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.

     

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.

     

Pulmonary blood flow distribution has a hilar-to-peripheral gradient in awake, prone sheep

Walther, Sten M., Karen B. Domino, Robb W. Glenny, Nayak L. Polissar, and Michael P. Hlastala. Pulmonary blood flow distribution has a hilar-to-peripheral gradient in awake, prone sheep.J. Appl. Physiol. 82(2): 678-685, 1997.We examined the pulmonary blood flow distribution withintravenous fluorescent microspheres (15 µm) in nine prone,unanesthetized, lambs. Lungs flushed free of blood were air-dried attotal lung capacity and sectioned into~2-cm³ pieces. The pieces wereweighed, identified by lobe, and assigned spatial coordinates.Fluorescence was read on a spectrophotometer, and signals werecorrected for piece weight and normalized to mean flow. Pulmonary bloodflow heterogeneity was assessed by using the coefficient of variationof the flow data. The number of pieces (±SD) analyzed were 1,249 ± 150/animal. Heterogeneity of blood flow was 29.5 ± 6.5%(coefficient of variation = SD/mean). Pulmonary blood flow decreasedwith distance from hilus (P < 0.002) but did not change significantly with vertical height. Distance fromthe hilus was the best predictor of pulmonary blood flow (R² = 0.201) and,together with spatial coordinates and lobe, accounted for 33.7 ± 12.0% of blood flow variability. We conclude that pulmonary blood flowin the awake, prone sheep is distributed with a hilar-to-peripheral gradient but no significant vertical gradient.

     

Spatial pattern of pulmonary blood flow distribution is stable over days

Glenny, Robb W., Steven McKinney, and H. Thomas Robertson.Spatial pattern of pulmonary blood flow distribution is stableover days. J. Appl. Physiol. 82(3):902-907, 1997.Despite the heterogeneous distribution of regionalpulmonary perfusion over space, local perfusion remains stable overshort time periods (20-100 min). The purpose ofthis study was to determine whether the spatial distribution ofpulmonary perfusion remains stable over longer time periods (1-5days). Regional blood flow was measured each day for 5 days in five awake standing dogs. Fluorescent microspheres of differentcolors were injected into a limb vein over 30 s on each day. After thelast microsphere injection, the dogs were killed, and lungs wereflushed free of blood, excised, dried at total lung capacity, and dicedinto ~2-cm³ pieces(n = 1,296-1,487 per dog).Relative blood flow to each piece on each day was determined byextracting the fluorescent dyes and determining the concentrations ofeach color. We established that blood flow is spatiallyheterogeneous with a coefficient of variation of 29.5 ± 2%. Blood flow to each piece is highly correlated with flow to thesame piece on all days (r = 0.930 ± 0.006). The temporal heterogeneity of regional perfusion as measured by the coefficient of variation is 6.9 ± 0.7% over the 5 days and is nonrandom. The magnitude of spatial and temporal variationis significantly less than previously reported in a study in whichanesthetized and mechanically ventilated dogs were used. We concludethat spatial distribution of pulmonary blood flowremains stable over days and we speculate that in the normal awake dogregional perfusion is determined primarily by a fixed structure such asthe geometry of the pulmonary vascular tree rather than by localvasoactive regulators. Anesthesia and/or mechanical ventilationmay increase the temporal variability in regionalperfusion.

     

Pulmonary embolization causes hypoxemia by redistributing regional blood flow without changing ventilation

To explore mechanisms of hypoxemia after acutepulmonary embolism, we measured regional pulmonary blood flow andalveolar ventilation before and after embolization with 780-µm beadsin five anesthetized, mechanically ventilated pigs. Regionalventilation and perfusion were determined in~2.0-cm³ lung volumes by using1-µm-diameter aerosolized and 15-µm-diameter injected fluorescentmicrospheres. Hypoxemia after embolization resulted from increasedperfusion to regions with low ventilation-to-perfusion ratios.Embolization caused an increase in perfusion heterogeneity and a fallin the correlation between ventilation and perfusion. Correlationbetween regional ventilation pre- and postembolization was greater thancorrelation between regional perfusion pre- and postembolization. Themajority of regional ventilation-to-perfusion ratio heterogeneity wasattributable to changes in regional perfusion. Regional perfusionredistribution without compensatory changes in regional ventilation isresponsible for hypoxemia after pulmonary vascular embolization in pigs.

     

Absorption from different intestinal segments during exercise

Lambert, G. P., R. T. Chang, T. Xia, R. W. Summers, and C. V. Gisolfi. Absorption from different intestinal segments duringexercise. J. Appl. Physiol. 83(1):204-212, 1997.This study evaluated intestinal absorption fromthe first 75 cm of the proximal small intestine during 85 min of cycleexercise [63.6 ± 0.7% peakO₂ consumption(O_{2 peak})]while subjects ingested either an isotonic carbohydrate-electrolytebeverage (CHO-E) or a water placebo (WP). The CHO-E beverage contained117 mM (4%) sucrose, 111 mM (2%) glucose, 18 meqNa⁺, and 3 meqK⁺. The two experiments wereperformed a week apart by seven subjects (6 men and 1 woman; meanO_{2 peak} = 53.5 ± 6.5 ml · kg¹ · min¹).Nasogastric and multilumen tubes were fluoroscopically positioned inthe gastric antrum and duodenojejunum, respectively. Subjects ingested23 ml/kg body weight of the test solution, 20% (383 ± 11 ml) ofthis volume 5 min before exercise and 10% (191 ± 5 ml) every 10 min thereafter. By using the rate of gastric emptying (18.1 ± 1.1 vs. 19.2 ± 0.7 ml/min for WP and CHO-E, respectively) as the rateof intestinal perfusion, intestinal absorption was determined bysegmental perfusion from the duodenum (0-25 cm) and jejunum(25-50 and 50-75 cm). Water flux was different(P < 0.05) between solutions in the0- to 25- and 25- to 50-cm segments for WP vs. CHO-E (30.7 ± 2.7 vs. 15.0 ± 2.9 and 3.8 ± 1.1 vs. 11.9 ± 3.3 ml · cm¹ · h¹,respectively). Furthermore, water flux differed(P < 0.05) for WP in a comparison ofthe 0- to 25- to the 25- to 50-cm segment. Total solute flux (TSF) wasnot significantly different among segments for a given solution orbetween solutions for a given segment. There was no difference betweentrials for percent change in plasma volume. These results indicate that1) fluid absorption in the proximalsmall intestine depends on the segment studied and2) solution composition cansignificantly effect water absorption rate in differentintestinal segments.

     

Suppressive action of endogenous adenosine on ovine fetal nonshivering thermogenesis

Ball, Karen T., Tania R. Gunn, Peter D. Gluckman, and GordonG. Power. Suppressive action of endogenous adenosine on ovinefetal nonshivering thermogenesis. J. Appl.Physiol. 81(6): 2393-2398, 1996.Nonshiveringthermogenesis is not initiated when the fetal sheep is cooled in uterobut appears to require the removal of an inhibitor of placental originat birth. To test whether adenosine is such an inhibitor, we examinedthe effect of the adenosine antagonist theophylline on the initiationof nonshivering thermogenesis during sequential cooling, ventilation, and umbilical cord occlusion in utero. Theophylline (18 mg/kg bolus and0.6 mg ^· kg^{1 ·} min¹thereafter) was infused for 90 min before and 90 min after cord occlusion. Theophylline enhanced the nonshivering thermogenic freefatty acid (FFA) and glycerol responses before cord occlusion, raisingFFA concentrations 99% to 415 ± 60 µeq/l(P < 0.01) and glycerol levels 87%to 526 ± 135 µmol/l (P < 0.05). These FFA (P < 0.001) andglycerol (P < 0.05) concentrationswere significantly greater than the corresponding period during thebirth-simulation control. Umbilical cord occlusion did not alter FFAlevels but induced a 41% rise in glycerol concentrations to 774 ± 203 µmol/l (P < 0.05). Theincreases in nonshivering thermogenic indexes after the administrationof the adenosine-receptor antagonist suggest that the quiescent stateof ovine fetal brown adipose tissue may result, in part, from the tonicinhibitory actions of adenosine and that a decrease in adenosineconcentrations enhances nonshivering thermogenesis. However, thefurther rise after umbilical cord occlusion suggests that at least oneother inhibitor of placental origin inhibits nonshivering thermogenesisbefore birth.

     

Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion

Simon, Brett A., Koichi Tsuzaki, and Jose G. Venegas.Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion. J. Appl.Physiol. 82(3): 882-891, 1997.Regionalpneumoconstriction induced by alveolar hypocapnia is an importanthomeostatic mechanism for optimization of ventilation-perfusionmatching. We used positron imaging of ¹³NN-equilibrated lungs to measurethe distribution of regional tidal volume(VT), lung volume(VL), and lung impedance(Z) before and after left (L)pulmonary artery occlusion (PAO) in eight anesthetized, open-chestdogs. Measurements were made during eucapnic sinusoidal ventilation at0.2 Hz with 4-cmH₂O positive end expiratory pressure. Right(R) and L lung impedances(ZRandZL)were determined from carinal pressure and positron imaging of dynamicregional VL. LPAO caused anincrease in|ZL|relative to|ZR|,resulting in a shift in VT awayfrom the PAO side, with a L/R|Z| ratio changing from 1.20 ± 0.07 (mean ± SE) to 2.79 ± 0.85 after LPAO(P < 0.05). Although mean L lungVL decreased slightly, theVL normalized parametersspecific admittance and specific compliance both significantly decreased with PAO. Lung recoil pressure at 50% totallung capacity also increased after PAO. We conclude that PAO results inan increase in regional lung Z thatshifts ventilation away from the affected area at normal breathingfrequencies and that this effect is not due to a change inVL but reflects mechanicalconstriction at the tissue level.

     

Effect of pulmonary emphysema on diaphragm capillary geometry

Poole, David C., and Odile Mathieu-Costello. Effect ofpulmonary emphysema on diaphragm capillary geometry.J. Appl. Physiol. 82(2): 599-606, 1997.In emphysema, the diaphragm shortens by losing sarcomeres. Wehypothesized that unless capillaries undergo a similar shortening,capillary geometry must be altered. Without quantifying this geometry,capillary length and surface area per fiber volume, which are criticalmeasurements of the structural potential for blood-tissue exchange,cannot be resolved. Five months after intratracheal elastase (E) orsaline (control; C) instillation, diaphragms from male Syrian goldenhamsters were glutaraldehyde perfusion fixed in situ at reference lungpositions (residual volume, functional residual capacity, total lungcapacity) to provide diaphragms fixed over a range of sarcomerelengths. Subsequently, diaphragms were processed for electronmicroscopy and analyzed morphometrically. Emphysema increased lungvolume changes from 20 to 25 cmH₂O airway pressure (i.e.,passive vital capacity) and excised lung volume (bothP < 0.001). In each region of thecostal diaphragm (i.e., ventral, medial, dorsal), sarcomere number wasreduced (all P < 0.05).Capillary-to-fiber ratio increased (C = 2.2 ± 0.1, E = 2.8 ± 0.1; P < 0.01) and fibershypertrophied (C = 815 ± 35, E = 987 ± 67 µm²;P < 0.05; both values at 2.5 µmsarcomere length). Capillary geometry was markedly altered by the lossof sarcomeres in series. Specifically, the additional capillary lengthderived from capillary tortuosity and branching was increased by 183%at 2.5 µm sarcomere length compared with C values (C, 359 ± 43;E, 1,020 ± 158 mm²,P < 0.01). This significantlyincreased total capillary length (C, 3,115 ± 173; E, 3,851 ± 219 mm² at 2.5 µm,P < 0.05) and surface area (C, 456 ± 13; E, 519 ± 24 cm¹,P < 0.05) per fiber volume. Thusemphysema substantially alters diaphragm capillary geometry andaugments the capillary length and surface area available forblood-tissue exchange.

     

Development of ventilatory responsiveness to progressive hypoxia and hypercapnia in low-birth-weight lambs

Moss, T. J., M. G. Davey, G. J. McCrabb, and R. Harding.Development of ventilatory responsiveness to progressive hypoxia and hypercapnia in low-birth-weight lambs. J. Appl.Physiol. 81(4): 1555-1561, 1996.Our aim was todetermine the effects of low birth weight on ventilatory responses toprogressive hypoxia and hypercapnia during early postnatal life. Sevenlow-birth-weight (2.7 ± 0.3 kg) and five normal-birth-weight (4.8 ± 0.2 kg) lambs, all born at term, underwent weekly rebreathingtests during wakefulness while arterialPO₂,PCO₂, and pH were measured. Hypoxicventilatory responsiveness (HOVR; percent increase in ventilation whenarterial PO₂ fell to 60% of resting values) increased in normal lambs from 86.6 ± 7.1% atweek 1 to 227.4 ± 24.9% atweek 6. In low-birth-weight lambs,HOVR was not significantly different at week1 (60.1 ± 18.7%) from that of normal lambs but didnot increase with postnatal age (56.6 ± 19.3% atweek 6). HOVR of all lambs at 6 wkwas significantly correlated with birth weight(r² = 0.8).Hypercapnic ventilatory responsiveness (gradient of ventilation vs.arterial PCO₂) did not change withage and was not significantly different between groups [84.7 ± 7.5 (low-birth-weight lambs) vs. 89.4 ± 6.6 ml ^· min^{1 ·} kg^{1 ·} mmHg¹(normal lambs)]. We conclude that intrauterine conditions that impair fetal growth lead to the failure of HOVR to increase with age.

     

Intercellular Transport and Cytoplasmic Streaming in Chara hispida

The correlation between the velocities of cytoplasmic streamingand of translocation of ¹⁴C-photosynthate and ³²P-phosphateassociated radioactivity has been investigated in whole plantsof the green freshwater alga Chara hispida L. Tracer was suppliedto the plant's rhizoid system in a split-chamber. The velocityof cytoplasmic streaming of 52±3.3 µm s^–1compares with 57±10 µm s^–1 found for ¹⁴C-transportand 32±20 µm s^–1 found for ³²P-transport.There was no indication of intercellular translocation at avelocity faster than visible streaming. Cytochalasin B inhibitedthe translocation of ³²P and cytoplasmic streaming. CytochalasinB becomes fully effective in inhibiting streaming and transportafter an incubation time of at least 5 h. Key words: Chara hispida, Cytoplasmic streaming, Intercellular transport     

K+ supplementation increases muscle [Na+-K+-ATPase] and improves extrarenal K+ homeostasis in rats

Bundgaard, Henning, Thomas A. Schmidt, Jim S. Larsen, andKeld Kjeldsen. K⁺supplementation increases muscle[Na⁺-K⁺-ATPase]and improves extrarenal K⁺homeostasis in rats. J. Appl. Physiol.82(4): 1136-1144, 1997.Effects ofK⁺ supplementation (~200 mmolKCl/100 g chow) on plasma K⁺,K⁺ content, andNa⁺-K⁺-adeonsinetriphosphatase(ATPase) concentration([Na⁺-K⁺-ATPase])in skeletal muscles as well as on extrarenalK⁺ clearance were evaluated inrats. After 2 days of K⁺supplementation, hyperkalemia prevailed(K⁺-supplemented vs.weight-matched control animals) [5.1 ± 0.2 (SE) vs. 3.2 ± 0.1 mmol/l, P < 0.05, n = 5-6], and after 4 daysa significant increase in K⁺content was observed in gastrocnemius muscle (104 ± 2 vs. 97 ± 1 µmol/g wet wt, P < 0.05, n = 5-6). After 7 days ofK⁺ supplementation, a significantincrease in[³H]ouabain bindingsite concentration (344 ± 5 vs. 239 ± 8 pmol/g wet wt,P < 0.05, n = 4) was observed in gastrocnemiusmuscle. After 2 wk, increases in plasmaK⁺,K⁺ content, and[³H]ouabain bindingsite concentration in gastrocnemius muscle amounted to 40, 8, and 68%(P < 0.05) above values observed inweight-matched control animals, respectively. The latter change wasconfirmed by K⁺-dependentp-nitrophenyl phosphatase activitymeasurements. Fasting for 1 day reduced plasmaK⁺ andK⁺ content in gastrocnemius musclein rats that had been K⁺supplemented for 2 wk by 3.1 ± 0.3 mmol/l(P < 0.05, n = 5) and 15 ± 2 µmol/g wet wt(P < 0.05, n = 5), respectively. After induction of anesthesia, arterial plasma K⁺was measured during intravenous KCl infusion (0.75 mmolKCl · 100 g bodywt¹ · h¹).The K⁺-supplemented fasted groupdemonstrated a 42% (P < 0.05) lower plasma K⁺ rise, associated with asignificantly higher increase inK⁺ content in gastrocnemius muscleof 7 µmol/g wet wt (P < 0.05, n = 5) compared with their controlanimals. In conclusion, K⁺supplementation increases plasmaK⁺,K⁺ content, and[Na⁺-K⁺-ATPase]in skeletal muscles and improves extrarenalK⁺ clearance capacity.

     

Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike performance over 100km

Madsen, Klavs, Dave A. MacLean, Bente Kiens, and DirkChristensen. Effects of glucose, glucose plus branched-chain aminoacids, or placebo on bike performance over 100 km. J. Appl. Physiol. 81(6): 2644-2650, 1996.This studywas undertaken to determine the effects of ingesting either glucose(trial G) or glucose plusbranched-chain amino acids (BCAA; trialB), compared with placebo (trialP), during prolonged exercise. Nine well-trained cyclists with a maximal oxygen uptake of 63.1 ± 1.5 mlO₂ ^· min^{1 ·} kg¹performed three laboratory trials consisting of 100 km of cycling separated by 7 days between each trial. During these trials, the subjects were encouraged to complete the 100 km as fast as possible ontheir own bicycles connected to a magnetic brake. No differences inperformance times were observed between the three trials (160.1 ± 4.1, 157.2 ± 4.5, and 159.8 ± 3.7 min, respectively). Intrial B, plasma BCAA levels increased from339 ± 28 µM at rest to 1,026 ± 62 µM after exercise(P < 0.01). Plasma ammoniaconcentrations increased during the entire exercise period for allthree trials and were significantly higher intrial B compared withtrials G andP (P < 0.05). The respiratory exchange ratio was similar in the threetrials during the first 90 min of exercise; thereafter, it tended todrop more in trial P than intrials G andB. These data suggest that neitherglucose nor glucose plus BCAA ingestion during 100 km of cyclingenhance performance in well-trained cyclists.

     

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.

     

Interrelationship of oxidative metabolism and local perfusion demonstrated by NMR in human skeletal muscle

Toussaint, Jean-François, Kenneth K. Kwong, FidelisM'Kparu, Robert M. Weisskoff, Paul J. LaRaia, and Howard L. Kantor. Interrelationship of oxidative metabolism and local perfusion demonstrated by NMR in human skeletal muscle. J. Appl.Physiol. 81(5): 2221-2228, 1996.Using nuclearmagnetic resonance (NMR), we have examined the relationship ofhigh-energy phosphate metabolism and perfusion in human soleus andgastrocnemius muscles. With ³¹P-NMR spectroscopy, we monitoredphosphocreatine (PCr) decay and recovery in eight normal volunteers andfour heart failure patients performing ischemic plantar flexion. Byusing echo-planar imaging, perfusion was independently measured by alocal [inversion-recovery (T1-flow)] and a regionaltechnique (NMR-plethysmography). After correction for its pHdependence, PCr recovery time constant is 27.5 ± 8.0 s innormal volunteers, with mean flow 118 ± 75 (soleus andgastrocnemius T1-flow) and 30.2 ± 9.7 ml ^· 100 ml^{1 ·} min¹(NMR-plethysmography-flow). We demonstrate a positive correlation between PCr time constant and local perfusion given byy = 50  0.15x(r² = 0.68, P = 0.01) for the 8 normal subjects,and y = 64  0.24x (r² = 0.83, P = 0.0001) for the 12 subjectsrecruited in the study. Regional perfusion techniques also show asignificant but weaker correlation. Using this totally noninvasivemethod, we conclude that aerobic ATP resynthesis is related to themagnitude of perfusion, i.e., O₂availability, and demonstrate that magnetic resonance imaging andmagnetic resonance spectroscopy together can accurately assess musclefunctional status.

     

Effects of hindlimb contraction on pressor and muscle interstitial metabolite responses in the cat

We used the microdialysis technique to measurethe interstitial concentration of several putative metabolic stimulantsof the exercise pressor reflex during 3- and 5-Hz twitch contractions in the decerebrate cat. The peak increases in heart rate and mean arterial pressure during contraction were 20 ± 5 beats/min and 21 ± 8 mmHg and 27 ± 9 beats/min and 37 ± 12 mmHg for the 3- and 5-Hz stimulation protocols, respectively. All variables returned tobaseline after 10 min of recovery. Interstitial lactate rose (P < 0.05) by 0.41 ± 0.15 and0.56 ± 0.16 mM for the 3- and 5-Hz stimulation protocols,respectively, and were not statistically different from one another.Interstitial lactate levels remained above(P < 0.05) baseline during recoveryin the 5-Hz group. Dialysate phosphate concentrations (corrected forshifts in probe recovery) rose with stimulation(P < 0.05) by 0.19 ± 0.08 and0.11 ± 0.03 mM for the 3- and 5-Hz protocols. There were nodifferences between groups. The resting dialysateK⁺ concentrations for the 3- and5-Hz conditions were 4.0 ± 0.1 and 3.9 ± 0.1 meq/l,respectively. During stimulation the dialysate K⁺ concentrations rose steadilyfor both conditions, and the increase from rest to stimulation(P < 0.05) was 0.57 ± 0.19 and0.81 ± 0.06 meq/l for the 3- and 5-Hz conditions, respectively,with no differences between groups. Resting dialysate pH was6.915 ± 0.055 and 6.981 ± 0.032 and rose to 7.013 (P < 0.05) and 7.053 (P < 0.05) for the 3- and 5-Hzconditions, respectively, and then became acidotic (6.905, P < 0.05) during recovery (5 Hzonly). This study represents the first time simultaneous measurements of multiple skeletal muscle interstitial metabolites and pressor responses to twitch contractions have been made in the cat. These datasuggest that interstitial K⁺ andphosphate, but not lactate and H⁺,may contribute to the stimulation of thin fiber muscle afferents duringcontraction.

     

Measurement of pulmonary blood flow by fractal analysis of flow heterogeneity in isolated canine lungs

Barman, Scott A., Laryssa L. McCloud, John D. Catravas, andIna C. Ehrhart. Measurement of pulmonary blood flow by fractalanalysis of flow heterogeneity in isolated canine lungs. J. Appl. Physiol. 81(5):2039-2045, 1996.Regional heterogeneity of lung blood flow can bemeasured by analyzing the relative dispersion (RD) of mass(weight)-flow data. Numerous studies have shown that pulmonary bloodflow is fractal in nature, a phenomenon that can be characterized bythe fractal dimension and the RD for the smallest realizable volumeelement (piece size). Although information exists for theapplicability of fractal analysis to pulmonary blood flow in wholeanimal models, little is known in isolated organs. Therefore, thepresent study was done to determine the effect of blood flow rate onthe distribution of pulmonary blood flow in the isolated blood-perfusedcanine lung lobe by using fractal analysis. Four different radiolabeledmicrospheres (¹⁴¹Ce,⁹⁵Nb,⁸⁵Sr, and⁵¹Cr), each 15 µm in diameter,were injected into the pulmonary lobar artery of isolated canine lunglobes (n = 5) perfused at fourdifferent flow rates ( flow1 = 0.42 ± 0.02 l/min;flow2 = 1.12 ± 0.07 l/min;flow 3 = 2.25 ± 0.17 l/min; flow 4 = 2.59 ± 0.17 l/min), and the pulmonary blood flow distribution was measured. Theresults of the present study indicate that under isogravimetric bloodflow conditions, all regions of horizontally perfused isolated lunglobes received blood flow that was preferentially distributed to themost distal caudal regions of the lobe. Regional pulmonary blood flowin the isolated perfused canine lobe was heterogeneous and fractal innature, as measured by the RD. As flow rates increased, fractal dimension values (averaging 1.22 ± 0.08) remained constant, whereas RD decreased, reflecting more homogeneous blood flowdistribution. At any given blood flow rate, high-flow areas of the lobereceived a proportionally larger amount of regional flow, suggestingthat the degree of pulmonary vascular recruitment may also be spatially related.

     

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.

     

Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training

McCall, G. E., W. C. Byrnes, A. Dickinson, P. M. Pattany,and S. J. Fleck. Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training.J. Appl. Physiol. 81(5):2004-2012, 1996.Twelve male subjects with recreationalresistance training backgrounds completed 12 wk of intensifiedresistance training (3 sessions/wk; 8 exercises/session; 3 sets/exercise; 10 repetitions maximum/set). All major muscle groupswere trained, with four exercises emphasizing the forearm flexors.After training, strength (1-repetition maximum preacher curl) increasedby 25% (P < 0.05). Magneticresonance imaging scans revealed an increase in the biceps brachiimuscle cross-sectional area (CSA) (from 11.8 ± 2.7 to 13.3 ± 2.6 cm²;n = 8;P < 0.05). Muscle biopsies of thebiceps brachii revealed increases(P < 0.05) in fiber areas for type I(from 4,196 ± 859 to 4,617 ± 1,116 µm²;n = 11) and II fibers (from 6,378 ± 1,552 to 7,474 ± 2,017 µm²;n = 11). Fiber number estimated fromthe above measurements did not change after training (293.2 ± 61.5 × 10³ pretraining; 297.5 ± 69.5 × 10³ posttraining;n = 8). However, the magnitude ofmuscle fiber hypertrophy may influence this response because thosesubjects with less relative muscle fiber hypertrophy, but similarincreases in muscle CSA, showed evidence of an increase in fibernumber. Capillaries per fiber increased significantly(P < 0.05) for both type I(from 4.9 ± 0.6 to 5.5 ± 0.7;n = 10) and II fibers (from 5.1 ± 0.8 to 6.2 ± 0.7; n = 10). Nochanges occurred in capillaries per fiber area or muscle area. Inconclusion, resistance training resulted in hypertrophy of the totalmuscle CSA and fiber areas with no change in estimated fiber number,whereas capillary changes were proportional to muscle fiber growth.

     

Conservation of bronchiolar wall area during constriction and dilation of human airways

Mitchell, R. W., E. Rühlmann, H. Magnussen, N. M. Muñoz, A. R. Leff, and K. F. Rabe. Conservation ofbronchiolar wall area during constriction and dilation of humanairways. J. Appl. Physiol. 82(3):954-958, 1997.We assessed the effect of smooth musclecontraction and relaxation on airway lumen subtended by the internalperimeter(A_i)and total cross-sectional area (A_o)of human bronchial explants in the absence of the potential lungtethering forces of alveolar tissue to test the hypothesis thatbronchoconstriction results in a comparable change ofA_i andA_o.Luminal area (i.e.,A_i) andA_owere measured by using computerized videomicrometry, and bronchial wallarea was calculated accordingly. Images on videotape were captured;areas were outlined, and data were expressed as internal pixel numberby using imaging software. Bronchial rings were dissected in 1.0- to1.5-mm sections from macroscopically unaffected areas of lungs frompatients undergoing resection for carcinoma, placed in microplate wellscontaining buffered saline, and allowed to equilibrate for 1 h.Baseline, A_o[5.21 ± 0.354 (SE)mm²], andA_i(0.604 ± 0.057 mm²) weremeasured before contraction of the airway smooth muscle (ASM) withcarbachol. MeanA_inarrowed by 0.257 ± 0.052 mm²in response to 10 µM carbachol (P = 0.001 vs. baseline). Similarly, A_onarrowed by 0.272 ± 0.110 mm²in response to carbachol (P = 0.038 vs. baseline; P = 0.849 vs. change inA_i).Similar parallel changes in cross-sectional area forA_iandA_owere observed for relaxation of ASM from inherent tone of otherbronchial rings in response to 10 µM isoproterenol. We demonstrate aunique characteristic of human ASM; i.e., both luminal and totalcross-sectional area of human airways change similarly on contractionand relaxation in vitro, resulting in a conservation of bronchiolarwall area with bronchoconstriction and dilation.