Greater airway narrowing in immature than in mature rabbits during methacholine challenge

Shen, X., V. Bhargava, G. R. Wodicka, C. M. Doerschuk, S. J. Gunst, and R. S. Tepper. Greater airway narrowing in immature thanin mature rabbits during methacholine challenge. J. Appl. Physiol. 81(6): 2637-2643, 1996.It hasbeen demonstrated that methacholine (MCh) challenge produces a greaterincrease in lung resistance in immature than in mature rabbits (R. S. Tepper, X. Shen, E. Bakan, and S. J. Gunst.J. Appl. Physiol. 79: 1190-1198, 1995). To determine whether this maturational difference in the response to MCh was primarily related to changes in airway resistance (Raw) or changes in tissue resistance, we assessed airway narrowing in1-, 2-, and 6-mo-old rabbits during intravenous MCh challenge (0.01-5.0 mg/kg). Airway narrowing was determined frommeasurements of Raw in vivo and from morphometric measurements on lungsections obtained after rapidly freezing the lung after the MChchallenge. The fold increase in Raw was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. Similarly, the degree of airway narrowing assessed morphometrically was significantly greaterfor 1- and 2-mo-old animals than for 6-mo-old animals. The foldincrease in Raw was highly correlated with the degree of airwaynarrowing assessed morphometrically(r² = 0.82, P < 0.001). We conclude that thematurational difference in the effect of MCh on lung resistance isprimarily caused by greater airway narrowing in the immature rabbits.

     

Postnatal lung function and protein permeability after fetal or maternal corticosteroids in preterm lambs

Rebello, Celso M., Machiko Ikegami, M. Gore Ervin, Daniel H. Polk, and Alan H. Jobe. Postnatal lung function and protein permeability after fetal or maternal corticosteroids in preterm lambs.J. Appl. Physiol. 83(1): 213-218, 1997.We evaluated postnatal lung function andintravascular albumin loss to tissues of 123-days-gestation pretermsurfactant-treated and ventilated lambs 15 h after direct fetal(n = 8) or maternal(n = 9) betamethasone treatment orsaline placebo (n = 9). Thebetamethasone-treated groups had similar increases in dynamiccompliances, ventilatory efficiency indexes, and lung volumes relativeto controls (P < 0.05). The lossesof ¹²⁵I-labeled albumin fromblood, a marker of intravascular integrity, and the recoveries of¹²⁵I-albumin in muscle and brainwere similar for control and betamethasone-exposed lambs.Betamethasone-treated lambs had lower recoveries of¹²⁵I-albumin in lung tissues andin alveolar washes than did controls (P < 0.01). Although blood pressureswere higher for the treated groups (P < 0.05), all groups had similar blood volumes, cardiac outputs, andorgan blood flows. Maternal or fetal treatment with betamethasone 15 hbefore preterm delivery equivalently improved postnatal lung function,reduced albumin recoveries in lungs, and increased blood pressures.However, prenatal betamethasone had no effects on the systemicintravascular losses of albumin or did not change blood volumes.

     

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.

     

Diaphragm thickening during inspiration

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

     

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.

     

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity

Verbanck, Sylvia, Hans Larsson, Dag Linnarsson, G. KimPrisk, John B. West, and Manuel Paiva. Pulmonary tissue volume, cardiac output and diffusing capacity in sustained microgravity. J. Appl. Physiol. 83(3): 810-816, 1997.In microgravity (µG) humans have marked changes in bodyfluids, with a combination of an overall fluid loss and aredistribution of fluids in the cranial direction. We investigatedwhether interstitial pulmonary edema develops as a result of a headwardfluid shift or whether pulmonary tissue fluid volume is reduced as aresult of the overall loss of body fluid. We measured pulmonary tissuevolume (Vti), capillary blood flow, and diffusing capacity in foursubjects before, during, and after 10 days of exposure to µG duringspaceflight. Measurements were made by rebreathing a gas mixturecontaining small amounts of acetylene, carbon monoxide, and argon.Measurements made early in flight in two subjects showed no change inVti despite large increases in stroke volume (40%) and diffusingcapacity (13%) consistent with increased pulmonary capillary bloodvolume. Late in-flight measurements in four subjects showed a 25%reduction in Vti compared with preflight controls(P < 0.001). There was aconcomittant reduction in stroke volume, to the extent that it was nolonger significantly different from preflight control. Diffusingcapacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despiteincreased pulmonary perfusion and pulmonary capillary blood volume,interstitial pulmonary edema does not result from exposure to µG.

     

Nitric oxide decreases lung liquid production in fetal lambs

Cummings, James J. Nitric oxide decreases lung liquidproduction in fetal lambs. J. Appl.Physiol. 83(5): 1538-1544, 1997.To examine theeffect of nitric oxide on fetal lung liquid production, I measured lungliquid production in fetal sheep at 130 ± 5 days gestation (range122-137 days) before and after intrapulmonary instillation ofnitric oxide. Thirty-one studies were done in which net lung luminalliquid production (Jv) was measured by plotting the change in lung luminal liquid concentration ofradiolabeled albumin, an impermeant tracer that was mixed into the lungliquid at the start of each study. To see whether changes inJvmight be associated with changes in pulmonary hemodynamics, pulmonary and systemic pressures were measured and left pulmonary arterial flowwas measured by an ultrasonic Doppler flow probe. Variables weremeasured during a 1- to 2-h control period and for 4 h after a smallbolus of isotonic saline saturated with nitric oxide gas (10 or 100%)was instilled into the lung liquid. Control (saline) instillations(n = 6) caused no change in anyvariable over 6 h. Nitric oxide instillation significantly decreasedJv and increased pulmonary blood flow;these effects were sustained for 1-2 h. There was also asignificant but transient decrease in pulmonary arterial pressure. Thusintrapulmonary nitric oxide causes a significant decrease in lungliquid and is associated with a decrease in pulmonary vascularresistance. In a separate series of experiments either amiloride orbenzamil, which blocks Na⁺transport, was mixed into the lung liquid before nitric oxide instillation; still, there was a similar reduction in lung liquid production. Thus the reduction in lung liquid secretion caused bynitric oxide does not appear to depend on apicalNa⁺ efflux.

     

Redistribution of pulmonary blood flow during unilateral hypoxia in prone and supine dogs

We usedfluorescent-labeled microspheres in pentobarbital-anesthetized dogs tostudy the effects of unilateral alveolar hypoxia on the pulmonary bloodflow distribution. The left lung was ventilated with inspiredO₂ fraction of 1.0, 0.09, or 0.03 in random order; the right lung was ventilated with inspiredO₂ fraction of 1.0. The lungs wereremoved, cleared of blood, dried at total lung capacity, then cubed toobtain ~1,500 small pieces of lung (~1.7 cm³). The coefficient ofvariation of flow increased (P < 0.001) in the hypoxic lung but was unchanged in the hyperoxic lung.Most (70-80%) variance in flow in the hyperoxic lung wasattributable to structure, in contrast to only 30-40% of thevariance in flow in the hypoxic lung(P < 0.001). When adjusted for thechange in total flow to each lung, 90-95% of the variance in thehyperoxic lung was attributable to structure compared with 70-80%in the hypoxic lung (P < 0.001). Thehilar-to-peripheral gradient, adjusted for change in total flow,decreased in the hypoxic lung (P = 0.005) but did not change in the hyperoxic lung. We conclude thathypoxic vasoconstriction alters the regional distribution of flow inthe hypoxic, but not in the hyperoxic, lung.

     

Lung liquid production rates and volumes do not decrease before labor in healthy fetal sheep

Lines, A., S. B. Hooper, and R. Harding. Lung liquidproduction rates and volumes do not decrease before labor in healthy fetal sheep. J. Appl. Physiol. 82(3):927-932, 1997.Previous studies have suggested that the volumeand production rate of fetal lung liquid decrease late in gestation,before the onset of labor, in preparation for the clearance of lungliquid at birth. In contrast, our earlier studies have not shown adecrease in lung liquid volume near term, although these studies werenot continued to the onset of labor. Our aim was to determine the changes in lung liquid volume and production rate in fetal sheep duringthe last 2 wk of gestation up to the onset of labor at term (~147days). In eight chronically catheterized fetal sheep, the volume andproduction rate of fetal lung liquid were measured at 130, 135, and 140 days of gestation and then on every 2nd day until the onset oflabor. Labor was detected by monitoring uterine muscleactivity and intrauterine pressure changes. On the day of labor onset,which occurred at 147 ± 1 days of gestation, fetuses weighed 5.0 ± 0.2 kg. The volume of fetal lung liquid was 40.4 ± 2.7 ml/kgat 19 ± 1 days before labor onset and had not significantly changedby 0.7 ± 0.2 days (44.8 ± 5.1 ml/kg) before labor. Similarly, lung liquid production rates at 19 ± 1 days before labor (5.1 ± 1.8 ml ^· h^{1 ·} kg¹)were not significantly different from those at 0.7 ± 0.2 days before labor (3.4 ± 0.7 ml ^· h^{1 ·} kg¹).We conclude that, in healthy ovine fetuses, lung liquid volumes andproduction rates do not decrease before the onset of labor. Our resultsindicate that the entire volume of fetal lung liquid (~222.5 ± 36.6 ml) must be cleared after the onset of labor.

     

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.

     

Retention of soluble 99mTc-DTPA in the human lung: 24-h postdeposition

Foster, W. Michael, Pamela T. Stetkiewicz, and Arthur N. Freed. Retention of soluble^99mTc-DTPA in the human lung: 24-hpostdeposition. J. Appl. Physiol. 82(4): 1378-1382, 1997.Clearance of low-molecular-weightsolutes, e.g., radiolabeled chelate diethylenetriaminepentaacetate(DTPA), across epithelial surfaces of distal airways and the lungparenchyma is a broadly used technique to assess epithelial integrity.It has been generally assumed that clearance of solute follows a simplefirst-order process and that DTPA clearance through the respiratoryepithelium and into blood and lymphatic channels is complete within afew hours. Using -camera imaging and a radiolabeled aerosol of^99mTc-labeled DTPA, we observed ineight healthy subjects lung retention of radioisotope ~24 hpostdeposition of the ^99mTc-DTPA.Residual lung retention at the 24-h end point averaged 6.0 ± 1.8 (SD)% of the amount of radioisotope initially deposited in the lung.This suggests that for normal healthy subjects a small amount of the^99mTc radioisotope, either in adissociated or chelated form, is nonpermeable or slowly cleared fromrespiratory tisssues.

     

Gender differences in airway resistance during sleep

Trinder, John, Amanda Kay, Jan Kleiman, and Judith Dunai.Gender differences in airway resistance during sleep.J. Appl. Physiol. 83(6):1986-1997, 1997.At the onset of non-rapid-eye-movement (NREM)sleep there is a fall in ventilation and an increase in upper airwayresistance (UAR). In healthy men there is a progressive increase in UARas NREM sleep deepens. This study compared the pattern of change in UARand ventilation in 14 men and 14 women (aged 18-25 yr) both duringsleep onset and over the NREM phase of a sleep cycle (from wakefulnessto slow-wave sleep). During sleep onset, fluctuations betweenelectroencephalographic alpha and theta activity were associated withmean alterations in inspiratory minute ventilation and UAR of between 1 and 4.5 l/min and between 0.70 and 5.0 cmH₂O · l¹ · s,respectively, with no significant effect of gender on either change(P > 0.05). During NREM sleep,however, the increment in UAR was larger in men than in women(P < 0.01), such that the meanlevels of UAR at peak flow reached during slow-wave sleep were ~25and 10 cmH₂O · l¹ · sin men and women, respectively. We speculate that the greater increasein UAR in healthy young men may represent a gender-related susceptibility to sleep-disordered breathing that, in conjunction withother predisposing factors, may contribute to the development ofobstructive sleep apnea.

     

Regional measurements of pulmonary edema by using magnetic resonance imaging

Athree-dimensional magnetic resonance imaging (MRI) method to measurepulmonary edema and lung microvascular barrier permeability wasdeveloped and compared with conventional methods in nine mongrel dogs.MRIs were obtained covering the entire lungs. Injury was induced byinjection of oleic acid (0.021-0.048 ml/kg) into a jugularcatheter. Imaging followed for 0.75-2 h. Extravascular lung waterand permeability-related parameters were measured from multiple-indicator dilution curves. Edema was measured as magnetic resonance signal-to-noise ratio (SNR). Postinjury wet-to-dry lung weight ratio was 5.30 ± 0.38 (n = 9). Extravascular lung water increased from 2.03 ± 1.11 to 3.00 ± 1.45 ml/g(n = 9, P < 0.01). Indicatordilution studies yielded parameters characterizing capillary exchangeof urea and butanediol: the product of the square root of equivalentdiffusivity of escape from the capillary and capillary surface area(D^1/2S)and the capillary permeability-surface area product(PS). The ratio ofD^1/2Sfor urea toD^1/2Sfor butanediol increased from 0.583 ± 0.027 to 0.852 ± 0.154 (n = 9, P < 0.05). Whole lung SNR atbaseline, before injury, correlated withD^1/2Sand PS ratios (both P < 0.02). By using rate of SNR change, the mismatch of transcapillaryfiltration flow and lymph clearance was estimated to be0.2-1.8 ml/min. The filtration coefficient was estimated fromthese values. Results indicate that pulmonary edema formation duringoleic acid injury can be imaged regionally and quantified globally, andthe results suggest possible regional quantification by usingthree-dimensional MRI.

     

Effect of tidal volume and frequency on airway responsiveness in mechanically ventilated rabbits

Shen, X., S. J. Gunst, and R. S. Tepper. Effect oftidal volume and frequency on airway responsiveness in mechanically ventilated rabbits. J. Appl. Physiol.83(4): 1202-1208, 1997.We evaluated the effects of the rate andvolume of tidal ventilation on airway resistance (Raw) duringintravenous methacholine (MCh) challenge in mechanically ventilatedrabbits. Five rabbits were challenged at tidal volumes of 5, 10, and 20 ml/kg at a frequency of 15 breaths/min and also under static conditions(0 ml/kg tidal volume). Four rabbits were subjected to MCh challenge atfrequencies of 6 and 30 breaths/min with a tidal volume of 10 ml/kg andalso under static conditions. In both groups, the increase in Raw with MCh challenge was significantly greater under static conditions thanduring tidal ventilation at any frequency or volume. Increases in thevolume or frequency of tidal ventilation resulted in significant decreases in Raw in response to MCh. We conclude that tidal breathing suppresses airway responsiveness in rabbits in vivo. The suppression ofnarrowing in response to MCh increases as the magnitude of the volumeor the frequency of the tidal oscillations is increased. Our findingssuggest that the effect of lung volume changes on airway responsivenessin vivo is primarily related to the stretch of airway smooth muscle.

     

Measurement of tidal volume by using transthoracic impedance variations in rats

Theapplication of impedance pneumography for monitoring respiration insmall animals has been limited by problems withcalibration. With improved instrumentation, we describethe calibration of tidal volume in anesthetized rats. The detection ofchanges in voltage, reflecting the electrical impedance variationsassociated with respiration, was optimized by using disposable adhesivesilver-silver chloride electrodes, advanced circuitry, andanalog-to-digital recording instrumentation. We found a linearrelationship between change in impedance and tidal volume in individualrats (R²  98%), which was strongly influenced by rat weight. Consequently, acalibration equation incorporating change in impedance and rat weightwas derived to predict tidal volume. Comparison of the predicted andtrue tidal volumes revealed a meanR²  98%,slopes of ~1, intercepts of ~0, and bias of ~0.07 ml. Thepredicted volumes were not significantly affected by either frequencyof respiration or pulmonary edema. We conclude that impedancepneumography provides a valuable tool for the noninvasive measurementof tidal volume in anesthetized rats.     

Partial liquid ventilation protects lung during resuscitation from shock

Younger, John G., Ali S. Taqi, Gerd O. Till, and Ronald B. Hirschl. Partial liquid ventilation protects lung during resuscitation from shock. J. Appl.Physiol. 83(5): 1666-1670, 1997.Preliminaryanimal experience with partial liquid ventilation (PLV) suggests thatthis therapy may diminish neutrophil invasion and capillary leak duringacute lung injury. We sought to confirm these findings in a model ofshock-induced lung injury. Sixty anesthetized rats were studied. Afterhemorrhage to an arterial pressure of 25 mmHg for 45 min, animals wereresuscitated with blood and saline and treated with gas ventilationalone or with 5 ml/kg of intratracheally administered perflubron.Myeloperoxidase activity was used to measure lung neutrophil content. Apermeability index (the bronchoalveolar-to-blood ratio of¹²⁵I-labeled albumin activity)quantified alveolar leak. Injury caused an increase in myeloperoxidasethat was reversed by PLV (injury = 0.837 ± 0.452, PLV = 0.257 ± 0.165; P < 0.01). Capillary permeability also increased withhemorrhage, with a strong trend toward improvement in the PLV group(permeability indexes: injury = 0.094 ± 0.102, PLV = 0.045 ± 0.045; 95% confidence interval for injury  PLV: 0.024,0.1219). We conclude that PLV is associated with a decrease inpulmonary neutrophil accumulation and a trend toward decreased capillary leak after hemorrhagic shock.

     

Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart

Osborn, Brett A., June T. Daar, Richard A. Laddaga, Fred D. Romano, and Dennis J. Paulson. Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart. J. Appl. Physiol. 82(3): 828-834, 1997.This study determined whether dynamic exercise training ofdiabetic rats would increase the expression of the GLUT-4 glucosetransport protein in prepared cardiac sarcolemmal membranes. Fourgroups were compared: sedentary control, sedentary diabetic, trainedcontrol, and trained diabetic. Diabetes was induced by intravenousstreptozotocin (60 mg/kg). Trained control and diabetic rats were runon a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk.Sarcolemmal membranes were isolated by using differentialcentrifugation, and the activity of sarcolemmalK⁺-p-nitrophenylphosphatase( pNPPase; an indicator ofNa⁺-K⁺-adenosinetriphosphataseactivity) was quantified. Hearts from the sedentary diabetic groupexhibited a significant depression of sarcolemmal pNPPaseactivity. Exercise training did not significantly alterpNPPase activity. Sedentary diabetic rats exhibited an 84 and 58% decrease in GLUT-4 protein and mRNA, respectively, relative tocontrol rats. In the trained diabetic animals, sarcolemmal GLUT-4protein levels were only reduced by 50% relative to control values,whereas GLUT-4 mRNA were returned to control levels. The increase inmyocardial sarcolemmal GLUT-4 may be beneficial to the diabetic heartby enhancing myocardial glucose oxidation and cardiac performance

     

Respiratory impedances and acinar gas transfer in a canine model for emphysema

Barnas, George M., Paul A. Delaney, Ileana Gheorghiu,Srinivas Mandava, Robert G. Russell, Renée Kahn, and Colin F. Mackenzie. Respiratory impedances and acinar gas transfer in acanine model for emphysema. J. Appl.Physiol. 83(1): 179-188, 1997.We examined howthe changes in the acini caused by emphysema affected gas transfer outof the acinus (T_aci) and lungand chest wall mechanical properties. Measurements were taken from fivedogs before and 3 mo after induction of severe bilateral emphysema byexposure to papain aerosol (170-350 mg/dose) for 4 consecutive wk.With the dogs anesthetized, paralyzed, and mechanically ventilated at0.2 Hz and 20 ml/kg, we measuredT_aci by the rate of washout of¹³³Xe from an area of the lungwith occluded blood flow. Measurements were repeated at positiveend-expiratory pressures (PEEP) of 10, 5, 15, 0, and 20 cmH₂O. We also measured dynamicelastances and resistances of the lungs(EL andRL, respectively) and chest wall at the different PEEP and during sinusoidal forcing in the normal rangeof breathing frequency and tidal volume. After final measurements, tissue sections from five randomly selected areas of the lung eachshowed indications of emphysema.T_aci during emphysema was similarto that in control dogs. ELdecreased by ~50% during emphysema (P < 0.05) but did not change itsdependence on frequency or tidal volume.RL did not change(P > 0.05) at the lowest frequencystudied (0.2 Hz), but in some dogs it increased compared with control at the higher frequencies. Chest wall properties were not changed byemphysema (P > 0.05). We suggestthat although large changes in acinar structure andEL occur during uncomplicatedbilateral emphysema, secondary complications must be present to causeseveral of the characteristic dysfunctions seen in patients withemphysema.

     

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.

     

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.