A finite-element model of oxygen diffusion in the pulmonary capillaries

Frank, Andreas O., C. J. Charles Chuong, and Robert L. Johnson. A finite-element model of oxygen diffusion in thepulmonary capillaries. J. Appl.Physiol. 82(6): 2036-2044, 1997.We determined the overall pulmonary diffusing capacity(DL) and the diffusing capacities of the alveolar membrane (Dm) and the red blood cell (RBC)segments (De) of the diffusional pathway forO₂ by using a two-dimensionalfinite-element model developed to represent the sheet-flowcharacteristics of pulmonary capillaries. An axisymmetric model wasalso considered to assess the effect of geometric configuration. Results showed the membrane segment contributing the major resistance, with the RBC segment resistance increasing asO₂ saturation(SO₂) rises during the RBC transit:RBC contributed 7% of the total resistance at the capillary inlet (SO₂ = 75%) and 30% toward thecapillary end (SO₂ = 95%) for a 45%hematocrit (Hct). Both Dm and DLincreased as the Hct increased but began approaching a plateau near anHct of 35%, due to competition between RBCs forO₂ influx. Both Dm andDL were found to be relatively insensitive (2~4%) to changes in plasma protein concentration (28~45%). Axisymmetric results showed similar trends for all Hct andprotein concentrations but consistently overestimated the diffusingcapacities (~2.2 times), primarily because of an exaggerated air-tissue barrier surface area. The two-dimensional model correlated reasonably well with experimental data and can better represent theO₂ uptake of the pulmonarycapillary bed.

     

Pulmonary diffusing capacities for oxygen-labeled CO2 and nitric oxide in rabbits

Heller, Hartmut, Gabi Fuchs, and Klaus-DieterSchuster. Pulmonary diffusing capacities foroxygen-labeled CO₂ and nitric oxide in rabbits.J. Appl. Physiol. 84(2): 606-611, 1998.We determined the pulmonary diffusing capacity(DL) for¹⁸O-labeledCO₂(C¹⁸O₂)and nitric oxide (NO) to estimate the membrane component of therespective gas conductances. Six anesthetized paralyzed rabbits wereventilated by a computerized ventilatory servo system. Single-breath maneuvers were automatically performed by inflating the lungs with gasmixtures containing 0.9%C¹⁸O₂or 0.05% NO in nitrogen, with breath-holding periods ranging from 0 to1 s forC¹⁸O₂and from 2 to 8 s for NO. The alveolar partial pressures of C¹⁸O₂and NO were determined by using respiratory mass spectrometry. DL was calculated from gasexchange during inflation, breath hold, and deflation. We obtainedvalues of 14.0 ± 1.1 and 2.2 ± 0.1 (mean value ± SD)ml · mmHg¹ · min¹forDL_C¹⁸O2and DL_NO,respectively. The measured DL_C¹⁸O2/DL_NOratio was one-half that of the theoretically predicted value accordingto Graham's law (6.3 ± 0.5 vs. 12, respectively).Analyses of the several mechanisms influencing the determination ofDL_C¹⁸O2and DL_NOand their ratio are discussed. An underestimation of the membranediffusing component for CO₂ isconsidered the likely reason for the lowDL_C¹⁸O2/DL_NOratio obtained.

     

Restricted postexercise pulmonary diffusion capacity and central blood volume depletion

Hanel, Birgitte, Inge Teunissen, Alan Rabøl,Jørgen Warberg, and Niels H. Secher. Restricted postexercisepulmonary diffusion capacity and central blood volume depletion.J. Appl. Physiol. 83(1): 11-17, 1997.Pulmonary diffusion capacity for carbon monoxide(DL_CO),regional electrical impedance(Z₀), and the distribution oftechnetium-99m-labeled erythrocytes together with concentration ofplasma atrial natriuretic peptide (ANP) were determined before andafter a 6-min "all-out" row in nine oarsmen and in six controlsubjects. Two and one-half hours after exercise in the upright seatedposition,DL_CO wasreduced by 6 (2 to 21; median and range) %, thethoracic-to-thigh electrical impedance ratio(Z_{0 thorax}/Z_{0 thigh})rose by 14 (1 to 29) %, paralleled by a 7 (3 to 11) % decrease and a 3 (5 to 12) % increase in the thoracic and thighblood volume, respectively. These responses were associated with adecrease in the plasma ANP concentration from 15 (13-31) to 12 (9-27) pmol/l (P < 0.05).Similarly, in the supine position,Z_{0 thorax}/Z_{0 thigh}increased by 10 (5 to 28) % whenDL_CO wasreduced 12 (6-26) % (P < 0.05), whereasDL_CO remained stable in the control group. The increase inZ_{0 thorax}/Z_{0 thigh} and the corresponding redistribution of the blood volume in both bodypositions show that approximately one-half of the postexercise reduction ofDL_CO isexplained by a decrease in the pulmonary blood volume. The role of areduced postexercise central blood volume is underscored by the lowerplasma ANP, which aids in upregulating the blood volume after exercisein athletes.

     

Hypoxia, temperature, and pH/CO2 effects on respiratory discharge from a turtle brain stem preparation

Johnson, Stephen M., Rebecca A. Johnson, and Gordon S. Mitchell. Hypoxia, temperature, andpH/CO₂ effects on respiratory discharge from a turtle brain stem preparation. J. Appl. Physiol. 84(2): 649-660, 1998.An in vitrobrain stem preparation from adult turtles (Chrysemyspicta) was used to examine the effects of anoxia andincreased temperature and pH/CO₂on respiration-related motor output. At pH ~7.45, hypoglossal (XII)nerve roots produced patterns of rhythmic bursts (peaks) of discharge(0.74 ± 0.07 peaks/min, 10.0 ± 0.6 s duration) that werequantitatively similar to literature reports of respiratory activity inconscious, vagotomized turtles. Respiratory discharge was stable for 6 h at 22°C; at 32°C, peak amplitude and frequency progressivelyand reversibly decreased with time. Two hours of hypoxia had no effecton respiratory discharge. Acutely increasing bath temperature from 22 to 32°C decreased episode and peak duration and increased peakfrequency. Changes in pH/CO₂increased peak frequency from zero at pH 8.00-8.10 to maxima of0.81 ± 0.01 and 1.44 ± 0.02 peaks/min at 22°C (pH 7.32) and32°C (pH 7.46), respectively;pH/CO₂ sensitivity was similar atboth temperatures. We conclude that1) insensitivity to hypoxiaindicates that rhythmic discharge does not reflect gasping behavior,2) increased temperature altersrespiratory discharge, and 3)central pH/CO₂ sensitivity isunaffected by temperature in this preparation (i.e.,Q₁₀ ~1.0).

     

Evaluation of estimates of alveolar gas exchange by using a tidally ventilated nonhomogenous lung model

Busso, Thierry, and Peter A. Robbins. Evaluation ofestimates of alveolar gas exchange by using a tidally ventilated nonhomogenous lung model. J. Appl.Physiol. 82(6): 1963-1971, 1997.The purposeof this study was to evaluate algorithms for estimatingO₂ andCO₂ transfer at thepulmonary capillaries by use of a nine-compartment tidallyventilated lung model that incorporated inhomogeneities inventilation-to-volume and ventilation-to-perfusion ratios.Breath-to-breath O₂ andCO₂ exchange at the capillary level and at the mouth were simulated by using realistic cyclical breathing patterns to drive the model, derived from 40-min recordings in six resting subjects. The SD of the breath-by-breath gas exchange atthe mouth around the value at the pulmonary capillaries was 59.7 ± 25.5% for O₂ and 22.3 ± 10.4% for CO₂. Algorithmsincluding corrections for changes in alveolar volume and for changes in alveolar gas composition improved the estimates of pulmonary exchange, reducing the SD to 20.8 ± 10.4% forO₂ and 15.2 ± 5.8% forCO₂. The remaining imprecision ofthe estimates arose almost entirely from using end-tidal measurementsto estimate the breath-to-breath changes in end-expiratory alveolar gasconcentration. The results led us to suggest an alternative method thatdoes not use changes in end-tidal partial pressures as explicitestimates of the changes in alveolar gas concentration. The proposedmethod yielded significant improvements in estimation for the modeldata of this study.

     

Ultrasound evaluation of piglet diaphragm function before and after fatigue

Kocis, Keith C., Peter J. Radell, Wayne I. Sternberger, JaneE. Benson, Richard J. Traystman, and David G. Nichols. Ultrasound evaluation of piglet diaphragm function before and after fatigue. J. Appl. Physiol. 83(5):1654-1659, 1997.Clinically, a noninvasive measure of diaphragmfunction is needed. The purpose of this study is to determine whetherultrasonography can be used to 1)quantify diaphragm function and 2)identify fatigue in a piglet model. Five piglets were anesthetized withpentobarbital sodium and halothane and studied during the followingconditions: 1) baseline (spontaneous breathing); 2) baseline + CO₂ [inhaledCO₂ to increase arterial PCO₂ to 50-60 Torr (6.6-8kPa)]; 3) fatigue + CO₂ (fatigue induced with 30 minof phrenic nerve pacing); and 4)recovery + CO₂ (recovery after 1 hof mechanical ventilation). Ultrasound measurements of the posteriordiaphragm were made (inspiratory mean velocity) in the transverseplane. Images were obtained from the midline, just inferior to thexiphoid process, and perpendicular to the abdomen. M-mode measures weremade of the right posterior hemidiaphragm in the plane just lateral tothe inferior vena cava. Abdominal and esophageal pressures weremeasured and transdiaphragmatic pressure (Pdi) was calculated duringspontaneous (Sp) and paced (Pace) breaths. Arterial blood gases werealso measured. Pdi(Sp) and Pdi(Pace)during baseline + CO₂ were 8 ± 0.7 and 49 ± 11 cmH₂O, respectively, anddecreased to 6 ± 1.0 and 27 ± 7 cmH₂O,respectively, during fatigue + CO₂. Mean inspiratory velocityalso decreased from 13 ± 2 to 8 ± 1 cm/s during theseconditions. All variables returned to baseline during recovery + CO₂. Ultrasonography can beused to quantify diaphragm function and identify piglet diaphragm fatigue.

     

Pulmonary diffusing capacity and pulmonary capillary blood volume during parabolic flights

Vaïda, Pierre, Christian Kays, Daniel Rivière,Pierre Téchoueyres, and Jean-Luc Lachaud.Pulmonary diffusing capacity and pulmonary capillary blood volumeduring parabolic flights. J. Appl.Physiol. 82(4): 1091-1097, 1997.Data from theSpacelab Life Sciences-1 (SLS-1) mission have shown sustained butmoderate increase in pulmonary diffusing capacity(DL). Because of the occupational constraints of the mission, data were only obtained after24 h of exposure to microgravity. Parabolic flights are often used tostudy some effects of microgravity, and we measured changes inDL occurring at the very onsetof weightlessness. Measurements ofDL, membrane diffusing capacity,and pulmonary capillary blood volume were made in 10 male subjectsduring the 20-s 0-G phases of parabolic flights performed by the"zero-G" Caravelle aircraft. Using the standardized single-breathtechnique, we measuredDL for CO andnitric oxide simultaneously. We found significant increases inDL for CO (62%),in membrane diffusing capacity for CO (47%), inDL for nitric oxide (47%), andin pulmonary capillary blood volume (71%). We conclude that majorchanges in the alveolar membrane gas transfers and in the pulmonarycapillary bed occur at the very onset of microgravity. Because thesechanges are much greater than those reported during sustainedmicrogravity, the effects of rapid transition from hypergravity tomicrogravity during parabolic flights remain questionable.

     

Effects of inhaled CO2 and added dead space on idiopathic central sleep apnea

Xie, Ailiang, Fiona Rankin, Ruth Rutherford, and T. DouglasBradley. Effects of inhaledCO₂ and added dead space on idiopathic central sleep apnea. J. Appl.Physiol. 82(3): 918-926, 1997.We hypothesizedthat reductions in arterial PCO₂ (Pa_CO2) below the apnea threshold play akey role in the pathogenesis of idiopathic central sleep apnea syndrome(ICSAS). If so, we reasoned that raisingPa_CO2 would abolish apneas in thesepatients. Accordingly, patients with ICSAS were studied overnight onfour occasions during which the fraction of end-tidalCO₂ and transcutaneous PCO₂ were measured: during room airbreathing (N1), alternating room airand CO₂ breathing(N2),CO₂ breathing all night(N3), and addition of dead space viaa face mask all night (N4).Central apneas were invariably preceded by reductions infraction of end-tidal CO₂. Bothadministration of a CO₂-enrichedgas mixture and addition of dead space induced 1- to 3-Torr increasesin transcutaneous PCO₂, whichvirtually eliminated apneas and hypopneas; they decreased from43.7 ± 7.3 apneas and hypopneas/h onN1 to 5.8 ± 0.9 apneas andhypopneas/h during N3(P < 0.005), from 43.8 ± 6.9 apneas and hypopneas/h during room air breathing to 5.9 ± 2.5 apneas and hypopneas/h of sleep duringCO₂ inhalation during N2 (P < 0.01), and to 11.6% of the room air level while the patients werebreathing through added dead space duringN4 (P < 0.005). Because raisingPa_CO2 through two different meansvirtually eliminated central sleep apneas, we conclude that centralapneas during sleep in ICSA are due to reductions inPa_CO2 below the apnea threshold.

     

Letters to the Editor

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

Mitchell, Claire H., Jin Jun Zhang, Liwei Wang, andTim J. C. Jacob. Volume-sensitive chloride current in pigmented ciliary epithelial cells: role of phospholipases. Am. J. Physiol. 272 (Cell Physiol. 41): C212-C222, 1997.Thewhole cell recording technique was used to examine an outwardlyrectifying chloride current activated by hypotonic shock in bovinepigmented ciliary epithelial (PCE) cells. Removal of internal andexternal Ca²⁺ did not affect the activation of thesecurrents, but they were abolished by the phospholipase C inhibitorneomycin. The current was blocked by5-nitro-2-(3-phenylpropylamino)benzoic acid,4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, and4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in avoltage-dependent manner, but tamoxifen, dideoxyforskolin, andquinidine did not affect it. This blocking profile differs from that ofthe volume-sensitive chloride channel in neighboring nonpigmentedciliary epithelial cells (Wu, J., J. J. Zhang, H. Koppel, and T. J. C. Jacob. J. Physiol. Lond. 491: 743-755, 1996), and thisdifference implies that the volume responses of the two cell types aremediated by different chloride channels (Jacob, T. J. C., and J. J. Zhang. J. Physiol. Lond. In press). Intracellular administration of guanosine 5'-O-(3-thiotriphosphate) (GTPS) to PCE cells induced a transient, time-independent, outwardly rectifying chloride current that closely resembled the current activated by hypotonic shock. DIDS produced a voltage-dependent blockof the GTPS-activated current similar to the block of the hypotonically activated current. Intracellular neomycin completely prevented activation of this current as did incubation of the cells incalphostin C, an inhibitor of protein kinase C (PKC). Removal ofCa²⁺ did not affect activation of the current by GTPSbut extended the duration of the response. Inhibition of phospholipaseA₂ (PLA₂) with p-bromophenacyl bromideprevented the activation of the hypotonically induced current and alsoinhibited the current once activated by hypotonic solution. Thefindings imply that the hypotonic response in PCE cells is mediated byboth phospholipase C (PLC) and PLA₂. Both phospholipasesgenerate arachidonic acid, and, in addition, the PLC pathway regulatesthe PLA₂ pathway via a PKC-dependent phosphorylation ofPLA₂.

     

Effects of hypoxic pulmonary vasoconstriction on pulmonary gas exchange

Brimioulle, Serge, Philippe Lejeune, and Robert Naeije.Effects of hypoxic pulmonary vasoconstriction on pulmonary gasexchange. J. Appl. Physiol. 81(4):1535-1543, 1996.Several reports have suggested that hypoxicpulmonary vasoconstriction (HPV) might result in deterioration ofpulmonary gas exchange in severe hypoxia. We therefore investigated theeffects of HPV on gas exchange in normal and diseased lungs. Weincorporated a biphasic HPV stimulus-response curve observed in intactdogs (S. Brimioulle, P. Lejeune, J. L. Vachièry, M. Delcroix, R. Hallemans, and R. Naeije, J. Appl.Physiol. 77: 476-480, 1994) into a 50-compartment lung model (J. B. West, Respir.Physiol. 7: 88-110, 1969) to control the amount ofblood flow directed to each lung compartment according to the localhypoxic stimulus. The resulting model accurately reproduced the bloodgas modifications caused by HPV changes in dogs with acute lung injury.In single lung units, HPV had a moderate protective effect on alveolaroxygenation, which was maximal at near-normal alveolarPO₂ (75-80 Torr), mixed venousPO₂ (35 Torr), andPO₂ at which hemoglobin is 50%saturated (24 Torr). In simulated diseased lungs associated with40-60 Torr arterial PO₂,however, HPV increased arterial PO₂ by 15-20 Torr. We conclude that HPV can improve arterialoxygenation substantially in respiratory failure.

     

Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs

Parker, James C., and Claire L. Ivey.Isoproterenol attenuates high vascular pressure-inducedpermeability increases in isolated rat lungs. J. Appl.Physiol. 83(6): 1962-1967, 1997.To separate thecontributions of cellular and basement membrane components of thealveolar capillary barrier to the increased microvascular permeabilityinduced by high pulmonary venous pressures (Ppv), we subjected isolatedrat lungs to increases in Ppv, which increased capillary filtrationcoefficient(K_fc) withoutsignificant hemorrhage (31 cmH₂O)and with obvious extravasation of red blood cells (43 cmH₂O). Isoproterenol (20 µM)was infused in one group (Iso) to identify a reversible cellularcomponent of injury, and residual blood volumes were measured to assessextravasation of red blood cells through ruptured basement membranes.In untreated lungs (High Ppv group),K_fc increased 6.2 ± 1.3 and 38.3 ± 15.2 times baseline during the 31 and 43 cmH₂O Ppv states. In Iso lungs, K_fc was 36.2%(P < 0.05) and 64.3% of that in theHigh Ppv group at these Ppv states. Residual blood volumes calculatedfrom tissue hemoglobin contents were significantly increased by53-66% in the high Ppv groups, compared with low vascularpressure controls, but there was no significant difference between HighPpv and Iso groups. Thus isoproterenol significantly attenuatedvascular pressure-induced K_fc increases atmoderate Ppv, possibly because of an endothelial effect, but it did notaffect red cell extravasation at higher vascular pressures.

     

When does the lung die? Kfc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung

Jones, David R., Randy M. Becker, Steve C. Hoffmann, John J. Lemasters, and Thomas M. Egan. When does the lungdie? K_fc, cellviability, and adenine nucleotide changes in the circulation-arrested rat lung. J. Appl. Physiol. 83(1):247-252, 1997.Lungs harvested from cadavericcirculation-arrested donors may increase the donor pool for lungtransplantation. To determine the degree and time course ofischemia-reperfusion injury, we evaluated the effect ofO₂ ventilation on capillarypermeability [capillary filtration coefficient(K_fc)],cell viability, and total adenine nucleotide (TAN) levels in in situcirculation-arrested rat lungs.K_fc increased with increasing postmortem ischemic time(r = 0.88). Lungs ventilated withO₂ 1 h postmortem had similarK_fc andwet-to-dry ratios as controls. Nonventilated lungs had threefold(P < 0.05) and sevenfold (P < 0.0001) increases inK_fc at 30 and 60 min postmortem compared with controls. Cell viability decreased inall groups except for 30-min postmortemO₂-ventilated lungs. TAN levelsdecreased with increasing ischemic time, particularly in nonventilatedlungs. Loss of adenine nucleotides correlated with increasingK_fc values (r = 0.76). This study indicates thatlungs retrieved 1 h postmortem may have normalK_fc withpreharvest O₂ ventilation. Therelationship betweenK_fc and TANsuggests that vascular permeability may be related to lung TAN levels.

     

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.

     

Effect of PCMBS on CO2 permeability of Xenopus oocytes expressing aquaporin 1or its C189S mutant

A recent study onXenopus oocytes [N. L. Nakhoul,M. F. Romero, B. A. Davis, and W. F. Boron. Am. J. Physiol. 274 (CellPhysiol. 43): C543-548, 1998] injected withcarbonic anhydrase showed that expressing aquaporin 1 (AQP1) increasesby ~40% the rate at which exposing the cell toCO₂ causes intracellular pH tofall. This observation is consistent with several interpretations.Overexpressing AQP1 might increase apparentCO₂ permeability by1) allowingCO₂ to pass through AQP1,2) stimulating injected carbonicanhydrase, 3) enhancing theCO₂ solubility of the membrane'slipid, or 4) increasing theexpression of a native "gas channel." The purpose of the presentstudy was to distinguish among these possibilities. We found thatexpressing the H₂O channel AQP1 inXenopus oocytes increases theCO₂ permeability of oocytes in anexpression-dependent fashion, whereas expressing theK⁺ channel ROMK1 has no effect.The mercury derivativep-chloromercuriphenylsulfonic acid(PCMBS), which inhibits the H₂Omovement through AQP1, also blocks the AQP1-dependent increase inCO₂ permeability. Themercury-insensitive C189S mutant of AQP1 increases theCO₂ permeability of the oocyte tothe same extent as does the wild-type channel. However, the C189S-dependent increase in CO₂permeability is unaffected by treatment with PCMBS. These data rule outoptions 2-4 listed above. Thusour results suggest that CO₂passes through the pore of AQP1 and are the first data to demonstratethat a gas can enter a cell by a means other than diffusing through themembrane lipid.

     

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity

Verbanck, Sylvia, Hans Larsson, Dag Linnarsson, G. KimPrisk, John B. West, and Manuel Paiva. Pulmonary tissue volume, cardiac output and diffusing capacity in sustained microgravity. J. Appl. Physiol. 83(3): 810-816, 1997.In microgravity (µG) humans have marked changes in bodyfluids, with a combination of an overall fluid loss and aredistribution of fluids in the cranial direction. We investigatedwhether interstitial pulmonary edema develops as a result of a headwardfluid shift or whether pulmonary tissue fluid volume is reduced as aresult of the overall loss of body fluid. We measured pulmonary tissuevolume (Vti), capillary blood flow, and diffusing capacity in foursubjects before, during, and after 10 days of exposure to µG duringspaceflight. Measurements were made by rebreathing a gas mixturecontaining small amounts of acetylene, carbon monoxide, and argon.Measurements made early in flight in two subjects showed no change inVti despite large increases in stroke volume (40%) and diffusingcapacity (13%) consistent with increased pulmonary capillary bloodvolume. Late in-flight measurements in four subjects showed a 25%reduction in Vti compared with preflight controls(P < 0.001). There was aconcomittant reduction in stroke volume, to the extent that it was nolonger significantly different from preflight control. Diffusingcapacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despiteincreased pulmonary perfusion and pulmonary capillary blood volume,interstitial pulmonary edema does not result from exposure to µG.

     

Task failure with lack of diaphragm fatigue during inspiratory resistive loading in human subjects

McKenzie, D. K., G. M. Allen, J. E. Butler, and S. C. Gandevia. Task failure with lack of diaphragm fatigue during inspiratory resistive loading in human subjects. J. Appl. Physiol. 82(6): 2011-2019, 1997.Taskfailure during inspiratory resistive loading is thought to beaccompanied by substantial peripheral fatigue of the inspiratorymuscles. Six healthy subjects performed eight resistive breathingtrials with loads of 35, 50, 75 and 90% of maximal inspiratorypressure (MIP) with and without supplemental oxygen. MIP measuredbefore, after, and at every minute during the trial increased slightlyduring the trials, even when corrected for lung volume (e.g., for 24 trials breathing air, 12.5% increase, P < 0.05). In some trials, taskfailure occurred before 20 min (end point of trial), and in thesetrials there was an increase in end-tidalPCO₂(P < 0.01), despite the absence of peripheral muscle fatigue. In four subjects (6 trials with task failure), there was no decline in twitch amplitude with bilateral phrenic stimulation or in voluntary activation of the diaphragm, eventhough end-tidal PCO₂ rose by 1.6 ± 0.9%. These results suggest that hypoventilation,CO₂ retention, and ultimate taskfailure during resistive breathing are not simply dependent on impairedforce-generating capacity of the diaphragm or impaired voluntaryactivation of the diaphragm.

     

Focal central chemoreceptor sensitivity in the RTN studied with a CO2 diffusion pipette in vivo

Li, Aihua, and Eugene E. Nattie. Focal centralchemoreceptor sensitivity in the RTN studied with aCO₂ diffusion pipette in vivo.J. Appl. Physiol. 83(2): 420-428, 1997.We describe and use a CO₂diffusion pipette to produce a quickly reversible focal acidosis in theretrotrapezoid nucleus region of the rat brain stem. No tissueinjection is made. Instead, artificial cerebrospinal fluid (aCSF)equilibrated with CO₂ circulateswithin the micropipette, providing a source for continuedCO₂ diffusion into the tissue fromthe pipette tip. Tissue pH electrodes show the acidosis is limited to500 µm from the tip. In controls (aCSF equilibrated with air), 1-minpipette perfusions increased tissue pH slightly and decreased phrenicnerve amplitude. In moderate- andhigh-CO₂ groups (aCSF equilibratedwith 50 or 100% CO₂), 1-minperfusions significantly decreased tissue pH and increased phrenicnerve amplitude in a dose-dependent manner. The responses developed andreversed within minutes. Compared with our prior use of medullary acetazolamide injections to produce a focal acidosis, in this approachthe acidosis 1) arises and reversesquickly and 2) its intensity can bevaried. This allows study of sensitivity and mechanism. We concludefrom this initial experiment that retrotrapezoid nucleus regionchemoreceptors operate within the normal physiological range ofCO₂-induced tissue pH changes.

     

Rate of uptake of CO by hemoglobin in pig erythrocytes as a function of PO2

Te Nijenhuis, Francis C. A. M., Lydia Lin, Gerko H. Moens,Adrian Versprille, and Robert E. Forster. Rate of uptake of CO byhemoglobin in pig erythrocytes as a function ofPO₂. J. Appl.Physiol. 81(4): 1544-1549, 1996.This study wasinitiated to obtain data on the rate of carbon monoxide (CO) uptake(_CO) by hemoglobin in pigerythrocytes to derive, in a later study, the pulmonary capillary bloodvolume (Qc) in pigs from the Roughton-Forster relationship. Blood fromfive different female pigs was used. The_CO, the milliliters of CO takenup by 1 ml of whole blood per minute per Torr CO tension, wasdetermined on each blood sample with a continuous-flow rapid-mixingapparatus and double-beam spectrophotometry at 37°C and pH 7.4 atfour or five different PO₂ values.Because the individual regression lines of _CO vs.PO₂ were not significantly different,a common regression equation was calculated:1/_CO = 0.0084 PO₂ + 0.63. The slope of thisregression line is significantly steeper than the reported slopes ofthe regression lines for human and dog erythrocytes measured under thesame conditions. Our results revealed that calculation ofQc in pigs by using _CO valuesfor human or dog erythrocytes would result in an underestimation of 51 and 50%, respectively.

     

CO2 transport in normovolemic anemia: complete compensation and stability of blood CO2 tensions

Deem, Steven A., Michael K. Alberts, Michael J. Bishop,Akhil Bidani, and Erik R. Swenson.CO₂ transport in normovolemic anemia: complete compensation and stability of bloodCO₂ tensions. J. Appl. Physiol. 83(1): 240-246, 1997.Isovolemichemodilution does not appear to impairCO₂ elimination nor causeCO₂ retention despite theimportant role of red blood cells in bloodCO₂ transport. We studied thisphenomenon and its physiological basis in eight New Zealand Whiterabbits that were anesthetized, paralyzed, and mechanically ventilatedat a fixed minute ventilation. Isovolemic anemia was induced bysimultaneous blood withdrawal and infusion of 6% hetastarch insequential stages; exchange transfusions ranged from 15-30 ml involume. Variables measured after each hemodilution included hematocrit(Hct), arterial and venous blood gases, mixed expiredPCO₂ andPO₂, and blood pressure; also, O₂ consumption,CO₂ production, cardiac output(), and physiological dead space were calculated.Data were analyzed by comparison of changes in variables with changesin Hct and by using the model of capillary gas exchange described byBidani (J. Appl. Physiol. 70:1686-1699, 1991). There was complete compensation for anemia withstability of venous and arterial PCO₂between Hct values of 36 ± 3 and 12 ± 1%, which was predictedby the mathematical model. Over this range of hemodilution, rose 50%, and theO₂ extraction ratio increased 61%without a decline in CO₂production or a rise in alveolar ventilation. The dominantcompensations maintaining CO₂transport in normovolemic anemia include an increased and an augmented Haldane effect arising from theaccompanying greater O₂extraction.

     

Appropriate thermal manipulations eliminate tremors in rats recovering from halothane anesthesia

Grahn, D. A., M. C. Heller, J. E. Larkin, and H. C. Heller.Appropriate thermal manipulations eliminate tremors in ratsrecovering from halothane anesthesia. J. Appl.Physiol. 81(6): 2547-2554, 1996.Tremors arecommon in mammals emerging from anesthesia. To determine whetherappropriate thermal manipulations immediately before emergence fromanesthesia are sufficient to eliminate these tremors,electroencephalographic (EEG) and electromyographic (EMG) activities,hypothalamic temperature (T_hy),and O₂ consumption were monitoredin 12 rats recovering from halothane anesthesia under three thermalregimes. EEG and EMG activities were recorded throughout anesthesia andserved as feedback signals for controlling anesthetic depth. Duringanesthesia, T_hy was either1) allowed to fall to32-34°C, 2) maintained at37-39°C, or 3) allowed to fall to 32-34°C and then raised to 37-39°C. Whenhypothermic on emergence from anesthesia, all of the animals exhibitedpostanesthetic tremors that persisted untilT_hy values returned tonormothermia. None of the animals expressed postanesthetic tremors whennormothermic on emergence from anesthesia. In addition, the timebetween emergence from anesthesia (as determined by EEG/EMG parameters)and the initiation of coordinated motor activities was significantlydecreased in the normothermic animals.