Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method

Kim, Chong S., S. C. Hu, P. DeWitt, and T. R. Gerrity.Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method. J. Appl.Physiol. 81(5): 2203-2213, 1996.Detailedregional deposition of inhaled particles was investigated in youngadults (n = 11) by use of aserial bolus aerosol delivery technique. A small bolus (45 mlhalf-width) of monodisperse aerosols [1-, 3-, and5-µm particle diameter(D_p)] wasdelivered sequentially to a specific volumetric depth of the lung(100-500 ml in 50-ml increments), while the subject inhaled cleanair via a laser aerosol photometer (25-ml dead volume) with a constantflow rate ( = 150, 250, and 500 ml/s) andexhaled with the same without a pause to theresidual volume. Deposition efficiency (LDE) and deposition fraction in10 local volumetric regions and total deposition fraction of the lungwere obtained. LDE increased monotonically with increasing lung depthfor all three D_p.LDE was greater with smaller values in all lungregions. Deposition was distributed fairly evenly throughout the lungregions with a tendency for an enhancement in the distal lung regions for D_p = 1 µm.Deposition distribution was highly uneven forD_p = 3 and 5 µm, and the region of the peak deposition shifted toward the proximalregions with increasingD_p. Surface dosewas 1-5 times greater in the small airway regions and 2-17times greater in the large airway regions than in the alveolar regions.The results suggest that local or regional enhancement of deposition occurs in healthy subjects and that the local enhancement can be animportant factor in health risk assessment of inhaled particles.

     

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.

     

Effect of mechanical deformation on structure and function of polymorphonuclear leukocytes

Kitagawa, Yuko, Stephan F. Van Eeden, Darlene M. Redenbach,Maleki Daya, Blair A. M. Walker, Maria E. Klut, Barry R. Wiggs, andJames C. Hogg. Effect of mechanical deformation on structure andfunction of polymorphonuclear leukocytes. J. Appl.Physiol. 82(5): 1397-1405, 1997.The presentstudies were designed to test the hypothesis that mechanicaldeformation of polymorphonuclear leukocytes (PMN) leads to functionalchanges that might influence their transit in the pulmonarycapillaries. Human leukocytes were passed through 5- or 3-µm-porepolycarbonate filters under controlled conditions. Morphometricanalysis showed that the majority of PMN were deformed and that thisdeformation persisted longer after filtration through 3-µm filtersthan through 5-µm filters (P < 0.05) but did not result in the cytoskeletal polarizationcharacteristic of migrating cells. Flow cytometric studies of thefiltered PMN showed that there was a transient increase in thecytosolic free Ca²⁺ concentrationafter both 3- and 5-µm filtration (P < 0.01) with an increase in F-actin content after 3-µm filtration(P < 0.05). AlthoughL-selectin expression on PMN wasnot changed by either 5- or 3-µm filtration, CD18 and CD11b wereincreased by 3-µm filtration (P < 0.05). Priming of the PMN withN-formyl-methionyl-leucyl-phenylalanine (0.5 nM) before filtration resulted in an increase of CD11b by both 5 (P < 0.05)- and 3-µm(P < 0.01) filtration. Neither 5- nor 3-µm filtration induced hydrogen peroxide production. We conclude that mechanical deformation of PMN, similar to what occurs in thepulmonary microvessels, induces both structural and functional changesin the cells, which might influence their passage through the pulmonarycapillary bed.

     

Atrial distension in humans during microgravity induced by parabolic flights

Videbaek, Regitze, and Peter Norsk. Atrialdistension in humans during microgravity induced by parabolic flights.J. Appl. Physiol. 83(6):1862-1866, 1997.The hypothesis was tested that human cardiacfilling pressures increase and the left atrium is distended during 20-speriods of microgravity (µG) created by parabolic flights, comparedwith values of the 1-G supine position. Left atrial diameter(n = 8, echocardiography) increasedsignificantly during µG from 26.8 ± 1.2 to 30.4 ± 0.7 mm(P < 0.05). Simultaneously, centralvenous pressure (CVP; n = 6, transducer-tipped catheter) decreased from 5.8 ± 1.5 to 4.5 ± 1.1 mmHg (P < 0.05), and esophageal pressure (EP; n = 6) decreased from1.5 ± 1.6 to 4.1 ± 1.7 mmHg (P < 0.05). Thus transmural CVP(TCVP = CVP  EP; n = 4)increased during µG from 6.1 ± 3.2 to 10.4 ± 2.7 mmHg(P < 0.05). It is concluded thatshort periods of µG during parabolic flights induce an increase inTCVP and left atrial diameter in humans, compared with the resultsobtained in the 1-G horizontal supine position, despite a decrease inCVP.

     

Aerosol dispersion in human lung: comparison between numerical simulations and experiments for bolus tests

Darquenne, Chantal, Peter Brand, Joachim Heyder, and ManuelPaiva. Aerosol dispersion in human lung: comparison between numerical simulations and experiments for bolus tests.J. Appl. Physiol. 83(3): 966-974, 1997.Bolus inhalations of 0.87-µm-diameter particles wereadministered to 10 healthy subjects, and data were compared withnumerical simulations based on a one-dimensional model of aerosoltransport and deposition in the human lung (J. Appl.Physiol. 77: 2889-2898, 1994). Aerosol boluseswere inhaled at a constant flow rate into various volumetric lungdepths up to 1,500 ml. Parameters such as bolus half-width, mode shift, skewness, and deposition were used to characterize the bolus and todisplay convective mixing. The simulations described the experimental results reasonably well. The sensitivity of the simulations to different parameters was tested. Simulated half-width appeared to beinsensitive to altered values of the deposition term, whereas it wasgreatly affected by modified values of the apparent diffusion in thealveolar zone of the lung. Finally, further simulations were comparedin experiments with a fixed penetration volume and various flow rates.Comparison showed good agreement, which may be explained by the factthat half-width, mode shift, and skewness were little affected by theflow rate.

     

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.

     

High-resolution maps of regional ventilation utilizing inhaled fluorescent microspheres

Robertson, H. Thomas, Robb W. Glenny, Derek Stanford, LynnM. McInnes, Daniel L. Luchtel, and David Covert. High-resolution maps of regional ventilation utilizing inhaled fluorescentmicrospheres. J. Appl. Physiol. 82(3):943-953, 1997.The regional deposition of an inhaled aerosol of1.0-µm diameter fluorescent microspheres (FMS) was used to producehigh-resolution maps of regional ventilation. Five anesthetized, prone,mechanically ventilated pigs received two 10-min inhalations of pairsof different FMS labels, accompanied by intravenous injection of15.0-µm radioactive microspheres. The lungs were air dried and cutinto 1.9-cm³ pieces, with notationof the spatial coordinates for each piece. After measurement ofradioactive energy peaks, the tissue samples were soaked in2-ethoxyethyl acetate, and fluorescent emission peaks were recorded forthe wavelengths specific to each fluorescence label. The correlation offluorescence activity between simultaneously administered inhaled FMSranged from 0.98 to 0.99. The mean coefficient of variation forventilation for all 10 trials (47.9 ± 8.1%) was similar to thatfor perfusion (46.2 ± 6.3%). No physiologically significantgravitational gradient of ventilation or perfusion was present in theprone animals. The strongest predictor of the magnitude of regionalventilation among all animals was regional perfusion(r = 0.77 ± 0.13).

     

Anatomic distribution of pulmonary vascular compliance

Presson, Robert G., Jr., Said H. Audi, Christopher C. Hanger, Gerald M. Zenk, Richard A. Sidner, John H. Linehan, Wiltz W. Wagner, Jr., and Christopher A. Dawson. Anatomic distribution ofpulmonary vascular compliance. J. Appl.Physiol. 84(1): 303-310, 1998.Previously, thepressure changes after arterial and venous occlusion have been used tocharacterize the longitudinal distribution of pulmonary vascularresistance with respect to vascular compliance using compartmentalmodels. However, the compartments have not been defined anatomically.Using video microscopy of the subpleural microcirculation, we havemeasured the flow changes in ~40-µm arterioles and venules aftervenous, arterial, and double occlusion maneuvers. The quasi-steadyflows through these vessels after venous occlusion permitted anestimation of the compliance in three anatomic segments: arteries >40µm, veins >40 µm, and vessels <40 µm in diameter. We foundthat ~65% of the total pulmonary vascular compliance was in vessels<40 µm, presumably mostly capillaries. The transient portions ofthe pressure and flow data after venous, arterial, and double occlusionwere consistent with most of the arterial compliance being upstreamfrom most of the arterial resistance and most of the venous compliancebeing downstream from most of the venous resistance.

     

Interaction between ion transporters and the mucociliary transport system in dog and baboon

Winters, Scot L., and Donovan B. Yeates. Interactionbetween ion transporters and the mucociliary transport system in dogand baboon. J. Appl. Physiol. 83(4):1348-1359, 1997.To gain insight into the role of epithelial ionchannels, pumps, and cotransporters in regulating airway water andmucociliary transport, we administered inhibitors of theNa⁺ channel (amiloride),3Na-2K-adenosinetriphosphatase (acetylstrophanthidin), and Na-K-2Clcotransporter (furosemide) to anesthetized dogs and/or baboons.Tracheal ciliary beat frequency was measured by using heterodyne laserlight scattering. Tracheal mucus velocity (TMV) and bronchialmucociliary clearance (BMC) or lung mucociliary clearance were measuredby using radioaerosols and nuclear imaging. Respiratory tract fluidoutput was collected by using a secretion-collecting endotracheal tube.In six dogs, amiloride aerosol [lung deposition, 96 ± 11 µg(means ± SE)] had minimal effect, whereasacetylstrophanthidin aerosol (lung deposition, 71 ± 9 µg)increased BMC, and furosemide (40 mg iv) markedly increased TMV. Infive baboons, TMV increased after iv furosemide administration (2 mg/kg) as well as by aerosol (lung deposition, 20 ± 3 mg), coincident with increases in ciliary-mucus coupling from 11.5 ± 0.1 to 29.5 ± 0.4 and 46.5 ± 0.7 µm/beat, respectively.Furosemide also increased lung mucociliary clearance in baboons. Indogs, respiratory tract fluid output increased after intravenousfurosemide from 2.2 ± 0.5 to 6.8 ± 1.7 mg/min. When combinedwith dry-air inhalation, furosemide failed to stimulate TMV andreversed the inhibition of BMC by dry air. Thus pharmacological manipulation of the Na-K-2Cl cotransporter and the3Na-2K-adenosinetriphosphatase pump may provide increases of clinicalrelevance in airway hydration and mucociliary transport.

     

Regional deposition of inhaled particles in human lungs: comparison between men and women

We measured detailed regional depositionpatterns of inhaled particles in healthy adult male(n = 11; 25 ± 4 yr of age) and female (n = 11; 25 ± 3 yr of age)subjects by means of a serial bolus aerosol delivery technique formonodisperse fine [particle diameter(D_p) = 1 µm] and coarse aerosols(D_p = 3 and 5 µm). The bolus aerosol (40 ml half-width) was delivered to a specificvolumetric depth (Vp) of the lung ranging from 100 to 500 ml with a50-ml increment, and local deposition fraction (LDF) was assessed for each of the 10 local volumetric regions. In all subjects, the deposition distribution pattern was very uneven with respect to Vp,showing characteristic unimodal curves with respect to particle sizeand flow rate. However, the unevenness was more pronounced in women.LDF tended to be greater in all regions of the lung in women than inmen for D_p = 1 µm. For D_p = 3 and 5 µm, LDF showed a marked enhancement in the shallow region of Vp  200 ml in women compared with men(P < 0.05). LDF in women wascomparable to or smaller than those of men in deep lung regions of Vp > 200 ml. Total lung deposition was comparable between men and womenfor fine particles but was consistently greater in women than men forcoarse particles regardless of flow rates used: the difference rangedfrom 9 to 31% and was greater with higher flow rates(P < 0.05). The results indicatethat 1) particledeposition characteristics differ between healthy men and women undercontrolled breathing conditions and2) deposition in women is greaterthan that in men.

     

Cardiogenic oscillation phase relationships during single-breath tests performed in microgravity

Lauzon, Anne-Marie, Ann R. Elliott, Manuel Paiva, John B. West, and G. Kim Prisk. Cardiogenic oscillation phaserelationships during single-breath tests performed inmicrogravity. J. Appl. Physiol. 84(2):661-668, 1998.We studied the phase relationships of thecardiogenic oscillations in the phase III portion of single-breath washouts (SBW) in normal gravity (1 G) and in sustained microgravity (µG). The SBW consisted of a vital capacity inspiration of 5% He-1.25% sulfurhexafluoride-balanceO₂, preceded at residual volume bya 150-ml Ar bolus. Pairs of gas signals, all of which still showedcardiogenic oscillations, were cross-correlated, and their phasedifference was expressed as an angle. Phase relationships betweeninspired gases (e.g., He) and resident gas(N₂) showed no change from 1 G(211 ± 9°) to µG (163 ± 7°). Ar bolus and He wereunaltered between 1 G (173 ± 15°) and µG (211 ± 25°),showing that airway closure in µG remains in regions of high specific ventilation and suggesting that airway closure results from lung regions reaching low regional volume near residual volume. In contrast,CO₂ reversed phase with He between1 G (332 ± 6°) and µG (263 ± 27°), stronglysuggesting that, in µG, areas of high ventilation are associated withhigh ventilation-perfusion ratio (A/).This widening of the range ofA/in µG may explain previous measurements (G. K. Prisk, A. R. Elliott,H. J. B. Guy, J. M. Kosonen, and J. B. West. J. Appl.Physiol. 79: 1290-1298, 1995) of an overallunaltered range ofA/in µG, despite more homogeneous distributions of both ventilation andperfusion.

     

Efficacy of forced-air and inhalation rewarming by using a human model for severe hypothermia

Goheen, M. S. L., M. B. Ducharme, G. P. Kenny, C. E. Johnston, John Frim, Gerald K. Bristow, and Gordon G. Giesbrecht. Efficacy of forced-air and inhalation rewarming by using a humanmodel for severe hypothermia. J. Appl.Physiol. 83(5): 1635-1640, 1997.We recentlydeveloped a nonshivering human model for severe hypothermia by usingmeperidine to inhibit shivering in mildly hypothermic subjects. Thisthermal model was used to evaluate warming techniques. On threeoccasions, eight subjects were immersed for ~25 min in 9°C water.Meperidine (1.5 mg/kg) was injected before the subjects exited thewater. Subjects were then removed, insulated, and rewarmed in anambient temperature of 20°C with either1) spontaneous rewarming (control),2) inhalation rewarming withsaturated air at ~43°C, or 3)forced-air warming. Additional meperidine (to a maximumcumulative dose of 2.5 mg/kg) was given to maintain shiveringinhibition. The core temperature afterdrop was 30-40% less duringforced-air warming (0.9°C) than during control (1.4°C) andinhalation rewarming (1.2°C) (P < 0.05). Rewarming rate was 6- to 10-fold greater during forced-airwarming (2.40°C/h) than during control (0.41°C/h) andinhalation rewarming (0.23°C/h) (P < 0.05). In nonshivering hypothermic subjects, forced-air warming provided a rewarming advantage, but inhalation rewarming did not.

     

Regional deposition and retention of particles in shallow, inhaled boluses: effect of lung volume

The regionaldeposition of particles in boluses delivered to shallow lung depths andtheir subsequent retention in the airways may depend on the lung volumeat which the boluses are delivered. To evaluate the effectof end-inspiratory lung volume on aerosol bolus delivery, we hadhealthy subjects inhale radiolabeled, monodisperse aerosol(^99mTc-iron oxide, 3.5-µm massmedian aerodynamic diameter) boluses (40 ml) to a volumetric frontdepth of 70 ml into the lung at lung volumes of 50, 70, and 85% oftotal lung capacity (TLC) end inhalation. By gamma camera analysis, wefound significantly greater deposition in the left (L) vs. right (R)lungs at the 70 and 85% TLC end inhalation; ratio of deposition in Lto R lung, normalized to L-to-R ratio of lung volume (mean L/R), was1.60 ± 0.45 (SD) and 1.96 ± 0.72, respectively(P < 0.001 for comparison to 1.0) for posterior images. However, at 50% TLC, L/R was 1.23 ± 0.37, not significantly different from 1.0. These data suggest that the L andR lungs may be expanding nonuniformly at higher lung volumes. On theother hand, subsequent retention of deposited particles at 2 and 24 hpostdeposition was independent of L/R at the various lung volumes. Thusasymmetric bolus ventilation for these very shallow boluses does notlead to significant increases in peripheral alveolar deposition. Thesedata may prove useful for 1)designing aerosol delivery techniques to target bronchial airways and2) understanding airway retention ofinhaled particles.

     

Methacholine-induced bronchoconstriction in rats: effects of intravenous vs. aerosol delivery

Peták, Ferenc, Zoltán Hantos, ÁgnesAdamicza, Tibor Asztalos, and Peter D. Sly. Methacholine-inducedbronchoconstriction in rats: effects of intravenous vs. aerosoldelivery. J. Appl. Physiol. 82(5):1479-1487, 1997.To determine the predominant site of action ofmethacholine (MCh) on lung mechanics, two groups of open-chestSprague-Dawley rats were studied. Five rats were measured duringintravenous infusion of MCh (iv group), with doubling of concentrationsfrom 1 to 16 µg · kg¹ · min¹.Seven rats were measured after aerosol administration of MCh with dosesdoubled from 1 to 16 mg/ml (ae group). Pulmonary input impedance(ZL) between 0.5 and 21 Hz wasdetermined by using a wave-tube technique. A model containing airwayresistance (Raw) and inertance (Iaw) and parenchymal damping (G) andelastance (H) was fitted to theZL spectra. In the iv group, MChinduced dose-dependent increases in Raw [peak response 270 ± 9 (SE) % of the control level; P < 0.05] and in G (340 ± 150%;P < 0.05), with no increase inIaw (30 ± 59%) orH (111 ± 9%). In the ae group, thedose-dependent increases in Raw (191 ± 14%;P < 0.05) andG (385 ± 35%; P < 0.05) were associated with a significant increase in H (202 ± 8%; P < 0.05).Measurements with different resident gases [air vs. neon-oxygenmixture, as suggested (K. R. Lutchen, Z. Hantos, F. Peták,Á. Adamicza, and B. Suki. J. Appl.Physiol. 80: 1841-1849, 1996)] in thecontrol and constricted states in another group of rats suggested thatthe entire increase seen in G during the ivchallenge was due to ventilation inhomogeneity, whereas the aechallenge might also have involved real tissue contractions viaselective stimulation of the muscarinic receptors.

     

Innervation pattern of guinea pig pulmonary vasculature depends on vascular diameter

Haberberger, Rainer, Michael Schemann, Holger Sann, andWolfgang Kummer. Innervation pattern of guinea pig pulmonary vasculature depends on vascular diameter. J. Appl.Physiol. 82(2): 426-434, 1997.The pulmonaryvasculature is supplied by various neurochemically distinct types ofnerve fibers, including sensory substance P-containing and autonomicnoradrenergic, nitrergic, and cholinergic axons.Pharmacological experiments have suggested that various segments of thepulmonary vascular tree respond differently to the respectiveneuromediators. We, therefore, aimed to determine histochemically andimmunohistochemically for each of these neurochemically distinctperivascular axons their quantitative distribution along the vasculartree from the extrapulmonary trunks to the smallest intraparenchymalramifications in control guinea pigs(n = 5). Generally, arterialinnervation was more developed than that of veins. Along the arterialtree, noradrenergic and substance P-containing axons were ubiquitousfrom the pulmonary trunk to smallest intraparenchymal vessels, whereasnitrergic axons were practically restricted to large (>700-µm)extrapulmonary arteries. Cholinergic axons were regularly present atarteries down to 100 µm in diameter and innervated two-thirds ofsmall arteries (50-100 µm). The results demonstrate thatthe noradrenergic vasoconstrictor innervation extends throughout thepulmonary vascular system whereas the innervation pattern with varioustypes of vasodilator fibers changes with vascular diameter, parallel toknown pharmacological differences in cholinergic and nitrergicvasodilator effects.

     

Effect of glucose supplement timing on protein metabolism after resistance training

Roy, B. D., M. A. Tarnopolsky, J. D. MacDougall, J. Fowles,and K. E. Yarasheski. Effect of glucose supplement timing onprotein metabolism after resistance training. J. Appl.Physiol. 82(6): 1882-1888, 1997.We determinedthe effect of the timing of glucose supplementation on fractionalmuscle protein synthetic rate (FSR), urinary urea excretion, and wholebody and myofibrillar protein degradation after resistance exercise.Eight healthy men performed unilateral knee extensor exercise (8 sets/~10 repetitions/~85% of 1 single maximal repetition). Theyreceived a carbohydrate (CHO) supplement (1 g/kg) or placebo (Pl)immediately (t = 0 h) and 1 h(t = +1 h) postexercise. FSR wasdetermined for exercised (Ex) and control (Con) limbs by incrementalL-[1-¹³C]leucineenrichment into the vastus lateralis over ~10 h postexercise. Insulinwas greater (P < 0.01) at 0.5, 0.75, 1.25, 1.5, 1.75, and 2 h, and glucose was greater(P < 0.05) at 0.5 and 0.75 h for CHO compared with Pl condition. FSR was 36.1% greater in the CHO/Ex leg than in the CHO/Con leg(P = not significant) and6.3% greater in the Pl/Ex leg than in the Pl/Con leg(P = not significant). 3-Methylhistidine excretion was lower in the CHO (110.43 ± 3.62 µmol/g creatinine) than Pl condition (120.14 ± 5.82, P < 0.05) as was urinary ureanitrogen (8.60 ± 0.66 vs. 12.28 ± 1.84 g/g creatinine,P < 0.05). This suggests that CHOsupplementation (1 g/kg) immediately and 1 h after resistance exercisecan decrease myofibrillar protein breakdown and urinary urea excretion,resulting in a more positive body protein balance.

     

Exercise performance, red blood cell deformability, and lipid peroxidation: effects of fish oil and vitamin E

Oostenbrug, G. S., R. P. Mensink, M. R. Hardeman, T. DeVries, F. Brouns, and G. Hornstra. Exercise performance, red bloodcell deformability, and lipid peroxidation: effects of fish oil andvitamin E. J. Appl. Physiol. 83(3):746-752, 1997.Previous studies have indicated that fish oilsupplementation increases red blood cell (RBC) deformability, which mayimprove exercise performance. Exercise alone, or in combination with anincrease in fatty acid unsaturation, however, may enhance lipidperoxidation. Effects of a bicycle time trial of ~1 h on RBCcharacteristics and lipid peroxidation were, therefore, studied in 24 trained cyclists. After 3 wk of fish oil supplementation (6 g/day),without or with vitamin E (300 IU/day), trial performance,RBC characteristics, and lipid peroxidation were measuredagain. RBC deformability appeared to decrease duringendurance exercise. After correction for hemoconcentration, plasmatotal tocopherol concentrations decreased by 0.77 µmol/l(P = 0.012) or 2.9% and carotenoidconcentrations by 0.08 µmol/l (P = 0.0008) or 4.5%. Endurance exercise did not affect the lag time andrate of in vitro oxidation of low-density lipoproteins (LDLs), but themaximum amount of conjugated dienes formed decreased by 2.1 ± 1.0 µmol/mmol LDL cholesterol (P = 0.042) or 1.2%. Fish oil supplementation with andwithout vitamin E did not affect RBC characteristics or exerciseperformance. Both supplements decreased the rate of LDL oxidation, andfish oil supplementation with vitamin E delayed oxidation. The amountof dienes, however, was not affected. The supplements also did notchange effects of exercise. We conclude that the changes observedduring endurance exercise may indicate increased oxidative stress, butfurther research is necessary to confirm this. Fish oil supplementation does not improve endurance performance, but it also does not cause oraugment changes in antioxidant levels or LDL oxidation during exercise.

     

Estimation of thickness of airwaysurface liquid in ferret trachea in vitro

Duneclift, S., U. Wells, and J. Widdicombe. Estimationof thickness of airway surface liquid in ferret trachea in vitro. J. Appl. Physiol. 83(3): 761-767, 1997.The tracheae of ferrets and rabbits were mounted in vitro inorgan baths. While the tracheae were liquid filled, the permeabilitycoefficient ( P) was determined, and then while thetracheae were air filled, the percent clearance for^99mTc-labeleddiethylenetriaminepentaacetic acid (DTPA) was determined. The thicknessof airway surface liquid (ASL) was estimated by three methods.1) The initial concentration of^99mTc-DTPA and the total amount of^99mTc-DTPA (the sum of thatentering the outside medium, that draining from the trachea, and thatwashed out at the end of 40 min) gave the initial volume of ASL andthus its thickness. Mean values were 45.7 µm for the ferret and 41.9 µm for the rabbit. 2) Estimates ofASL thickness at the end of the 40-min period, based on the final^99mTc-DTPA concentration and theamount in the washout, were 42.9 µm for ferret and 45.4 µm forrabbit. 3) The ratio of Pto percent clearance gave mean ASL thickness values of 49.2 µm forthe ferret and 40.3 µm for the rabbit. Thus three separate methodsfor determining ASL thickness give very similar results, with means inthe range 40-49 µm. Administration of methacholine or atropineto ferret tracheae did not significantly change ASL thickness.

     

Importance of airway blood flow on particle clearance from the lung

Wagner, Elizabeth M., and W. Michael Foster. Importanceof airway blood flow on particle clearance from the lung.J. Appl. Physiol. 81(5):1878-1883, 1996.The role of the airway circulation insupporting mucociliary function has been essentially unstudied. Weevaluated the airway clearance of inert, insoluble particles inanesthetized ventilated sheep (n = 8),in which bronchial perfusion was controlled, to determine whetherairway mucosal blood flow is essential for maintaining surfacetransport of particles through airways. The bronchial branch of thebronchoesophageal artery was cannulated and perfused with autologousblood at control flow (0.6 ml ^· min^{1 ·} kg¹)or perfusion was stopped. With the sheep in a supine position and aftera steady-state ¹³³Xe ventilationscan for designation of lung zones of interest, an inert^99mTc-labeled sulfur colloidaerosol (2.1-µm diameter) was deposited in the lung. The clearancekinetics of the radiolabeled particles were determined from theactivity-time data obtained for right and left lung zones. At 60 minpostdeposition of aerosol, average airway particle retention forcontrol bronchial blood flow conditions was 57 ± 7 (SE)% for theright and 53 ± 8% for the left lung zones. Clearance of particleswas significantly impaired when bronchial blood flow was stopped, e.g.,right and left lung zones averaged 77 ± 6 and 76 ± 7% at 60 min, respectively (P < 0.05). Thesedata demonstrate a significant influence of the bronchial circulation on mucociliary transport of insoluble particles. Potential mechanisms that may account for these results include the importance of the bronchial circulation for nutrient flow, maintenance of airway walltemperature and humidity, and release of mediators and sequelae associated with tissue ischemia.

     

Instantaneous force-velocity-length relationship in diaphragmatic sarcomere

Coirault, Catherine, Denis Chemla, Jean-Claude Pourny,Francine Lambert, and Yves Lecarpentier. Instantaneousforce-velocity-length relationship in diaphragmatic sarcomere.J. Appl. Physiol. 82(2): 404-412, 1997.The simultaneous analysis of muscle force, length, velocity, andtime has been shown to precisely characterize the mechanicalperformance of isolated striated muscle. We tested the hypothesis thatthe three-dimensional force-velocity-length relationship reflectsmechanical properties of sarcomeres. In hamster diaphragm strips,instantaneous sarcomere length (SL) and muscle length were simultaneously measured during afterloaded twitches. SL was measured by means of laser diffraction. Wealso studied the influence of initialSL, abrupt changes in total load, and2 × 10⁷ M dantrolene.Baseline resting SL at the apex of thelength-active tension curve was 2.2 ± 0.1 µm, whereasSL at peak shortening was 1.6 ± 0.1 µm in the preloaded twitch and 2.1 ± 0.1 µm in the "isometric" twitch. Over the whole load continuum and at anygiven level of isotonic load, there was a unique relationship between instantaneous sarcomere velocity and instantaneousSL. Part of this relationship was timeindependent and initial SL independent and was markedly downshifted after dantrolene. When five different muscle regions were considered, there were no significant variations ofSL and sarcomere kinetics along themuscle. These results indicate that the time- and initiallength-independent part of the instantaneous force-velocity-lengthrelationship previously described in muscle strips reflects intrinsicsarcomere mechanical properties.