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.

     

Raising P50 increases tissue PO2 in canine skeletal muscle but does not affect critical O2 extraction ratio

Curtis, Scott E., Thomas A. Walker, W. E. Bradley, andStephen M. Cain. Raising P₅₀increases tissue PO₂ in canineskeletal muscle but does not affect criticalO₂ extraction ratio.J. Appl. Physiol. 83(5):1681-1689, 1997.Affinity of hemoglobin (Hb) forO₂ determines in part the rate ofO₂ diffusion from capillaries tomyocytes by altering capillary PO₂.We hypothesized that a decrease in HbO₂ affinity (increasedP₅₀) would increase capillary and tissue PO₂(Pti_O2) andimprove O₂ consumption duringischemia. To test this hypothesis, blood flow to the pump-perfused lefthindlimb of 18 anesthetized and paralyzed dogs was progressively decreased over 90 min while hindlimb O₂ consumption andO₂ delivery (O₂)and Pti_O2 weremeasured at the muscle surface. Arterial PO₂ was maintained at 150 ± 10 Torr in all dogs. We increased P₅₀by 12.3 ± 0.9 (SE) Torr in nine dogs with RSR-13, an allosteric modifier of Hb. This decreased arterialO₂ saturation to 90-92% butincreased meanPti_O2 from 35.5 ± 11.6 to 44.1 ± 15.2 (SD) Torr(P < 0.05) with no change incontrols (n = 9).O₂ extraction ratio at criticalO₂was 74 ± 2% in controls and 79 ± 1% in RSR-13-treated dogs(P = not significant).Pti_O2 was30-40% higher in the RSR-13-treated group at anyO₂above critical but did not differ between groups below criticalO₂.Perfusion heterogeneity and convergence of the dissociation curvesnear criticalO₂ may have mitigated any effect of increasedP₅₀ onO₂ diffusion. Still, increasingP₅₀ by 12 Torr with RSR-13significantly increased Pti_O2 atO₂values above critical.

     

Metabolic and phenotypic adaptations of diaphragm muscle fibers with inactivation

Zhan, Wen-Zhi, Hirofumi Miyata, Y. S. Prakash, and Gary C. Sieck. Metabolic and phenotypic adaptations of diaphragm musclefibers with inactivation. J. Appl.Physiol. 82(4):1145-1153, 1997.We hypothesizedthat metabolic adaptations to muscle inactivity are most pronouncedwhen neurotrophic influence is disrupted. In ratdiaphragm muscle(Dia_m), 2 wk ofunilateral denervation or tetrodotoxin nerve blockade resulted in areduction in succinate dehydrogenase (SDH) activity of type I, IIa, andIIx fibers (~50, 70, and 24%, respectively) and a decrease in SDHvariability among fibers (~63%). In contrast, inactivity induced byspinal cord hemisection at C₂ (ST)resulted in much less change in SDH activity of type I and IIa fibers(~27 and 24%, respectively) and only an ~30% reduction in SDHvariability among fibers. Actomyosin adenosinetriphosphatase (ATPase)activities of type I, IIx, and IIb fibers in denervated andtetrodotoxin-treated Dia_m werereduced by ~20, 45, and 60%, respectively, and actomyosin ATPasevariability among fibers was ~60% lower. In contrast, onlyactomyosin ATPase activity of type IIb fibers was reduced (~20%) inST Dia_m. These results suggestthat disruption of neurotrophic influence has a greater impact onmuscle fiber metabolic properties than inactivity per se.

     

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).

     

Effects of N2O narcosis on breathing and effort sensations during exercise and inspiratory resistive loading

Fothergill, D. M., and N. A. Carlson. Effects ofN₂O narcosis on breathing andeffort sensations during exercise and inspiratory resistive loading.J. Appl. Physiol. 81(4):1562-1571, 1996.The influence of nitrous oxide(N₂O) narcosis on the responses toexercise and inspiratory resistive loading was studied in thirteen maleUS Navy divers. Each diver performed an incremental bicycle exercisetest at 1 ATA to volitional exhaustion while breathing a 23%N₂O gas mixture and a nonnarcoticgas of the same PO₂, density, andviscosity. The same gas mixtures were used during four subsequent30-min steady-state submaximal exercise trials in which the subjectsbreathed the mixtures both with and without an inspiratory resistance(5.5 vs. 1.1 cmH₂O ^· s ^· l¹at 1 l/s). Throughout each test, subjective ratings of respiratory effort (RE), leg exertion, and narcosis were obtained with acategory-ratio scale. The level of narcosis was rated between slightand moderate for the N₂O mixturebut showed great individual variation. Perceived leg exertion and thetime to exhaustion were not significantly different with the twobreathing mixtures. Heart rate was unaffected by the gas mixture andinspiratory resistance at rest and during steady-state exercise but wassignificantly lower with the N₂O mixture during incremental exercise (P < 0.05). Despite significant increases in inspiratory occlusionpressure (13%; P < 0.05),esophageal pressure (12%; P < 0.001), expired minute ventilation (4%;P < 0.01), and the work rate ofbreathing (15%; P < 0.001) when the subjects breathed the N₂O mixture,RE during both steady-state and incremental exercise was 25% lowerwith the narcotic gas than with the nonnarcotic mixture(P < 0.05). We conclude that the narcotic-mediated changes in ventilation, heart rate, and RE induced by23% N₂O are not of sufficientmagnitude to influence exercise tolerance at surface pressure.Furthermore, the load-compensating respiratory reflexes responsible formaintaining ventilation during resistive breathing are not depressed byN₂O narcosis.

     

Thromboxane A2 mediates increased pulmonary microvascular permeability after intestinal reperfusion

Turnage, Richard H., John L. LaNoue, Kevin M. Kadesky, YanMeng, and Stuart I. Myers. ThromboxaneA₂ mediates increased pulmonarymicrovascular permeability after intestinal reperfusion. J. Appl. Physiol. 82(2): 592-598, 1997.This study examines the hypothesis that intestinal reperfusion(IR)-induced pulmonary thromboxane A₂(TxA₂) release increases localmicrovascular permeability and induces pulmonary vasoconstriction.Sprague-Dawley rats underwent 120 min of intestinal ischemia and 60 minof IR. Sham-operated animals (Sham) served as controls. After IR orSham, the pulmonary vessels were cannulated, and the lungs wereperfused in vitro with Krebs buffer. Microvascular permeability wasquantitated by determining the filtration coefficient(K_f),and pulmonary arterial (Ppa), venous (Ppv), and capillary (Ppc)pressures were measured to calculate vascular resistance (Rt). Afterbaseline measurements, imidazole(TxA₂ synthase inhibitor) orSQ-29,548 (TxA₂-receptorantagonist) was added to the perfusate; thenK_f, Ppa, Ppv, and Ppc were again measured. TheK_fof lungs from IR animals was four times greater than that of Sham(P = 0.001), and Rt was 63% greaterin the injured group (P = 0.01). Pc of IR lungs was twice that of controls (5.4 ± 1.0 vs. 2.83 ± 0.3 mmHg, IR vs. Sham, respectively; P < 0.05). Imidazole or SQ-29,548 returnedK_fto baseline measurements (P < 0.05)and reduced Rt by 23 and 17%, respectively(P < 0.05). IR-induced increases in Pc were only slightly reduced by 500 µg/ml imidazole (14%;P = 0.05) but unaffected by lowerdoses of imidazole (5 or 50 µg/ml) or SQ-29,548. These data suggestthat IR-induced pulmonary edema is caused by both increasedmicrovascular permeability and increased hydrostatic pressure and thatthese changes are due, at least in part, to the ongoing release ofTxA₂.

     

Dehydration markedly impairs cardiovascular function in hyperthermic endurance athletes during exercise

González-Alonso, José, RicardoMora-Rodríguez, Paul R. Below, and Edward F. Coyle.Dehydration markedly impairs cardiovascular function inhyperthermic endurance athletes during exercise. J. Appl. Physiol. 82(4): 1229-1236, 1997.Weidentified the cardiovascular stress encountered by superimposingdehydration on hyperthermia during exercise in the heat and themechanisms contributing to the dehydration-mediated stroke volume (SV)reduction. Fifteen endurance-trained cyclists [maximalO₂ consumption(O_{2 max}) = 4.5 l/min] exercised in the heat for 100-120 min and either became dehydrated by 4% body weight or remained euhydrated by drinkingfluids. Measurements were made after they continued exercise at 71%O_{2 max} for 30 minwhile 1) euhydrated with anesophageal temperature (T_es) of38.1-38.3°C (control); 2)euhydrated and hyperthermic (39.3°C);3) dehydrated and hyperthermic withskin temperature (T_sk) of34°C; 4) dehydrated withT_es of 38.1°C and T_sk of 21°C; and5) condition4 followed by restored blood volume. Compared withcontrol, hyperthermia (1°C T_esincrease) and dehydration (4% body weight loss) each separatelylowered SV 7-8% (11 ± 3 ml/beat;P < 0.05) and increased heart ratesufficiently to prevent significant declines in cardiac output.However, when dehydration was superimposed on hyperthermia, thereductions in SV were significantly (P < 0.05) greater (26 ± 3 ml/beat), and cardiac output declined 13% (2.8 ± 0.3 l/min). Furthermore, mean arterialpressure declined 5 ± 2%, and systemic vascular resistanceincreased 10 ± 3% (both P < 0.05). When hyperthermia wasprevented, all of the decline in SV with dehydration was due to reducedblood volume (~200 ml). These results demonstrate that thesuperimposition of dehydration on hyperthermia during exercise in theheat causes an inability to maintain cardiac output and blood pressurethat makes the dehydrated athlete less able to cope with hyperthermia.

     

Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction

Charan, Nirmal B., and Paula Carvalho. Angiogenesis inbronchial circulatory system after unilateral pulmonary artery obstruction. J. Appl. Physiol. 82(1):284-291, 1997.We studied the effects of left pulmonary artery(LPA) ligation on the bronchial circulatory system (BCS) by using asheep model. LPA was ligated in the newborn lambs soon after birth(n = 8), and when the sheep were ~3yr of age anatomic studies revealed marked angiogenesis in BCS.Bronchial blood flow and cardiac output were studied by placing flowprobes around the bronchial and pulmonary arteries in four adult sheep.After LPA ligation, bronchial blood flow increased from 35 ± 6 to134 ± 42 ml/min in ~3 wk (P < 0.05). We also studied gas-exchange functions of BCS ~3 yr after the ligation of LPA in newborn lambs (n = 4) and used a control group (n = 12)in which LPA was ligated acutely. In the left lung,O₂ uptake after acute ligation was16 ± 3 ml/min and was similar to the chronic model, whereasCO₂ output in the control group was 27 ± 3 ml/min compared with 79 ± 12 ml/min in the chronic preparation (P < 0.05).We conclude that LPA ligation causes marked angiogenesis in BCS that iscapable of performing some gas-exchange functions.

     

Ventilation distribution during histamine provocation

Verbanck, S., D. Schuermans, A. Van Muylem, M. Paiva, M. Noppen, and W. Vincken. Ventilation distribution during histamine provocation. J. Appl. Physiol. 83(6):1907-1916, 1997.We investigated ventilation inhomogeneity duringprovocation with inhaled histamine in 20 asymptomatic nonsmokingsubjects. We used N₂multiple-breath washout (MBW) to deriveparameters S_condand S_acin as ameasurement of ventilation inhomogeneity in conductive and acinar zonesof the lungs, respectively. A 20% decrease of forced expiratory volume in 1 s (FEV₁) was used todistinguish responders from nonresponders. In the responder group,average FEV₁ decreased by 26%,whereas S_condincreased by 390% with no significant change inS_acin. In thenonresponder group, FEV₁ decreasedby 11%, whereasS_cond increased by 198% with no significantS_acin change.Despite the absence of change inS_acin duringprovocation, baselineS_acin wassignificantly larger in the responder vs. the nonresponder group. Themain findings of our study are that during provocation largeventilation inhomogeneities occur, that the small airways affected bythe provocation process are situated proximal to the acinar zone wherethe diffusion front stands, and that, in addition to overall decreasein airway caliber, there is inhomogeneous narrowing of parallelairways.

     

Inhibition of allergic airway responses by inhaled low-molecular-weight heparins: molecular-weight dependence

Martinez-Salas, José, Richard Mendelssohn, William M. Abraham, Bernard Hsiao, and Tahir Ahmed. Inhibition of allergic airway responses by inhaled low-molecular-weight heparins:molecular-weight dependence. J. Appl.Physiol. 84(1): 222-228, 1998.Inhaled heparin prevents antigen-induced bronchoconstriction and inhibitsanti-immunoglobulin E-mediated mast cell degranulation. We hypothesizedthat the antiallergic action of heparin may be molecular weightdependent. Therefore, we studied the effects of three differentlow-molecular-weight fractions of heparin [medium-, low-, andultralow-molecular-weight heparin (MMWH, LMWH, ULMWH,respectively)] on the antigen-induced acute bronchoconstrictorresponse (ABR) and airway hyperresponsiveness (AHR) in allergic sheep.Specific lung resistance was measured in 22 sheep before and afterairway challenge with Ascarissuum antigen, without and afterpretreatment with inhaled fractionated heparins at doses of0.31-5.0 mg/kg. Airway responsiveness was estimated before and 2 hpostantigen as the cumulative provocating dose of carbachol in breathunits that increased specific lung resistance by 400%. Allfractionated heparins caused a dose-dependent inhibition of ABR andAHR. ULMWH was the most effective fraction, with the inhibitory dosecausing 50% protection (ID₅₀)against ABR of 0.5 mg/kg, whereasID₅₀ values of LMWH and MMWH were1.25 and 1.8 mg/kg, respectively. ULMWH was also the most effective fraction in attenuating AHR; theID₅₀ values for ULMWH, LMWH, andMMWH were 0.5, 2.5, and 4.7 mg/kg, respectively. These data suggestthat 1) fractionatedlow-molecular-weight heparins attenuate antigen-induced ABR and AHR;2) there is an inverse relationship between the antiallergic activity of heparin fractions and molecular weight; and 3) ULMWH is the mosteffective fraction preventing allergic bronchoconstriction and airwayhyperresponsiveness.

     

Passive sensitization of human airways induces myogenic contractile responses in vitro

Mitchell, R. W., K. F. Rabe, H. Magnussen, and A. R. Leff.Passive sensitization of human airways induces myogenic contractile responses in vitro. J. Appl.Physiol. 83(4): 1276-1281, 1997.We assessedeffects of passive sensitization on human bronchial smooth muscle (BSM)response to mechanical stretching in vitro. Bronchial rings were sham(control) or passively sensitized overnight by using sera from donorsdemonstrating sensitivity to Dermatophagoides farinae and having immunoglobulin E (IgE)concentrations of 2,600 ± 200 U/ml. Tissues were fixedisometrically to force transducers to measure responses to electricalfield stimulation (EFS) and quick stretch (QS). The myogenic responseto QS was normalized to the maximal response to EFS (%EFS). Themyogenic response of sensitized BSM was 47.9 ± 10.9 %EFS to a QSof ~6.5% optimal length (L_o);sham-sensitized tissues had a myogenic response of 13.5 ± 6.4 %EFS(P = 0.012 vs. passively sensitized).A QS of ~13% L_o in sensitizedBSM caused a response of 82.8 ± 20.9 %EFS; sham-sensitized tissuesdeveloped a response of 38.2 ± 17.3 %EFS(P = 0.004). BSM incubated with serumfrom nonallergic donors did not demonstrate increased QS response (4.6 ± 1.4 %EFS, P = not significantvs. tissue exposed to atopic sera). However, tissues incubated in serafrom nonatopic donors supplemented with hapten-specific chimeric IgE(JW8) demonstrated augmented myogenic response to QS of ~6.5% L_o (21.9 ± 6.2 %EFS, P = 0.027 vs. nonatopicsera alone). We demonstrate that passive sensitization of human BSMpreparations causes induction and augmentation of myogenic contractionsto QS; this hyperresponsiveness corresponds to the IgE concentration insensitizing sera.

     

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.

     

Decompression comparison of helium and hydrogen in rats

Lillo, R. S., E. C. Parker, and W. R. Porter.Decompression comparison of helium and hydrogen in rats.J. Appl. Physiol. 82(3): 892-901, 1997.The hypothesis that there are differences in decompression riskbetween He and H₂ wasexamined in 1,607 unanesthetized male albino rats subjected to dives on2% O₂-balance He or 2%O₂-balanceH₂ (depths  50 ATA, bottom times  60 min). The animals were decompressed to 10.8 ATA with profilesvarying from rapid to slow, with up to four decompression stops of up to 60 min each. Maximum likelihood analysis was used to estimate therelative decompression risk on a per unit pressure basis (termed "potency") and the rate of gas uptake and elimination, bothfactors affecting the decompression sickness risk, from a specific dive profile. H₂ potency for causingdecompression sickness was found to be up to 35% greater than that forHe. Uptake rates were unresolvable between the two gases with the timeconstant (TC) estimated at ~2-3 min, leading to saturation inboth cases in <15 min. Washout of both gases was significantly slowerthan uptake, with He washout (TC ~1.5-3 h) substantially slowerthan H₂ washout (TC ~0.5 h). Itis unknown whether the decompression advantage of the faster washout ofH₂ or the disadvantage of itsincreased potency, observed in the rat, would be important for humandiving.

     

Diaphragm thickening during inspiration

Cohn, David, Joshua O. Benditt, Scott Eveloff, and F. DennisMcCool. Diaphragm thickening during inspiration.J. Appl. Physiol. 83(1): 291-296, 1997.Ultrasound has been used to measure diaphragm thickness(T_di) in thearea where the diaphragm abuts the rib cage (zone of apposition).However, the degree of diaphragm thickening during inspiration reportedas obtained by one-dimensional M-mode ultrasound was greater than thatpredicted by using other radiographic techniques. Becausetwo-dimensional (2-D) ultrasound provides greater anatomic definitionof the diaphragm and neighboring structures, we used this technique toreevaluate the relationship between lung volume andT_di. We firstestablished the accuracy and reproducibility of 2-D ultrasound bymeasuring T_diwith a 7.5-MHz transducer in 26 cadavers. We found thatT_di measured byultrasound correlated significantly with that measured by ruler (R² = 0.89), withthe slope of this relationship approximating a line of identity(y = 0.89x + 0.04 mm). The relationship between lung volume andT_di was thenstudied in nine subjects by obtaining diaphragm images at the fivetarget lung volumes [25% increments from residual volume (RV) tototal lung capacity (TLC)]. Plots ofT_di vs. lungvolume demonstrated that the diaphragm thickened as lung volumeincreased, with a more rapid rate of thickening at the higher lungvolumes[T_di = 1.74 vital capacity (VC)² + 0.26 VC + 2.7 mm] (R² = 0.99; P < 0.001) where lung volumeis expressed as a fraction of VC. The mean increase inT_di between RVand TLC for the group was 54% (range 42-78%). We conclude that2-D ultrasound can accurately measureT_di and that theaverage thickening of the diaphragm when a subject is inhaling from RVto TLC using this technique is in the range of what would be predictedfrom a 35% shortening of the diaphragm.

     

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.

     

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.

     

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.

     

Mechanical impedance of the lung periphery

Hantos, Z., F. Peták, Á. Adamicza, T. Asztalos, J. Tolnai, and J. J. Fredberg. Mechanical impedance ofthe lung periphery. J. Appl. Physiol.83(5): 1595-1601, 1997.The mechanics of the regional airways andtissues was studied in isolated dog lobes by means of a modifiedwave-tube technique. Small-amplitude pseudorandom forced oscillationsbetween 0.1 and 48 Hz were applied through catheters wedged in2-mm-diameter bronchi in three regions of each lobe at translobarpressures (PL) of 10, 7, 5, 3, 2, and 1 cmH₂O. The measuredregional input impedances were fitted by a model containing theresistance (R₁) and inertance(I) of the regular (segmental) airways, the resistance of thecollateral channels (R₂), andthe damping (G) and elastance (H) of the local tissues. This model gavefar better fits to the data on impedance of the lung periphery thanwhen G and H were replaced by a single tissue compliance, whichexplains why interruption of segmental flow did not lead tomonoexponential pressure decay in previous studies. The interlobar andintralobar variances of the parameters were equally significant, andpoor correlations were found between the airway parametersR₁ andR₂ and between any airway andtissue parameter (e.g., R₁ and H).R₂ was on average ~10 timeshigher than R₁, although theR₂-to-R₁ratios and their dependencies on PL were regionally highlyvariable. However, for the total of 33 regions studied, thePL dependence was the same forR₁ and R₂, which may reflect similarmorphological structures for the regular and collateral airways. Thedependencies of G and H on PLshowed high interregional variations; generally, however, they assumedtheir minima at medium PL values(~5 cmH₂O).

     

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.

     

Capillary and arteriolar responses to local vasodilators are impaired in a rat model of sepsis

Although sepsis isknown to affect vascular function, little is known about changes at thecapillary level. We hypothesized that sepsis attenuates the"upstream" arteriolar response to vasoactive agents appliedlocally to capillaries. Sepsis in rats was induced by cecal ligationand perforation. After 24 h, extensor digitorum longus muscle wasprepared for intravital microscopy. Phenylephrine (PE, 10 mM) andacetylcholine (ACh, 10 mM) were applied iontophoretically on terminalarterioles and on their downstream daughter capillaries (300 µm fromarteriole). There was no significant difference between control andseptic rats in baseline arteriolar diameters [8.0 ± 0.6 vs.9.8 ± 0.8 (SE) µm] or baseline red blood cellvelocity (V_RBC)in perfused daughter capillaries (255 ± 10 vs. 264 ± 13 µm/s). Application of PE onto arterioles resulted in comparable constrictions (i.e., 22% diameter change) andV_RBC reductions (100%) in control and septic rats. In contrast, arteriolardiameter and V_RBCincreases after application of ACh were attenuated in sepsis (diameter:from 41 to 14%;V_RBC: from 67 to24%). Application of PE onto the capillary reducedV_RBC to the samelevel (100%) in both groups, whereas application of AChincreased V_RBCless in septic than in control rats (20 vs. 73%). On the basis ofarteriolar-capillary pair stimulations, sepsis affectedV_RBC responses toACh more in the capillary than in the arteriole. When the adenosineanalog 5'-N-ethylcarboxamidoadenosine(0.1 mM) was used instead of ACh, similar effects of sepsis were seen.To test for a possible involvement of inducible NO synthase (iNOS) insepsis-induced attenuated ACh responses, arterioles and capillaries inseptic animals were locally pretreated with the iNOS blockeraminoguanidine (10 mM). In both microvessels, aminoguanidine restoredthe ACh response to the control level. We conclude that impairedcapillary V_RBCand arteriolar diameter responses to vasodilators applied tocapillaries in septic rat skeletal muscle were due to dysfunction atarteriolar and capillary levels. The study underscores the significantrole iNOS/NO may play in sepsis-induced alteration of vascularreactivity in vivo.