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.

     

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.

     

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.

     

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.

     

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.

     

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.

     

Ventilatory response to exercise in subjects breathing CO2 or HeO2

Babb, T. G. Ventilatory response to exercise insubjects breathing CO₂ orHeO₂.J. Appl. Physiol. 82(3): 746-754, 1997.To investigate the effects of mechanical ventilatory limitationon the ventilatory response to exercise, eight older subjects with normal lung function were studied. Each subject performed graded cycleergometry to exhaustion once while breathing room air; once whilebreathing 3% CO₂-21%O₂-balanceN₂; and once while breathing HeO₂ (79% He and 21%O₂). Minute ventilation(E) and respiratory mechanics weremeasured continuously during each 1-min increment in work rate (10 or20 W). Data were analyzed at rest, at ventilatory threshold (VTh),and at maximal exercise. When the subjects were breathing 3%CO₂, there was an increase(P < 0.001) inE at rest and at VTh but not duringmaximal exercise. When the subjects were breathingHeO₂,E was increased(P < 0.05) only during maximalexercise (24 ± 11%). The ventilatory response to exercise belowVTh was greater only when the subjects were breathing 3% CO₂(P < 0.05). Above VTh, theventilatory response when the subjects were breathingHeO₂ was greater than whenbreathing 3% CO₂(P < 0.01). Flow limitation, aspercent of tidal volume, during maximal exercise was greater(P < 0.01) when the subjects werebreathing CO₂ (22 ± 12%) thanwhen breathing room air (12 ± 9%) or when breathingHeO₂ (10 ± 7%)(n = 7). End-expiratory lung volumeduring maximal exercise was lower when the subjects were breathingHeO₂ than when breathing room airor when breathing CO₂(P < 0.01). These data indicate thatolder subjects have little reserve for accommodating an increase inventilatory demand and suggest that mechanical ventilatory constraintsinfluence both the magnitude of Eduring maximal exercise and the regulation ofE and respiratory mechanics duringheavy-to-maximal exercise.

     

Sodium alterations in isolated rat heart during cardioplegic arrest

Schepkin, V. D., I. O. Choy, and T. F. Budinger. Sodiumalterations in isolated rat heart during cardioplegic arrest. J. Appl. Physiol. 81(6):2696-2702, 1996.Triple-quantum-filtered (TQF) Na nuclearmagnetic resonance (NMR) without chemical shift reagent is used toinvestigate Na derangement in isolated crystalloid perfused rat heartsduring St. Thomas cardioplegic (CP) arrest. Theextracellular Na contribution to the NMR TQF signal of a rat heart isfound to be 73 ± 5%, as determined by wash-out experiments atdifferent moments of ischemia and reperfusion. With the use of thiscontribution factor, the estimated intracellular Na([Na⁺]_i)TQF signal is 222 ± 13% of preischemic level after 40 min of CParrest and 30 min of reperfusion, and the heart rate pressure productrecovery is 71 ± 8%. These parameters aresignificantly better than for stop-flow ischemia: 340 ± 20% and 6 ± 3%, respectively. At 37°C, the initial delay of 15 min in[Na⁺]_igrowth occurs during CP arrest along with reduced growth later (~4.0%/min) in comparison with stop-flow ischemia (~6.7%/min). The hypothermia (21°C, 40 min) for the stop-flow ischemia and CPdramatically decreases the[Na⁺]_igain with the highest heart recovery for CP (~100%). These studiesconfirm the enhanced sensitivity of TQF NMR to[Na⁺]_iand demonstrate the potential of NMR without chemical shift reagent tomonitor[Na⁺]_iderangements.

     

Fetal sheep adrenal blood flow responses to hypoxemia after splanchnicotomy using fluorescent microspheres

Buchwalder, Lynn F., Michelle Lin, Thomas J. McDonald, andPeter W. Nathanielsz. Fetal sheep adrenal blood flow responses tohypoxemia after splanchnicotomy using fluorescent microspheres. J. Appl. Physiol. 84(1): 82-89, 1998.Adrenal gland blood flow (ABF) increases during hypoxemia infetal sheep, but regulation of ABF is poorly understood. The purpose ofthis study was to determine the effects of splanchnic nerve section onfetal ABF responses to hypoxemia using the fluorescent microsphere (FM) technique. At 125 days of gestation, 14 unanesthetized fetal sheep [bilateral splanchnicotomy (Splx,n = 6) and control (Cont,n = 8)] were injectedwith FM before and at 60 min ofN₂-induced hypoxemia (~40%decrease in fetal arterial PO₂).Adrenal tissue and reference blood samples were digested and filtered, and FM dye was extracted for spectrometer analysis. Baseline whole, medullary, and cortical ABF for the Cont group were similar to published values using radioactive microspheres and did not differ fromSplx values. Hypoxemia increased whole, medullary, and cortical ABF(mean ± SE) from baseline for the Cont group by 281 ± 35, 258 ± 31, and 496 ± 81% (P < 0.05). The increase for the Splx group was attenuated compared with theCont group (P < 0.05) for whole andmedullary ABF (139 ± 27 and 43 ± 27%) but not cortical ABF(326 ± 91%). We conclude that1) the FM technique is valid formeasuring fetal ABF and 2) in fetalsheep the splanchnic nerve is not necessary to maintain basal ABF butplays an important role in regulating the hypoxemia-induced increase inABF through the medullary, but not cortical, ABF response.

     

Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women

Brooks, E. M., A. L. Morgan, J. M. Pierzga, S. L. Wladkowski, J. T. O'Gorman, J. A. Derr, and W. L. Kenney. Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women. J. Appl.Physiol. 83(2): 477-484, 1997.This investigationexamined effects of chronic (2 yr) hormone replacement therapy (HRT),both estrogen replacement therapy (ERT) and estrogen plus progesteronetherapy (E+P), on core temperature and skin blood flow responses ofpostmenopausal women. Twenty-five postmenopausal women [9 not onHRT (NO), 8 on ERT, 8 on E+P] exercised on a cycle ergometer for1 h at an ambient temperature of 36°C. Cutaneous vascularconductance (CVC) was monitored by laser-Doppler flowmetry, and forearmvascular conductance (FVC) was measured by using venous occlusionplethysmography. Iontophoresis of bretylium tosylate was performedbefore exercise to block local vasoconstrictor (VC) activity at oneskin site on the forearm. Rectal temperature (T_re) was ~0.5°C lower forthe ERT group (P < 0.01) comparedwith E+P and NO groups at rest and throughout exercise. FVC: mean body temperature (T_b) and CVC:T_b curves were shifted~0.5°C leftward for the ERT group(P < 0.0001). Baseline CVC wassignificantly higher in the ERT group(P < 0.05), but there was nointeraction between bretylium treatment and groups once exercise wasinitiated. These results suggest that1) chronic ERT likely acts centrally to decrease T_re,2) ERT lowers theT_re at which heat-loss effector mechanisms are initiated, primarily by actions on active cutaneous vasodilation, and 3) addition ofexogenous progestins in HRT effectively blocks these effects.

     

Ventilatory stability to transient CO2 disturbances in hyperoxia and normoxia in awake humans

Lai, Jie, and Eugene N. Bruce. Ventilatory stability totransient CO₂ disturbances inhyperoxia and normoxia in awake humans. J. Appl.Physiol. 83(2): 466-476, 1997.Modarreszadeh andBruce (J. Appl. Physiol. 76:2765-2775, 1994) proposed that continuous random disturbances inarterial PCO₂ are more likely toelicit ventilatory oscillation patterns that mimic periodic breathingin normoxia than in hyperoxia. To test this hypothesis experimentally,in nine awake humans we applied pseudorandom binary inspiredCO₂ fraction stimulation innormoxia and hyperoxia to derive the closed-loop and open-loopventilatory responses to a briefCO₂ disturbance in terms ofimpulse responses and transfer functions. The closed-loop impulseresponse has a significantly higher peak value [0.143 ± 0.071 vs. 0.079 ± 0.034 (SD)l · min¹ · 0.01 lCO₂¹,P = 0.014] and a significantlyshorter 50% response duration (42.7 ± 13.3 vs. 72.3 ± 27.6 s,P = 0.020) in normoxia than in hyperoxia. Therefore, the ventilatory responses to transientCO₂ disturbances are less damped(but generally not oscillatory) in normoxia than in hyperoxia. For theclosed-loop transfer function, the gain in normoxia increasedsignificantly (P < 0.0005), while phase delay decreased significantly (P < 0.0005). The gain increased by 108.5, 186.0, and 240.6%, whilephase delay decreased by 26.0, 18.1, and 17.3%, at 0.01, 0.03, and0.05 Hz, respectively. Changes in the same direction were found for theopen-loop system. Generally, an oscillatory ventilatory response to asmall transient CO₂ disturbance isunlikely during wakefulness. However, changes in parameters that leadto additional increases in chemoreflex loop gain are more likely toinitiate oscillations in normoxia than in hyperoxia.

     

Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis

Hsia, C. C. W., C. J. C. Chuong, and R. L. Johnson, Jr.Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis. J. Appl.Physiol. 83(4): 1397-1404, 1997.To understandthe effects of dynamic shape distortion of red blood cells (RBCs) as itdevelops under high-flow conditions on the standard physiological andmorphometric methods of estimating pulmonary diffusing capacity, wecomputed the uptake of CO across a two-dimensional geometric capillarymodel containing a variable number of equally spaced RBCs. RBCs arecircular or parachute shaped, with the same perimeter length. Total COdiffusing capacity (DL_CO)and membrane diffusing capacity(DM_CO)were calculated by a finite element method.DL_COcalculated at two levels of alveolar PO₂ were used to estimateDM_CO by theRoughton-Forster (RF) technique. The same capillary model was subjectedto morphometric analysis by the random linear intercept method toobtain morphometric estimates ofDM_CO. Results show thatshape distortion of RBCs significantly reduces capillary diffusive gasuptake. Shape distortion exaggerates the conceptual errors inherent inthe RF technique (J. Appl. Physiol.79: 1039-1047, 1995); errors are exaggerated at a high capillaryhematocrit. Shape distortion also introduces additional error inmorphometric estimates ofDM_CO causedby a biased sampling distribution of random linear intercepts; errors are exaggerated at a low capillary hematocrit.