Methacholine causes reflex bronchoconstriction

To determine whether methacholine causes vagally mediated reflexconstriction of airway smooth muscle, we administered methacholine tosheep either via the bronchial artery or as an aerosol via tracheostomyinto the lower airways. We then measured the contraction of anisolated, in situ segment of trachealis smooth muscle and determinedthe effect of vagotomy on the trachealis response. Administeringmethacholine to the subcarinal airways via the bronchial artery(0.5-10.0 µg/ml) caused dose-dependent bronchoconstriction andcontraction of the tracheal segment. At the highest methacholine concentration delivered, trachealis smooth muscle tension increased anaverage of 186% over baseline. Aerosolized methacholine (5-7 breaths of 100 mg/ml) increased trachealis tension by 58% and airwaysresistance by 183%. As the bronchial circulation in the sheep does notsupply the trachea, we postulated that the trachealis contraction wascaused by a reflex response to methacholine in the lower airways.Bilateral vagotomy essentially eliminated the trachealis response andthe airways resistance change after lower airways challenge (either viathe bronchial artery or via aerosol) with methacholine. We concludethat 1) methacholine causes asubstantial reflex contraction of airway smooth muscle and2) the assumption may not be validthat a response to methacholine in humans or experimental animalsrepresents solely the direct effect on smooth muscle.

     

Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction

Charan, Nirmal B., and Paula Carvalho. Angiogenesis inbronchial circulatory system after unilateral pulmonary artery obstruction. J. Appl. Physiol. 82(1):284-291, 1997.We studied the effects of left pulmonary artery(LPA) ligation on the bronchial circulatory system (BCS) by using asheep model. LPA was ligated in the newborn lambs soon after birth(n = 8), and when the sheep were ~3yr of age anatomic studies revealed marked angiogenesis in BCS.Bronchial blood flow and cardiac output were studied by placing flowprobes around the bronchial and pulmonary arteries in four adult sheep.After LPA ligation, bronchial blood flow increased from 35 ± 6 to134 ± 42 ml/min in ~3 wk (P < 0.05). We also studied gas-exchange functions of BCS ~3 yr after the ligation of LPA in newborn lambs (n = 4) and used a control group (n = 12)in which LPA was ligated acutely. In the left lung,O₂ uptake after acute ligation was16 ± 3 ml/min and was similar to the chronic model, whereasCO₂ output in the control group was 27 ± 3 ml/min compared with 79 ± 12 ml/min in the chronic preparation (P < 0.05).We conclude that LPA ligation causes marked angiogenesis in BCS that iscapable of performing some gas-exchange functions.

     

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.

     

Effects of edema on small airway narrowing

Wagner, Elizabeth M. Effects of edema on small airwaynarrowing. J. Appl. Physiol. 83(3):784-791, 1997.Numerous mediators of inflammation have beendemonstrated to cause airway microvascular fluid and proteinextravasation. That fluid extravasation results in airway wall edemaleading to airway narrowing and enhanced reactivity has not beenconfirmed. In anesthetized, ventilated sheep(n = 30), airway vascularfluid extravasation was induced by infusing bradykinin(10⁶ M) through acannulated, blood-perfused bronchial artery. Airway wall edema andluminal narrowing were determined morphometrically. Airway reactivityto methacholine (MCh; 10 µg/ml, intrabronchial artery) was determinedby measuring conducting airway resistance (Raw) by forced oscillation.Raw measurements were made and lung lobes were excised and quick frozenbefore or after a 1-h bradykinin infusion. In 10 airways per lobe(range 0.2- to 2.0-mm relaxed diameter), wall area occupied 32 ± 2% (SE) of the total normalized airway area(n = 9). Bradykinin infusion increasedwall area to 42 ± 5% (P = 0.02);luminal area decreased by <5%; and smooth muscle perimeter, ameasure of smooth muscle constriction, was not altered(n = 5). Raw showed nochange from baseline (1.4 ± 0.4 cmH₂O · l¹ · s)after bradykinin infusion (n = 10).During MCh challenge, Raw increased by 3.2 ± 04 cmH₂O · l¹ · s,and this change did not differ after administration of bradykinin. MChchallenge caused similar decreases in smooth muscle perimeter (10%)and luminal area (72 vs. 68%) before and after bradykinin infusion.However, the time constant of recovery of Raw from MCh constriction wasincreased from control (40 ± 3 s) to 57 ± 10 s after bradykinininfusion (P = 0.03). When lung lobeswere excised at the same time after MCh challenge was terminated(n = 5), luminal area was greaterbefore bradykinin infusion than after (86 vs. 78%;P = 0.007), as was smooth muscleperimeter. The results of this study demonstrate that airway wall edemalimits relaxation after induced constriction rather than enhancingconstriction.

     

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.

     

Augmentation of exercise-induced muscle sympathetic nerve activity during muscle heating

Ray, Chester A., and Kathryn H. Gracey. Augmentation ofexercise-induced muscle sympathetic nerve activity during muscle heating. J. Appl. Physiol. 82(6):1719-1725, 1997.The muscle metabo- and mechanoreflexes have beenshown to increase muscle sympathetic nerve activity (MSNA) duringexercise. Group III and IV muscle afferents, which are believed tomediate this response, have been shown to be thermosensitive inanimals. The purpose of the present study was to evaluate the effect ofmuscle temperature on MSNA responses during exercise. Eleven subjectsperformed ischemic isometric handgrip at 30% of maximal voluntarycontraction to fatigue, followed by 2 min of postexercise muscleischemia (PEMI), with and without local heating of the forearm. Localheating of the forearm increased forearm muscle temperature from 34.4 ± 0.2 to 38.9 ± 0.3°C(P = 0.001). Diastolic andmean arterial pressures were augmented during exercise in the heat.MSNA responses were greater during ischemic handgrip with local heatingcompared with control (no heating) after the first 30 s. MSNA responsesat fatigue were greater during local heating. MSNA increased by 16 ± 2 and 20 ± 2 bursts per 30 s for control and heating,respectively (P = 0.03). Whenexpressed as a percent change in total activity (total burstamplitude), MSNA increased 531 ± 159 and 941 ± 237% forcontrol and heating, respectively (P = 0.001). However, MSNA was not different during PEMI between trials.This finding suggests that the augmentation of MSNA during exercisewith heat was due to the stimulation of mechanically sensitive muscleafferents. These results suggest that heat sensitizes skeletal muscleafferents during muscle contraction in humans and may play a role inthe regulation of MSNA during exercise.

     

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.

     

Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans

Rådegran, G. Ultrasound Dopplerestimates of femoral artery blood flow during dynamic knee extensorexercise in humans. J. Appl. Physiol.83(4): 1383-1388, 1997.Ultrasound Doppler has been used tomeasure arterial inflow to a human limb during intermittent staticcontractions. The technique, however, has neither been thoroughlyvalidated nor used during dynamic exercise. In this study, the inherentproblems of the technique have been addressed, and the accuracy wasimproved by storing the velocity tracings continuously and calculatingthe flow in relation to the muscle contraction-relaxation phases. Thefemoral arterial diameter measurements were reproducible with a meancoefficient of variation within the subjects of 1.2 ± 0.2%. Thediameter was the same whether the probe was fixed or repositioned atrest (10.8 ± 0.2 mm) or measured during dynamic exercise. The bloodvelocity was sampled over the width of the diameter and the parabolicvelocity profile, since sampling in the center resulted in anoverestimation by 22.6 ± 9.1% (P < 0.02). The femoral arterial Doppler blood flow increased linearly(r = 0.997, P < 0.001) with increasing load [Doppler blood flow = 0.080 · load (W) + 1.446 l/min] and was correlated positively with simultaneousthermodilution venous outflow measurements(r = 0.996, P < 0.001). The two techniques werelinearly related (Doppler = thermodilution · 0.985 + 0.071 l/min; r = 0.996, P < 0.001), with a coefficient ofvariation of ~6% for both methods.

     

Changes in bronchial and pulmonary arterial blood flow with progressive tension pneumothorax

Carvalho, Paula, Jacob Hildebrandt, and Nirmal B. Charan.Changes in bronchial and pulmonary arterial blood flow with progressive tension pneumothorax. J. Appl.Physiol. 81(4): 1664-1669, 1996.We studied theeffects of unilateral tension pneumothorax and its release on bronchialand pulmonary arterial blood flow and gas exchange in 10 adultanesthetized and mechanically ventilated sheep with chronicallyimplanted ultrasonic flow probes. Right pleural pressure (Ppl) wasincreased in two steps from 5 to 10 and 25 cmH₂O and then decreased to 10 and5 cmH₂O. Each level of Pplwas maintained for 5 min. Bronchial blood flow, right and leftpulmonary arterial flows, cardiac output(T),hemodynamic measurements, and arterial blood gases were obtained at theend of each period. Pneumothorax resulted in a 66% decrease inT, bronchialblood flow decreased by 84%, and right pulmonary arterial flowdecreased by 80% at Ppl of 25 cmH₂O(P < 0.001). At peak Ppl, themajority ofT was due toblood flow through the left pulmonary artery. With resolution ofpneumothorax, hemodynamic parameters normalized, although abnormalitiesin gas exchange persisted for 60-90 min after recovery and wereassociated with a decrease in total respiratory compliance.

     

Nature and site of action of endogenous nitric oxide in vasculature of isolated pig lungs

Cremona, George, Tim Higenbottam, Motoshi Takao, Edward A. Bower, and Leslie W. Hall. Nature and site of action of endogenousnitric oxide in vasculature of isolated pig lungs. J. Appl. Physiol. 82(1): 23-31, 1997.The site ofaction of endogenous and exogenous nitric oxide (NO) in isolated piglungs was investigated by using arterial, double, and venous occlusion,which allowed precapillary, postcapillary, and venous segments to bepartitioned into arterial, precapillary, postcapillary, and venoussegments. N^G-nitro-L-arginine(L-NNA;10⁵ M) increased resistancein the arterial (35 ± 6.6%, P = 0.003), precapillary (39.3 ± 5.1%,P = 0.001), and venous (18.3 ± 4.8%, P = 0.01) segments,respectively. Sodium nitroprusside(10⁵ M) and NO (80 parts/million) reversed the effects ofL-NNA. Total pulmonary vascularresistance fell with increasing flow, due to a fall in precapillaryresistance and dynamic resistance, and was significantlylower than mean total resistance.L-NNA increased the resistancesbut did not alter the pattern of the pressure-flow relationships. It isconcluded that, in isolated pig lungs, the effect of endogenous NOseems to be dependent on flow in the arterial segment and independentof flow in the precapillary segment, but variation of its release doesnot appear to be fundamental to accommodation to changes in steadyflow.

     

Distribution of blood flow and neutrophil kinetics in bronchial vasculature of sheep

Baile, Elisabeth M., Peter D. Paré, David Ernest, andPeter M. Dodek. Distribution of blood flow and neutrophil kinetics in bronchial vasculature of sheep. J. Appl.Physiol. 82(5): 1466-1471, 1997.The bronchialcirculation, as opposed to the pulmonary circulation, is the likelysource of the edema and inflammatory cells that contribute to airflowobstruction and airway narrowing associated with asthma and pulmonaryedema. The purpose of this study was to understand the mechanism ofedema formation and inflammation in airway walls. Therefore, we soughtfirst to determine the normal bronchial venous drainage pathways. Inanesthetized, ventilated, open-chest sheep we measured the relativedistribution of ⁵¹Cr-labeled redblood cells to the right and left ventricles after injection into thebronchial artery (n = 7).Using this information, we then studied the kinetics of leukocytes inthe bronchial vascular bed. We measured the extraction of¹¹¹In-labeled neutrophils duringtheir first pass through the microvasculature after injection into thebronchial artery or right ventricle (n = 6). In the first set of experiments, we found >85% of the systemic blood flow to the lung returns to the left ventricle. In the second setof experiments, we found that extraction of neutrophils in thebronchial vasculature (50-60%) was less(P < 0.05) than that in thepulmonary vasculature (80%). This finding may be explained bydifferences in the anatomy and/or hydrodynamic dispersal forces between the pulmonary and bronchial vascular beds or may reflect sequestration of neutrophils within the pulmonary microvasculature while traversing bronchial-to-pulmonary anastomotic pathways.

     

Skeletal muscle ECF pH error signal for exercise ventilatory control

Evans, Allison B., Larry W. Tsai, David A. Oelberg, HomayounKazemi, and David M. Systrom. Skeletal muscle ECF pH error signalfor exercise ventilatory control. J. Appl.Physiol. 84(1): 90-96, 1998.An autonomic reflexlinking exercising skeletal muscle metabolism to central ventilatorycontrol is thought to be mediated by neural afferents having freeendings that terminate in the interstitial fluid of muscle. Todetermine whether changes in muscle extracellular fluid pH(pH_e) can provide an errorsignal for exercise ventilatory control,pH_e was measured duringelectrically induced contraction by³¹P-magnetic resonancespectroscopy and the chemical shift of a phosphorylated, pH-sensitivemarker that distributes to the extracellular fluid (phenylphosphonicacid). Seven lightly anesthetized rats underwentunilateral continuous 5-Hz sciatic nerve stimulation in an 8.45-Tnuclear magnetic resonance magnet, which resulted in a mixed lacticacidosis and respiratory alkalosis, with no net change in arterial pH.Skeletal muscle intracellular pH fell from 7.30 ± 0.03 units atrest to 6.72 ± 0.05 units at 2.4 min of stimulation and then roseto 7.05 ± 0.01 units (P < 0.05), despite ongoing stimulation and muscle contraction.Despite arterial hypocapnia, pH_eshowed an immediate drop from its resting baseline of 7.40 ± 0.01 to 7.16 ± 0.04 units (P < 0.05)and remained acidic throughout the stimulation protocol. During the on-and off-transients for 5-Hz stimulation, changes in the pH gradientbetween intracellular and extracellular compartments suggestedtime-dependent recruitment of sarcolemmal ion-transport mechanisms.pH_e of exercising skeletal musclemeets temporal and qualitative criteria necessary for a ventilatorymetaboreflex mediator in a setting where arterial pH doesnot.

     

Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic reflex

Ray, Chester A., and Keith M. Hume. Neck afferents andmuscle sympathetic activity in humans: implications for the vestibulosympathetic reflex. J. Appl.Physiol. 84(2): 450-453, 1998.We have shownpreviously that head-down neck flexion (HDNF) in humans elicitsincreases in muscle sympathetic nerve activity (MSNA). The purpose ofthis study was to determine the effect of neck muscle afferents onMSNA. We studied this question by measuring MSNA before and after headrotation that would activate neck muscle afferents but not thevestibular system (i.e., no stimulation of the otolith organs orsemicircular canals). After a 3-min baseline period with the head inthe normal erect position, subjects rotated their head to the side(~90°) and maintained this position for 3 min. Head rotation wasperformed by the subjects in both the prone(n = 5) and sitting(n = 6) positions. Head rotation did not elicit changes in MSNA. Average MSNA, expressed asburst frequency and total activity, was 13 ± 1 and 13 ± 1 bursts/min and 146 ± 34 and 132 ± 27 units/min during baselineand head rotation, respectively. There were no significant changes incalf blood flow (2.6 ± 0.3 to 2.5 ± 0.3 ml · 100 ml¹ · min¹;n = 8) and calf vascular resistance(39 ± 4 to 41 ± 4 units; n = 8). Heart rate (64 ± 3 to 66 ± 3 beats/min;P = 0.058) and mean arterial pressure(90 ± 3 to 93 ± 3; P < 0.05)increased slightly during head rotation. Additional neck flexionstudies were performed with subjects lying on their side(n = 5). MSNA, heart rate, and meanarterial pressure were unchanged during this maneuver, which also doesnot engage the vestibular system. HDNF was tested in 9 of the 13 subjects. MSNA was significantly increased by 79 ± 12% (P < 0.001) during HDNF. Thesefindings indicate that neck afferents activated by horizontal neckrotation or flexion in the absence of significant force development donot elicit changes in MSNA. These findings support the concept thatHDNF increases MSNA by the activation of the vestibular system.

     

Effect of acute head-down tilt on skeletal muscle cross-sectional area and proton transverse relaxation time

Conley, Michael S., Jeanne M. Foley, Lori L. Ploutz-Snyder,Ronald A. Meyer, and Gary A. Dudley. Effect of acute head-down tilt on skeletal muscle cross-sectional area and proton transverse relaxation time. J. Appl. Physiol.81(4): 1572-1577, 1996.This study investigated changes inskeletal muscle cross-sectional area (CSA) evoked by fluid shifts thataccompany short-term 6° head-down tilt (HDT) or horizontal bedrest, the time course of the resolution of these changes afterresumption of upright posture, and the effect of altered muscle CSA, inthe absence of increased contractile activity, on proton transverserelaxation time (T₂). Averagemuscle CSA and T₂ were determinedby standard spin-echo magnetic resonance imaging. Analyses wereperformed on contiguous transaxial images of the neck and calf. After aday of normal activity, 24 h of HDT increased neck muscle CSA 19 ± 4 (SE)% (P < 0.05) whilecalf muscle CSA decreased 14 ± 3%(P < 0.05). The horizontal posture(12 h) induced about one-half of these responses: an 11 ± 2%(P < 0.05) increase in neck muscleCSA and an 8 ± 2% decrease (P < 0.05) in the calf. Within 2 h after resumption of upright posture, neckand calf muscle CSA returned to within 0.5% (P > 0.05) of the values assessedafter a day of normal activity, with most of the change occurringwithin the first 30 min. No further change in muscle CSA was observedthrough 6 h of upright posture. Despite these large alterations inmuscle CSA, T₂ was not altered bymore than 1.1 ± 0.6% (P > 0.05)and did not relate to muscle size. These results suggest that posturalmanipulations and subsequent fluid shifts modeling microgravity elicitmarked changes in muscle size. Because these responses were notassociated with alterations in muscleT₂, it does not appear that simple movement of water into muscle can explain the contrast shift observed after exercise.

     

H2O2 increases sheep tracheal blood flow, permeability, and vascular response to luminal capsaicin

Wells, U. M., S. Duneclift, and J. G. Widdicombe.H₂O₂increases sheep tracheal blood flow, permeability, and vascular response to luminal capsaicin. J. Appl.Physiol. 82(2): 621-631, 1997.Exogenous hydrogenperoxide(H₂O₂)causes airway epithelial damage in vitro. We have studied the effectsof luminalH₂O₂in the sheep trachea in vivo on tracheal permeability tolow-molecular-weight hydrophilic (technetium-99m-labeleddiethylenetriamine pentaacetic acid;^99mTc-DTPA) and lipophilic([¹⁴C]antipyrine;[¹⁴C]AP) tracers andon the tracheal vascular response to luminal capsaicin, whichstimulates afferent nerve endings. A tracheal artery was perfused, andtracheal venous blood was collected. H₂O₂exposure (10 mM) reduced tracheal potential difference(42.0 ± 6.4 mV) to zero. It increased arterial andvenous flows (56.7 ± 6.1 and 57.3 ± 10.0%,respectively; n = 5, P < 0.01, paired t-test) but not tracheal lymph flow(unstimulated flow 5.0 ± 1.2 µl ^· min^{1 ·} cm¹,n = 4). DuringH₂O₂exposure, permeability to ^99mTc-DTPA increased from2.6 to 89.7 × 10⁷ cm/s(n = 5, P < 0.05), whereas permeability to[¹⁴C]AP (3,312.6 × 10⁷ cm/s,n = 4) was not altered significantly(2,565 × 10⁷cm/s). Luminal capsaicin (10 µM) increased tracheal blood flow (10.1 ± 4.1%, n = 5)and decreased venous ^99mTc-DTPAconcentration (19.7 ± 4.0, P < 0.01), and these effects weresignificantly greater after epithelial damage (28.1 ± 6.0 and45.7 ± 4.3%, respectively,P < 0.05, unpairedt-test). Thus H₂O₂increases the penetration of a hydrophilic tracer into tracheal bloodand lymph but has less effect on a lipophilic tracer. It also enhancesthe effects of luminal capsaicin on blood flow and tracer uptake.

     

Neuromuscular factors contributing to in vivo eccentric moment generation

Webber, Sandra, and Dean Kriellaars. Neuromuscularfactors contributing to in vivo eccentric moment generation.J. Appl. Physiol. 83(1): 40-45, 1997.Muscle series elasticity and its contribution to eccentricmoment generation was examined in humans. While subjects [male,n = 30; age 26.3 ± 4.8 (SD) yr; body mass 78.8 ± 13.1 kg] performed an isometric contractionof the knee extensors at 60° of knee flexion, a quick stretch was imposed with a 12°-step displacement at 100°/s. The test wasperformed at 10 isometric activation levels ranging from 1.7 to 95.2%of maximal voluntary contraction (MVC). A strong linear relationship was observed between the peak imposed eccentric moment derived fromquick stretch and the isometric activation level(y = 1.44x + 7.08; r = 0.99). This increase in theeccentric moment is consistent with an actomyosin-dependent elasticitylocated in series with the contractile element of muscle. Byextrapolating the linear relationship to 100% MVC, the predictedmaximum eccentric moment was found to be 151% MVC, consistent with invitro data. A maximal voluntary, knee extensor strength test was alsoperformed (5-95°, 3 repetitions, ±50, 100, 150, 200, and250°/s). The predicted maximum eccentric moment was 206% of theangle- and velocity-matched, maximal voluntary eccentric moments. Thiswas attributed to a potent neural regulatory mechanism that limits therecruitment and/or discharge of motor units during maximalvoluntary eccentric contractions.

     

Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz,R. L. Smith, J. L. Robotham, and C. P. O'Donnell. Systemic andpulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5):1671-1680, 1997.We examined the hemodynamic responses to normalbreathing and induced upper airway obstructions during sleep in acanine model of obstructive sleep apnea. During normal breathing,cardiac output decreased (12.9 ± 3.5%,P < 0.025) from wakefulness tonon-rapid-eye-movement sleep (NREM) but did not change from NREM torapid-eye-movement (REM) sleep. There was a decrease(P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures fromwakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg,P < 0.025), but not pulmonary,arterial pressures decreased from NREM to REM sleep. During repetitiveairway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiacoutput (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased(P < 0.05), without a change instroke volume, compared with normal breathing during NREM sleep. Duringsingle obstructive events, left (7.8 ± 3.0%,P < 0.05) and right (7.1 ± 0.7%, P < 0.01)ventricular outputs decreased during the apneic period. However, left(20.7 ± 1.6%, P < 0.01) andright (24.0 ± 4.2%, P < 0.05)ventricular outputs increased in the postapneic period because of anincrease in heart rate. Thus 1) thesystemic, but not the pulmonary, circulation vasodilates during REMsleep with normal breathing; 2)heart rate, rather than stroke volume, is the dominant factormodulating ventricular output in response to apnea; and3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.

     

Effect of neuropeptide Y on hemodynamics of the rabbit lung

Lang, Sally A., and Michael B. Maron.Effect of neuropeptide Y on hemodynamics of the rabbit lung.J. Appl. Physiol. 84(2): 618-623, 1998.We evaluated the effect of neuropeptide Y (NPY) on thehemodynamics of the isolated rabbit lung perfused at constant flow andoutflow pressure. Doses of10⁸ and10 ⁷ M NPY increasedpulmonary arterial pressure (Ppa) from 11.5 ± 1.0 (SE) mmHg to,respectively, 16.4 ± 1.5 and 26.0 ± 3.8 mmHg (P < 0.05, n = 5 mmHg lungs), with 78 ± 4%of the increase at 10⁷ Mresulting from an increased arterial resistance. At the latter dose,pulmonary capillary pressure increased from 5.8 ± 0.9 to 9.4 ± 1.0 mmHg (P < 0.05). Whenadministered in the presence of norepinephrine,10⁸ and10⁷ M NPY(n = 6) produced extreme increases inPpa to 66.1 ± 20.5 and 114.7 ± 25.5 mmHg, respectively, thatwere due primarily to an increased arterial resistance. To determinethe significance of circulating NPY as a pulmonary vasoactive agent, wemeasured plasma NPY-like immunoreactivity in anesthetized rabbits after massively activating the sympathetic nervous system with veratrine. NPY-like immunoreactivity increased from 74 ± 10 to 111 ± 10 (SE) pM (P < 0.05). Thus,although NPY is a potent vasoconstrictor in the rabbit lung, it is notlikely that plasma NPY concentrations rise sufficiently, even aftermassive sympathetic nervous system activation, to produce pulmonaryvasoconstriction in the intact rabbit.

     

Passive sensitization of human airways induces myogenic contractile responses in vitro

Mitchell, R. W., K. F. Rabe, H. Magnussen, and A. R. Leff.Passive sensitization of human airways induces myogenic contractile responses in vitro. J. Appl.Physiol. 83(4): 1276-1281, 1997.We assessedeffects of passive sensitization on human bronchial smooth muscle (BSM)response to mechanical stretching in vitro. Bronchial rings were sham(control) or passively sensitized overnight by using sera from donorsdemonstrating sensitivity to Dermatophagoides farinae and having immunoglobulin E (IgE)concentrations of 2,600 ± 200 U/ml. Tissues were fixedisometrically to force transducers to measure responses to electricalfield stimulation (EFS) and quick stretch (QS). The myogenic responseto QS was normalized to the maximal response to EFS (%EFS). Themyogenic response of sensitized BSM was 47.9 ± 10.9 %EFS to a QSof ~6.5% optimal length (L_o);sham-sensitized tissues had a myogenic response of 13.5 ± 6.4 %EFS(P = 0.012 vs. passively sensitized).A QS of ~13% L_o in sensitizedBSM caused a response of 82.8 ± 20.9 %EFS; sham-sensitized tissuesdeveloped a response of 38.2 ± 17.3 %EFS(P = 0.004). BSM incubated with serumfrom nonallergic donors did not demonstrate increased QS response (4.6 ± 1.4 %EFS, P = not significantvs. tissue exposed to atopic sera). However, tissues incubated in serafrom nonatopic donors supplemented with hapten-specific chimeric IgE(JW8) demonstrated augmented myogenic response to QS of ~6.5% L_o (21.9 ± 6.2 %EFS, P = 0.027 vs. nonatopicsera alone). We demonstrate that passive sensitization of human BSMpreparations causes induction and augmentation of myogenic contractionsto QS; this hyperresponsiveness corresponds to the IgE concentration insensitizing sera.