven W. Intensity and frequency dependenceof laryngeal afferent inputs to respiratory hypoglossal motoneurons. J. Appl. Physiol. 83(6):1890-1899, 1997.Inspiratory hypoglossal motoneurons (IHMs)mediate contraction of the genioglossus muscle and contribute to theregulation of upper airway patency. Intracellular recordings wereobtained from antidromically identified IHMs in anesthetized,vagotomized cats, and IHM responses to electrical activation ofsuperior laryngeal nerve (SLN) afferent fibers at various frequenciesand intensities were examined. SLN stimulus frequencies <2 Hz evokedan excitatory-inhibitory postsynaptic potential (EPSP-IPSP) sequence oronly an IPSP in most IHMs that did not change in amplitude as thestimulus was maintained. During sustained stimulus frequencies of5-10 Hz, there was a reduction in the amplitude of SLN-evokedIPSPs with time with variable changes in the EPSP. At stimulusfrequencies >25 Hz, the amplitude of EPSPs and IPSPs was reduced overtime. At a given stimulus frequency, increasing stimulus intensityenhanced the decay of the SLN-evoked postsynaptic potentials (PSPs).Frequency-dependent attenuation of SLN inputs to IHMs also occurred innewborn kittens. These results suggest that activation of SLN afferentsevokes different PSP responses in IHMs depending on the stimulusfrequency. At intermediate frequencies, inhibitory inputs areselectively filtered so that excitatory inputs predominate. At higherfrequencies there was no discernible SLN-evoked PSP temporally lockedto the SLN stimuli. Alterations in SLN-evoked PSPs could play a role inthe coordination of genioglossal contraction during respiration,swallowing, and other complex motor acts where laryngeal afferents areactivated.

     

Gas compression in lungs decreases peak expiratory flow depending on resistance of peak flowmeter

Pedersen, O. F., T. F. Pedersen, and M. R. Miller. Gascompression in lungs decreases peak expiratory flow depending onresistance of peak flowmeter. J. Appl.Physiol. 83(5): 1517-1521, 1997.It has recentlybeen shown (O. F. Pedersen T. R. Rasmussen, Ø. Omland, T. Sigsgaard, P. H. Quanjer, and M. R. Miller. Eur. Respir. J. 9: 828-833, 1996) that the addedresistance of a mini-Wright peak flowmeter decreases peak expiratoryflow (PEF) by ~8% compared with PEF measured by a pneumotachograph.To explore the reason for this, 10 healthy men (mean age 43 yr, range33-58 yr) were examined in a body plethysmograph with facilitiesto measure mouth flow vs. expired volume as well as the change inthoracic gas volume (Vb) and alveolar pressure(PA). The subjects performed forced vital capacity maneuvers through orifices of different sizes andalso a mini-Wright peak flowmeter. PEF with the meter and other addedresistances were achieved when flow reached the perimeter of theflow-Vb curves. The mini-Wright PEF meter decreased PEF from 11.4 ± 1.5 to 10.3 ± 1.4 (SD) l/s(P < 0.001),PA increased from 6.7 ± 1.9 to 9.3 ± 2.7 kPa (P < 0.001), anincrease equal to the pressure drop across the meter, and caused Vb atPEF to decrease by 0.24 ± 0.09 liter(P < 0.001). We conclude that PEF obtained with an added resistance like a mini-Wright PEF meter is awave-speed-determined maximal flow, but the added resistance causes gascompression because of increasedPA at PEF. Therefore, Vb at PEFand, accordingly, PEF decrease.

     

Analysis of perfluorochemical elimination from the respiratory system

Shaffer, Thomas H., Raymond Foust IIII, Marla R. Wolfson,and Thomas F. Miller, Jr. Analysis of perfluorochemicalelimination from the respiratory system. J. Appl.Physiol. 83(3): 1033-1040, 1997.We describe asimple apparatus for analysis of perfluorochemicals (PFC) in expiredgas and thus a means for determining PFC vapor and liquid eliminationfrom the respiratory system. The apparatus and data analysis are basedon thermal conduction and mass transfer principles of gases. In vitrostudies were conducted with the PFC vapor analyzer to determinecalibration curves for output voltage as a function of individualrespiratory gases, respiratory gases saturated with PFC vapor, andvolume percent standards for percent PFC saturation (%PFC-Sat) in air.Voltage-concentration data for %PFC-Sat of the vapor from the in vitrotests were accurate to within 2.0% from 0 to 100% PFC-Sat, linear(r = 0.99, P < 0.001), and highly reproducible.Calculated volume loss of PFC liquid over time correlated well withactual loss by weight (r = 0.99, P < 0.001). In vivo studies withneonatal lambs demonstrated that PFC volume loss and evaporation ratesdecreased nonlinearly as a function of time. These relationships weremodulated by changes in PFC physical properties, minute ventilation,and postural repositioning. The results of this study demonstrate thesensitivity and accuracy of an on-line method for PFC analysis ofexpired gas and describe how it may be useful in liquid-assistedventilation procedures for determining PFC volume loss, evaporationrate, and optimum dosing and ventilation strategy.

     

Greater airway narrowing in immature than in mature rabbits during methacholine challenge

Shen, X., V. Bhargava, G. R. Wodicka, C. M. Doerschuk, S. J. Gunst, and R. S. Tepper. Greater airway narrowing in immature thanin mature rabbits during methacholine challenge. J. Appl. Physiol. 81(6): 2637-2643, 1996.It hasbeen demonstrated that methacholine (MCh) challenge produces a greaterincrease in lung resistance in immature than in mature rabbits (R. S. Tepper, X. Shen, E. Bakan, and S. J. Gunst.J. Appl. Physiol. 79: 1190-1198, 1995). To determine whether this maturational difference in the response to MCh was primarily related to changes in airway resistance (Raw) or changes in tissue resistance, we assessed airway narrowing in1-, 2-, and 6-mo-old rabbits during intravenous MCh challenge (0.01-5.0 mg/kg). Airway narrowing was determined frommeasurements of Raw in vivo and from morphometric measurements on lungsections obtained after rapidly freezing the lung after the MChchallenge. The fold increase in Raw was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. Similarly, the degree of airway narrowing assessed morphometrically was significantly greaterfor 1- and 2-mo-old animals than for 6-mo-old animals. The foldincrease in Raw was highly correlated with the degree of airwaynarrowing assessed morphometrically(r² = 0.82, P < 0.001). We conclude that thematurational difference in the effect of MCh on lung resistance isprimarily caused by greater airway narrowing in the immature rabbits.

     

Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia

LaManna, J. C., M. A. Haxhiu, K. L. Kutina-Nelson, S. Pundik, B. Erokwu, E. R. Yeh, W. D. Lust, and N. S. Cherniack.Decreased energy metabolism in brain stem during centralrespiratory depression in response to hypoxia. J. Appl. Physiol. 81(4): 1772-1777, 1996.Metabolic changes in the brain stem were measured at the time when oxygen deprivation-induced respiratory depression occurred. Eucapnic ventilation with 8% oxygen in vagotomized urethan-anesthetized ratsresulted in cessation of respiratory drive, monitored by recordingdiaphragm electromyographic activity, on average within 11 min (range5-27 min), presumably via central depressant mechanisms. At thattime, the brain stems were frozen in situ for metabolic analyses. Byusing 20-µm lyophilized sections from frozen-fixed brainstem, microregional analyses of ATP, phosphocreatine, lactate, andintracellular pH were made from 1)the ventral portion of the nucleus gigantocellularis and theparapyramidal nucleus; 2) thecompact and ventral portions of the nucleus ambiguus;3) midline neurons;4) nucleus tractus solitarii; and5) the spinal trigeminal nucleus. Atthe time of respiratory depression, lactate was elevated threefold inall regions. Both ATP and phosphocreatine were decreased to 50 and 25%of control, respectively. Intracellular pH was more acidic by0.2-0.4 unit in these regions but was relatively preserved in thechemosensitive regions near the ventral and dorsal medullary surfaces.These results show that hypoxia-induced respiratory depression wasaccompanied by metabolic changes within brain stem regions involved inrespiratory and cardiovascular control. Thus it appears that there wassignificant energy deficiency in the brain stem after hypoxia-inducedrespiratory depression had occurred.

     

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.