Involvement of the fastigial nuclei in vagally mediated respiratory responses

Xu, Fadi, and Donald T. Frazier. Involvement of thefastigial nuclei in vagally mediated respiratory responses.J. Appl. Physiol. 82(6):1853-1861, 1997.Previous studies have demonstrated that thecerebellum, especially the fastigial nucleus (FN), is capable ofmodulating respiratory responses to chemical and mechanical stimuli.Because there is evidence to show projections from vagal afferents tothe FN, the goal of this study was to determine the role of the FN inthe respiratory reflexes elicited by activation of vagal afferents.Experiments were performed in anesthetized (chloralose), paralyzed, andartificially ventilated cats with an occipital exposure of thecerebellum. Administration of capsaicin (Cap; 5-10 µg/kg) viathe right external jugular vein at the end of inspiration andapplication of lung inflation (LI; 10 cmH₂O) during inspiration werecarried out to stimulate nonmyelinated and myelinated vagal afferents,respectively. The phrenic neurogram was recorded as anindex of the respiratory motor output. Control cardiorespiratoryvariables [expiratory duration(TE), arterial bloodpressure] and their immediate responses to stimuli were comparedbefore and after bilateral lesions of the FN. The results showed thefollowing. 1) Capinjection and LI resulted in a dramatic increase inTE (apnea).2) FN lesions did not significantlyalter the control TE; however,the apneic duration induced by Cap injection was prolonged.3) Neither FN lesions norcerebellectomy affected the apneic duration that resulted fromapplication of LI. 4) Cold blockadeof the vagi (6-8°C) eliminated the respiratory responses elicited by LI but not Cap injection; vagotomy abolished the responses to both stimuli. 5) FN lesions didnot change the control ABP or its responses to either LI or Capinjection. It is concluded that the FN is involved in vagally mediatedrespiratory reflexes elicited by activation of nonmyelinated (C-fiber)vagal afferents.

     

Effect of prior O2 breathing on ventilatory response to sustained isocapnic hypoxia in adult humans

Honda, Y., H. Tani, A. Masuda, T. Kobayashi, T. Nishino, H. Kimura, S. Masuyama, and T. Kuriyama. Effect of priorO₂ breathing on ventilatoryresponse to sustained isocapnic hypoxia in adult humans.J. Appl. Physiol. 81(4):1627-1632, 1996.Sixteen healthy volunteers breathed 100%O₂ or room air for 10 min in random order, then their ventilatory response to sustained normocapnic hypoxia (80% arterial O₂saturation, as measured with a pulse oximeter) was studied for 20 min.In addition, to detect agents possibly responsible for the respiratorychanges, blood plasma of 10 of the 16 subjects was chemically analyzed.1) Preliminary O₂ breathing uniformly andsubstantially augmented hypoxic ventilatory responses.2) However, the profile ofventilatory response in terms of relative magnitude, i.e., biphasichypoxic ventilatory depression, remained nearly unchanged.3) Augmented ventilatory incrementby prior O₂ breathing wassignificantly correlated with increment in the plasma glutamine level.We conclude that preliminary O₂administration enhances hypoxic ventilatory response without affectingthe biphasic response pattern and speculate that the excitatory aminoacid neurotransmitter glutamate, possibly derived from augmentedglutamine, may, at least in part, play a role in this ventilatoryenhancement.

     

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).

     

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

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

     

Mechanical advantage of the canine triangularis sterni

De Troyer, André, and Alexandre Legrand.Mechanical advantage of the canine triangularis sterni.J. Appl. Physiol. 84(2): 562-568, 1998.Recent studies on the canine parasternal intercostal,sternomastoid, and scalene muscles have shown that the maximal changesin airway opening pressure (Pao) obtained per unit muscle mass(Pao/m) during isolatedcontraction are closely related to the fractional changes in musclelength per unit volume increase of the relaxed chest wall. In thepresent study, we have examined the validity of this relationship for the triangularis sterni, an important expiratory muscle of the rib cagein dogs. Passive inflation above functional residual capacity (FRC)induced a virtually linear increase in muscle length, such that, with a1.0-liter inflation, the muscle lengthened by 17.9 ± 1.6 (SE) % of its FRC length. When the muscle in one interspace wasmaximally stimulated at FRC, Pao increased by 0.84 ± 0.11 cmH₂O. However, in agreement withthe length-tension characteristics of the muscle, when lung volume wasincreased by 1.0 liter before stimulation, the rise in Pao amounted to1.75 ± 0.12 cmH₂O. At thehigher volume, Pao/m thereforeaveraged + 0.53 ± 0.05 cmH₂O/g, such that the coefficientof proportionality between the change in triangularis sterni lengthduring passive inflation and Pao/m was the same as that previously obtained for the parasternalintercostal and neck inspiratory muscles. These observations,therefore, confirm that there is a unique relationship between thefractional changes in length of the respiratory muscles, bothinspiratory and expiratory, during passive inflation and theirPao/m. Consequently, the maximal effect of a particular muscle on the lung can be predicted on the basisof its change in length during passive inflation and its mass. Ageometric analysis of the rib cage also established that thelengthening of the canine triangularis sterni during passive inflationis much greater than the shortening of the parasternal intercostalsbecause, in dogs, the costal cartilages slope downward from thesternum.

     

Paradoxical helium and sulfur hexafluoride single-breath washouts in short-term vs. sustained microgravity

Lauzon, Anne-Marie, G. Kim Prisk, Ann R. Elliott, SylviaVerbanck, Manuel Paiva, and John B. West. Paradoxical helium andsulfur hexafluoride single-breath washouts in short-term vs. sustainedmicrogravity. J. Appl. Physiol. 82(3):859-865, 1997.During single-breath washouts in normal gravity (1 G), the phase III slope of sulfur hexafluoride(SF₆) is steeper than that ofhelium (He). Two mechanisms can account for this:1) the higher diffusivity of Heenhances its homogeneous distribution; and2) the lower diffusivity ofSF₆ results in a more peripherallocation of the diffusion front, where airway asymmetry is larger.These mechanisms were thought to be gravity independent. However, weshowed during the Spacelab Life Sciences-2 spaceflight that insustained microgravity (µG) theSF₆-to-He slope difference isabolished. We repeated the protocol during short periods (27 s) of µG(parabolic flights). The subjects performed a vital-capacityinspiration and expiration of a gas containing 5% He-1.25%SF₆-balanceO₂. As in sustained µG, thephase III slopes of He and SF₆decreased. However, during short-term µG, theSF₆-to-He slope differenceincreased from 0.17 ± 0.03%/l in 1 G to 0.29 ± 0.06%/l inµG, respectively. This is contrary to sustained µG, in which theSF₆-to-He slope difference decreased from 0.25 ± 0.03%/l in 1 G to 0.01 ± 0.06%/lin µG. The increase in phase III slope difference in short-term µGwas caused by a larger decrease of He phase III slope compared with that in sustained µG. This suggests that changes in peripheral gasmixing seen in sustained µG are mainly due to alterations in thediffusive-convective inhomogeneity of He that require >27 s of µGto occur. Changes in pulmonary blood volume distribution or cardiogenicmixing may explain the differences between the results found inshort-term and sustained µG.

     

Respiratory system mechanics in sedated, paralyzed, morbidly obese patients

Pelosi, P., M. Croci, I. Ravagnan, M. Cerisara, P. Vicardi,A. Lissoni, and L. Gattinoni. Respiratory system mechanics insedated, paralyzed, morbidly obese patients J. Appl.Physiol. 82(3): 811-818, 1997.The effects ofinspiratory flow and inflation volume on the mechanical properties ofthe respiratory system in eight sedated and paralyzed postoperativemorbidly obese patients (aged 37.6 ± 11.8 yr who had never smokedand had normal preoperative seated spirometry) were investigated byusing the technique of rapid airway occlusion during constant-flowinflation. With the patients in the supine position, we measured theinterrupter resistance (Rint,rs), which in humans probably reflectsairway resistance, the "additional" resistance (Rrs) due toviscoelastic pressure dissipation and time-constant inequalities, andstatic respiratory elastance (Est,rs). Intra-abdominalpressure (IAP) was measured by using a bladder catheter, and functionalresidual capacity was measured by the helium-dilution technique. Theresults were compared with a previous study on 16 normal anesthetizedparalyzed humans. Compared with normal persons, we found that in obesesubjects: 1) functional residualcapacity was markedly lower (0.645 ± 0.208 liter) and IAP washigher (24 ± 2.2 cmH₂O);2) alveolar-arterial oxygenationgradient was increased (178 ± 59 mmHg);3) the volume-pressure curve of therespiratory system was curvilinear with an "inflection" point;4) Est,rs, Rint,rs, and Rrs werehigher than normal (29.3 ± 5.04 cmH₂O/l, 5.9 ± 2.4 cmH₂O ^· l^{1 ·} s,and 6.4 ± 1.6 cmH₂O ^· l^{1 ·} s,respectively); 5) Rint,rs increasedwith increasing inspiratory flow, Est,rs did not change, and Rrsdecreased progressively; and 6) withincreasing inflation volume, Rint,rs and Est,rs decreased, whereasRrs rose progressively. Overall, our data suggest that obesesubjects during sedation and paralysis are characterized by hypoxemiaand marked alterations of the mechanical properties of the respiratorysystem, largely explained by a reduction in lung volume due to theexcessive unopposed IAP.

     

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

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

     

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.

     

Multiple-breath washin of helium and sulfur hexafluoride in sustained microgravity

Prisk, G. Kim, Ann R. Elliott, Harold J. B. Guy, SylviaVerbanck, Manuel Paiva, and John B. West. Multiple-breath washin of helium and sulfur hexafluoride in sustained microgravity.J. Appl. Physiol. 84(1): 244-252, 1998.We performed multiple-breath washouts ofN₂ and simultaneous washins of Heand SF₆ with fixed tidal volume(~1,250 ml) and preinspiratory lung volume (approximately thesubject's functional residual capacity in the standing position) infour normal subjects (mean age 40 yr) standing and supine in normalgravity (1 G) and during exposure to sustained microgravity (µG). Theprimary objective was to examine the influence of diffusive processeson the residual, nongravitational ventilatory inhomogeneity in the lungin µG. We calculated several indexes of convective ventilatoryinhomogeneity from each gas species. A normal degree of ventilatoryinhomogeneity was seen in the standing position at 1 G that was largelyunaltered in the supine position. When we compared the standingposition in 1 G with µG, there were reductions in phase III slope inall gases, consistent with a reduction in convection-dependentinhomogeneity in the lung in µG, although considerable convectiveinhomogeneity persisted in µG. The reductions in the indexes ofconvection-dependent inhomogeneity were greater for He than forSF₆, suggesting that the distancesbetween remaining nonuniformly ventilated compartments in µG wereshort enough for diffusion of He to be an effective mechanism to reducegas concentration differences between them.

     

Curtailed respiration by repeated vs. isolated hypoxia in maturing piglets is unrelated to NTS ME or SP levels

Waters, Karen A., André Laferrière, JuliePaquette, Cynthia Goodyer, and Immanuela R. Moss. Curtailedrespiration by repeated vs. isolated hypoxia in maturing piglets isunrelated to NTS ME or SP levels. J. Appl.Physiol. 83(2): 522-529, 1997.In earlydevelopment, respiratory disorders can produce recurring hypoxicepisodes during sleep. To examine possible effects of daily repeatedvs. isolated hypoxic hypoxia, cardiorespiratory functions and central,respiratory-related neuromodulator levels in 21- to 32-day-old,chronically instrumented, unsedated piglets were compared between afifth sequential daily hypoxia and an isolated hypoxia (10%O₂-90%N₂ for 30 min). Diaphragmaticelectromyographic activity, heart rate and arterial pressure, and pHand gas tensions were measured. In vivo microdialysis, via chronicallyimplanted guides, served to sample interstitial substance P (SP) andmethionine-enkephalin (ME) at the level of the respiratory-relatednucleus tractus solitarii (NTS). Compared with an isolated hypoxia,repeated hypoxia resulted in 1)lower respiratory frequency (f), ventilation equivalent, and arterialpH, higher arterial PO₂during hypoxia, and lower f in recovery from hypoxia; and2) increased SP concentrations butno change in ME concentrations. We conclude that, in these maturingswine, repeated vs. isolated hypoxic exposure curtails respiratoryresponses to hypoxia by a mechanism(s) unrelated to SP or ME levels atthe NTS.

     

Control of the respiratory cycle in conscious humans

Rafferty, G. F., and W. N. Gardner. Control of therespiratory cycle in conscious humans. J. Appl.Physiol. 81(4): 1744-1753, 1996.We studied inconscious humans the relative strength of mechanisms controlling timingand drive components of the respiratory cycle around their resting setpoints. A system of auditory feedback with end-tidalPCO₂ held constant in mild hyperoxiavia an open circuit was used to induce subjects independently to change inspiratory time (TI) andtidal volume(VT_I)over a wide range above and below the resting values for every breathfor up to 1 h. Four protocols were studied in various levels ofhypercapnia (1-5% inspiredCO₂). We found thatTI (and expiratory time) could be changed over a wide range (1.17-2.86 s,P < 0.01 forTI) and VT_Iincreased by 500 ml (P < 0.01)without difficulty. However, in no protocol was it possible to decreaseVT_I belowthe free-breathing resting value in response to reduction of auditoryfeedback thresholds by up to 600 ml. This applied at all levels ofchemical drive studied, with restingVT_I valuesvarying from 1.06 to 1.74 liters. When reduction inVT_I wasforced by the more "programmed" procedure of isocapnic panting,end-expiratory volume was sacrificed to ensure that peak tidal volumereached a fixed absolute lung volume. These results suggest that theimperative for control of resting breathing is to prevent reduction ofVT_I belowthe level dictated by the prevailing chemical drive, presumably tosustain metabolic requirements of the body, whereas respiratory timingis weakly controlled consistent with the needs for speech and othernonmetabolic functions of breathing.

     

Mechanical advantage of sternomastoid and scalene muscles in dogs

Legrand, Alexandre, Vincent Ninane, and André DeTroyer. Mechanical advantage of sternomastoid and scalene muscles in dogs. J. Appl. Physiol. 82(5):1517-1522, 1997.Theoretical studies have led to the predictionthat the maximal effect of a given respiratory muscle on airway openingpressure (Pao) is the product of muscle mass, the maximal active muscletension per unit cross-sectional area, and the fractional change inmuscle length per unit volume increase of the relaxed chest wall. It has previously been shown that the parasternal intercostals behave inagreement with this prediction (A. De Troyer, A. Legrand, and T. A. Wilson. J. Physiol. (Lond.) 495:239-246, 1996; A. Legrand, T. A. Wilson, and A. DeTroyer. J. Appl. Physiol. 80:2097-2101, 1996). In the present study, we have tested theprediction further by measuring the response to passive inflation andthe pressure-generating ability of the sternomastoid and scalenemuscles in eight anesthetized dogs. With 1-liter passive inflation, thesternomastoids and scalenes shortened by 2.03 ± 0.17 and 5.98 ± 0.43%, respectively, of their relaxation length(P < 0.001). During maximalstimulation, the two muscles caused similar falls in Pao. However, thesternomastoids had greater mass such that the change in Pao (Pao)per unit muscle mass was 0.19 ± 0.02 cmH₂O/g for the scalenes and only0.07 ± 0.01 cmH₂O/g forthe sternomastoids (P < 0.001).After extension of the neck, there was a reduction in both the muscleshortening during passive inflation and the fall in Pao duringstimulation. The Pao per unit muscle mass was thus closely relatedto the change in length; the slope of the relationship was 3.1. These observations further support the concept that the fractional changes inlength of the respiratory muscles during passive inflation can be usedto predict their pressure-generating ability.

     

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.

     

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

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

     

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.

     

Zone of apposition in the passive diaphragm of the dog

Boriek, Aladin M., Joseph R. Rodarte, and Susan S. Margulies. Zone of apposition in the passive diaphragm of thedog. J. Appl. Physiol. 81(5): 1929-1940, 1996.Wedetermined the regional area of the diaphragmatic zone of apposition(ZAP) as well as the regional craniocaudal extent of the ZAP(ZAP_ht) of the passive diaphragm in six paralyzedanesthetized beagle dogs (8-12 kg) at residual lung volume (RV),functional residual capacity (FRC), FRC + 0.25 and FRC + 0.5 inspiratory capacity, and total lung capacity (TLC) in prone and supinepostures. To identify the caudal boundary of the ZAP, 17 lead markers(1 mm) were sutured to the abdominal side of the costal and cruraldiaphragms around the diaphragm insertion on the chest wall. Two weekslater, the dogs' caudal thoraces were scanned by the use of thedynamic spatial reconstructor (DSR), a prototype fast volumetric X-raycomputer tomographic scanner, developed at the Mayo Clinic. Thethree-dimensional spatial coordinates of the markers were identified(±1.4 mm), and the cranial boundary of the ZAP was determined from30-40 1.4-mm-thick sagittal and coronal slices in each DSR image.We interpolated the DSR data to find the position of the cranial andcaudal boundaries of the ZAP every 5° around the thorax and computedthe distribution of regional variation of area of the ZAP andZAP_ht as well as the total area of ZAP. TheZAP_ht and area of ZAP increased as lung volume decreasedand were largest near the lateral extremes of the rib cage. We measuredthe surface area of the rib cage cephaled to the ZAP(A_L) in both postures in another six beagle dogs(12-16 kg) of similar stature, scanned previously in the DSR. Weestimated the entire rib cage surface area(A_rc = A_ZAP +A_L). The A_ZAP as a percentageof A_rc increased more than threefold as lung volumedecreased from TLC to RV, from ~9 to 29% of A_rc.

     

A model of the spontaneously breathing patient: applications to intrinsic PEEP and work of breathing

Schuessler, Thomas F., Stewart B. Gottfried, and Jason H. T. Bates. A model of the spontaneously breathing patient: applications to intrinsic PEEP and work of breathing.J. Appl. Physiol. 82(5):1694-1703, 1997.Intrinsic positive end-expiratory pressure(PEEP_i) and inspiratory work ofbreathing (WI) are important factors in the management of severe obstructive respiratory disease. Weused a computer model of spontaneously breathing patients with chronicobstructive pulmonary disease to assess the sensitivity of measurementtechniques for dynamic PEEP_i(PEEP_{i dyn}) andWI to expiratory muscle activity(EMA) and cardiogenic oscillations (CGO) on esophageal pressure.Without EMA and CGO, bothPEEP_{i dyn} andWI were accurately estimated(r = 0.999 and 0.95, respectively). Addition of moderate EMA causedPEEP_{i dyn} andWI to be systematically overestimated by 141 and 52%, respectively. Furthermore, CGOintroduced large random errors, obliterating the correlation betweenthe true and estimated values for bothPEEP_{i dyn}(r = 0.29) andWI (r = 0.38). Thus the accurateestimation of PEEP_{i dyn} andWI requires steps to be taken toameliorate the adverse effects of both EMA and CGO. Taking advantage ofour simulations, we also investigated the relationship betweenPEEP_{i dyn} and staticPEEP_i(PEEP_{i stat}). ThePEEP_{i dyn}/PEEP_{i stat}ratio decreased as stress adaptation in the lung was increased,suggesting that heterogeneity of expiratory flow limitation isresponsible for the discrepancies betweenPEEP_{i dyn} andPEEP_{i stat} thathave been reported in patients with severe airwayobstruction.

     

Interaction of leg stiffness and surface stiffness during human hopping

Ferris, Daniel P., and Claire T. Farley. Interaction ofleg stiffness and surface stiffness during human hopping.J. Appl.Physiol. 82(1): 15-22, 1997.When mammals run,the overall musculoskeletal system behaves as a single linear "legspring." We used force platform and kinematic measurements todetermine whether leg spring stiffness(k_leg) isadjusted to accommodate changes in surface stiffness(k_surf) whenhumans hop in place, a good experimental model for examiningadjustments tok_leg in bouncinggaits. We found thatk_leg was greatlyincreased to accommodate surfaces of lower stiffnesses. The seriescombination ofk_leg andk_surf[total stiffness(k_tot)]was independent ofk_surf at a givenhopping frequency. For example, when humans hopped at a frequency of 2 Hz, they tripled theirk_leg on the leaststiff surface(k_surf = 26.1 kN/m; k_leg = 53.3 kN/m) compared with the most stiff surface(k_surf = 35,000 kN/m; k_leg = 17.8 kN/m). Values fork_tot were notsignificantly different on the least stiff surface (16.7 kN/m) and themost stiff surface (17.8 kN/m). Because of thek_leg adjustment,many aspects of the hopping mechanics (e.g., ground-contact time andcenter of mass vertical displacement) remained remarkably similardespite a >1,000-fold change ink_surf. This studyprovides insight into howk_leg adjustmentscan allow similar locomotion mechanics on the variety of terrainsencountered by runners in the natural world.

     

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.