Chest wall mechanics in sustained microgravity

We assessed theeffects of sustained weightlessness on chest wall mechanics in fiveastronauts who were studied before, during, and after the 10-daySpacelab D-2 mission (n = 3)and the 180-day Euromir-95 mission (n = 2). We measured flow and pressure at the mouth and rib cage andabdominal volumes during resting breathing and during a relaxationmaneuver from midinspiratory capacity to functional residual capacity.Microgravity produced marked and consistent changes () in thecontribution of the abdomen to tidal volume [Vab/(Vab + Vrc), where Vab is abdominal volume and Vrc is rib cagevolume], which increased from 30.7 ± 3.5 (SE)% at1 G head-to-foot acceleration to 58.3 ± 5.7% at 0 G head-to-foot acceleration (P < 0.005). Values ofVab/(Vab + Vrc) did not change significantly during the 180 days of the Euromir mission, but in the two subjects Vab/(Vab + Vrc) was greater on postflight day1 than on subsequent postflight days or preflight. Inthe two subjects who produced satisfactory relaxation maneuvers, the slope of the Konno-Mead plot decreased in microgravity; this decrease was entirely accounted for by an increase in abdominal compliance because rib cage compliance did not change. These alterations aresimilar to those previously reported during short periods ofweightlessness inside aircrafts flying parabolic trajectories. They arealso qualitatively similar to those observed on going from upright tosupine posture; however, in contrast to microgravity, such posturalchange reduces rib cage compliance.

     

Association of chest wall motion and tidal volume responses during CO2 rebreathing

Yan, Sheng, Pawel Sliwinski, and Peter T. Macklem.Association of chest wall motion and tidal volume responses during CO₂ rebreathing.J. Appl. Physiol. 81(4):1528-1534, 1996.The purpose of this study is to investigate theeffect of chest wall configuration at end expiration on tidal volume(VT) response duringCO₂ rebreathing. In a group of 11 healthy male subjects, the changes in end-expiratory andend-inspiratory volume of the rib cage (Vrc,E andVrc,I, respectively) and abdomen (Vab,E and Vab,I, respectively) measured by linearizedmagnetometers were expressed as a function of end-tidalPCO₂(PET_CO2). The changes inend-expiratory and end-inspiratory volumes of the chest wall(Vcw,E and Vcw,I,respectively) were calculated as the sum of the respectiverib cage and abdominal volumes. The magnetometer coils were placed atthe level of the nipples and 1-2 cm above the umbilicus andcalibrated during quiet breathing against theVT measured from apneumotachograph. TheVrc,E/PET_CO2 slope was quite variable among subjects. It was significantly positive (P < 0.05) in fivesubjects, significantly negative in four subjects(P < 0.05), and not different fromzero in the remaining two subjects. TheVab,E/PET_CO2slope was significantly negative in all subjects(P < 0.05) with a much smallerintersubject variation, probably suggesting a relatively more uniformrecruitment of abdominal expiratory muscles and a variable recruitmentof rib cage muscles during CO₂rebreathing in different subjects. As a group, the meanVrc,E/PET_CO2,Vab,E/PET_CO2, andVcw,E/PET_CO2slopes were 0.010 ± 0.034, 0.030 ± 0.007, and0.020 ± 0.032 l / Torr, respectively;only theVab,E/PET_CO2 slope was significantly different from zero. More interestingly, theindividualVT/PET_CO2slope was negatively associated with theVrc,E/PET_CO2(r = 0.68,P = 0.021) and Vcw,E/PET_CO2slopes (r = 0.63,P = 0.037) but was not associated withtheVab,E/PET_CO2slope (r = 0.40, P = 0.223). There was no correlation oftheVrc,E/PET_CO2 andVcw,E/PET_CO2slopes with age, body size, forced expiratory volume in 1 s, orexpiratory time. The groupVab,I/PET_CO2 slope (0.004 ± 0.014 l / Torr) was not significantlydifferent from zero despite theVT nearly being tripled at theend of CO₂ rebreathing. Inconclusion, the individual VTresponse to CO₂, althoughindependent of Vab,E, is a function ofVrc,E to the extent that as theVrc,E/PET_CO2slope increases (more positive) among subjects, theVT response toCO₂ decreases. These results maybe explained on the basis of the respiratory muscle actions andinteractions on the rib cage.

     

Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects

Assisted ventilation with pressure support (PSV)or proportional assist (PAV) ventilation has the potential to produceperiodic breathing (PB) during sleep. We hypothesized that PB willdevelop when PSV level exceeds the product of spontaneous tidal volume (VT) and elastance(VT_sp · E)but that the actual level at which PB will develop[PSV(PB)] will be influenced by thePCO₂ (difference between eupneicPCO₂ andCO₂ apneic threshold) and by RR[response of respiratory rate (RR) to PSV]. We also wishedto determine the PAV level at which PB develops to assess inherentventilatory stability in normal subjects. Twelve normal subjectsunderwent polysomnography while connected to a PSV/PAV ventilatorprototype. Level of assist with either mode was increased in smallsteps (2-5 min each) until PB developed or the subject awakened.End-tidal PCO₂,VT, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated byrespiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from[(Paw + Pmus)/Pmus], where Paw is peak Paw  continuous positive airway pressure. PB with central apneas developedin 11 of 12 subjects on PSV. PCO₂ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small andbidirectional (+1.1 to 3.5min¹). With use ofstepwise regression, PSV(PB) was significantly correlated withVT_sp(P = 0.001), E(P = 0.00009),PCO₂ (P = 0.007), and RR(P = 0.006). The final regressionmodel was as follows: PSV(PB) = 11.1 VT_sp + 0.3E  0.4 PCO₂  0.34 RR  3.4 (r = 0.98). PBdeveloped in five subjects on PAV at amplification factors of1.5-3.4. It failed to occur in seven subjects, despite PAF of upto 7.6. We conclude that 1) aPCO₂ apneic threshold exists duringsleep at 1.5-5.8 Torr below eupneicPCO₂,2) the development of PB during PSVis entirely predictable during sleep, and3) the inherent susceptibility to PBvaries considerably among normal subjects.

     

TNF-alpha in smoke inhalation lung injury

Hales, Charles A., T. H. Elsasser, Peter Ocampo, and OlgaEfimova. TNF- in smoke inhalation lung injury.J. Appl. Physiol. 82(5):1433-1437, 1997.Adult respiratory distress syndrome is a majorcause of morbidity in fire victims. Tumor necrosis factor- (TNF-)is edematogenic and has been associated with the etiology of otherforms of adult respiratory distress syndrome. In the sheep lymphfistula model, we measured TNF- after 48 (n = 7) or 128 (n = 3) breaths of cotton smoke andcompared this with sham controls (n = 5) or controls in which left atrial pressure was elevated to 20 mmHg(n = 5) to increase lymph flow in the absence of inflammation. Smoke induced a rise in lymph flow and pulmonary arterial pressure with either no fall in lymph-to-plasma protein ratio (128 breaths) or a modest fall in lymph-to-plasma proteinratio (48 breaths), consistent with a change in microvascular permeability as well as a rise in microvascular pressure.Lymph concentration of TNF- fell in both groups, although lymph flux (concentration × flow) transiently rose in both. In neither case did TNF- flux exceed that induced by left atrial pressure elevation. TNF- was detectable in only one out of five sheep in alveolar lavage. Thus, by utilizing a sensitive and specific radioimmunoassay, we were unable to demonstrate a role for TNF- in smoke-induced microvascular lung injury in sheep.

     

Protein kinase C modulation of ventilatory response to hypoxia in nucleus tractus solitarii of conscious rats

This study aimedto determine the role of protein kinase C (PKC) in signal transductionmechanisms underlying ventilatory regulation in the nucleus tractussolitarii (NTS). Microinjection of phorbol 12-myristate 13-acetate intothe commissural NTS of nine chronically instrumented, unrestrained ratselicited significant cardiorespiratory enhancements that lasted for atleast 4 h, whereas administration of vehicle(n = 15) or the inactive phorbol ester 4-phorbol 12,13-didecanoate (n = 7)did not elicit minute ventilation (E)changes. Peak hypoxic Eresponses (10% O₂-balanceN₂) were measured in 19 additional animals after NTS microinjection of bisindolylmaleimide(BIM) I, a selective PKC inhibitor (n = 12), BIM V (inactive analog; n = 7),or vehicle (Con; n = 19). In Con,E increased from 139 ± 9 to 285 ± 26 ml/min in room air and hypoxia, respectively, and similarresponses occurred after BIM V. BIM I did not affect room airE but markedly attenuated hypoxia-induced E increases (128 ± 12 to 167 ± 18 ml/min; P < 0.02 vs. Con and BIM V). When BIM I was microinjected into the cerebellum(n = 4), cortex(n = 4), or spinal cord(n = 4),E responses were similar to Con.Western blots of subcellular fractions of dorsocaudal brain stemlysates revealed translocation of PKC, , , , , and  isoenzymes during acute hypoxia, and enhanced overall PKC activity wasconfirmed in the particulate fraction of dorsocaudal brain stem lysatesharvested after acute hypoxia. These studies suggest that, in the adultrat, PKC activation in the NTS mediates essential components of theacute hypoxic ventilatory response.

     

Role of tachykinins in ozone-induced airway hyperresponsiveness to cigarette smoke in guinea pigs

Wu, Zhong-Xin, Robert F. Morton, and Lu-Yuan Lee. Roleof tachykinins in ozone-induced airway hyperresponsiveness to cigarettesmoke in guinea pigs. J. Appl.Physiol. 83(3): 958-965, 1997.Acute exposure to ozone(O₃) induces airwayhyperresponsiveness to various inhaled bronchoactive substances.Inhalation of cigarette smoke, a common inhaled irritant in humans, isknown to evoke a transient bronchoconstrictive effect. To examinewhether O₃ increases airwayresponsiveness to cigarette smoke, effects of smoke inhalationchallenge on total pulmonary resistance(RL) and dynamic lungcompliance (Cdyn) were compared before and after exposure toO₃ (1.5 ppm, 1 h) in anesthetizedguinea pigs. Before O₃ exposure,inhalation of two breaths of cigarette smoke (7 ml) at a lowconcentration (33%) induced a mild and reproduciblebronchoconstriction that slowly developed and reached its peak(RL = 67 ± 19%, Cdyn = 29 ± 6%) after a delay of >1 min. After exposure toO₃ the same cigarette smokeinhalation challenge evoked an intense bronchoconstriction thatoccurred more rapidly, reaching its peak(RL = 620 ± 224%, Cdyn = 35 ± 7%) within 20 s, and was sustained for >2min. By contrast, sham exposure to room air did not alter thebronchomotor response to cigarette smoke challenge. Pretreatment withCP-99994 and SR-48968, the selective antagonists of neurokinin type 1 and 2 receptors, respectively, completely blocked the enhancedresponses of RL and Cdyn tocigarette smoke challenge induced byO₃. These results show thatO₃ exposure induces airwayhyperresponsiveness to inhaled cigarette smoke and that the enhancedresponses result primarily from the bronchoconstrictive effect ofendogenous tachykinins.

     

Mechanisms of stimulation of vagal pulmonary C fibers by pulmonary air embolism in dogs

Chen, H. F., B. P. Lee, and Y. R. Kou. Mechanisms ofstimulation of vagal pulmonary C fibers by pulmonary air embolism indogs. J. Appl. Physiol. 82(3):765-771, 1997.We investigated the involvement of thecyclooxygenase metabolites and hydroxyl radical (^· OH) in thestimulation of vagal pulmonary C fibers (PCs) by pulmonary air embolism(PAE). Impulses were recorded from PCs in 51 anesthetized, open-chest,and artificially ventilated dogs. Fifty of 59 PCs were stimulated byinfusion of air into the right atrium (0.2 ml ^· kg^{1 ·} min¹for 10 min). As a group (n = 59), PCactivity increased from a baseline of 0.4 ± 0.1 to a peak of 1.7 ± 0.2 impulses/s during the period from 1 min before to 2 min afterthe termination of PAE induction. In PCs initially stimulated by PAEinduction, PAE was repeated after the intervening treatment (iv) withsaline (n = 9), ibuprofen (acyclooxygenase inhibitor; n = 11), ordimethylthiourea (a ^· OH scavenger;n = 12). The responses of PCs to PAEwere not altered by saline vehicle but were abolished by ibuprofen and significantly attenuated by dimethylthiourea. Although hyperinflation of the lungs reversed the PAE-induced bronchomotor responses, it didnot reverse the stimulation of PCs (n = 8). These results suggest that 1)cyclooxygenase products are necessary for the stimulation of PCs byPAE, whereas changes in lung mechanics are not, and2) the functional importance ofcyclooxygenase products may be mediated in part through the formationof ^· OH.

     

Chemo- and baroresponses differ in African-Americans and Caucasians in sleep

To determine sleep effects on baro- andventilatory responses to transient chemo- and barostimulation inAfrican-Americans and Caucasians, 26 nonobese normotensive youngsubjects (13 African-Americans and 13 Caucasians) were studied awakeand in non-rapid-eye movement (NREM) and rapid-eye-movement sleepduring induced transient hypoxemia (N₂), hypertension(phenylephrine, PE), and concomitant hypoxemia and hypertension(N₂ + PE). Arterial blood pressurewas recorded by plethysmographic volume clamp, minute ventilation bypneumotachograph, and arterial O₂saturation by pulse oximeter. For all subjects, chronotropicbaroresponse (pulse interval/systolic blood pressure, where  is change) increased with NREM sleep(P = 0.007). Baroresponse slope wasgreater in Caucasians than in African-Americans (ANOVA, P = 0.02). Hypoxemic ventilatoryresponse (minute ventilation/arterial O₂ saturation) was greater inAfrican-Americans than in Caucasians in NREM sleep(P = 0.01), as was hypoxemicattenuation of baroresponse (N₂ + PE, P = 0.03). These data suggestsleep-related differences in arterial chemo- and baroreceptor responsesin normal young African-Americans and Caucasians, which may haveimplications concerning development of systemic hypertension.

     

Dissociation between hysteresivity and tension in constricted tracheal and parenchymal strips

The object of this study was to investigatehow changes in the contractile state of smooth muscle would modifyoscillatory mechanics of tracheal muscle and lung parenchyma duringagonist challenge. Guinea pig tracheal and parenchymal lung strips were suspended in an organ bath. Measurements of length(L) and tension (T) were recordedduring sinusoidal oscillations under baseline conditions and afterchallenge with 1 mM ACh. Measurements were also obtained in stripspretreated with the calmodulin inhibitor calmidazolium (Cmz) orstaurosporine (Stauro), a protein kinase C inhibitor. Elastance (E) andresistance (R) were calculated by fitting changes in T,L, andL/tto the equation of motion. Hysteresivity () was obtained from thefollowing equation: = (R/E)2f,where f is frequency. Finally, maximalunloaded shortening velocity during electrical field stimulation wasmeasured in Cmz-pretreated and control tracheal strips. In trachealstrips, pretreatment with Cmz caused a significant decrease in the  response to ACh challenge and in maximal unloaded shortening velocitymeasured during electrical field stimulation; Stauro decreased the T,E, and R response to ACh. In parenchymal strips, Cmz decreased the  response, whereas Stauro had no effect. These results suggest thatmodifications in the contractile state of the smooth muscle arereflected in changes in the hysteretic behavior and that T and  maybe controlled independently. Second, inasmuch as changes in  weresimilar in parenchymal and tracheal strips, the contractile element isimplicated as the structure responsible for constriction-induced changes in the mechanical behavior of the lung periphery.

     

Interaction of cross-sectional area, driving pressure, and airflow of passive velopharynx

Isono, Shiroh, Thom R. Feroah, Eric A. Hajduk, Rollin Brant,William A. Whitelaw, and John E. Remmers. Interaction ofcross-sectional area, driving pressure, and airflow of passive velopharynx. J. Appl. Physiol. 83(3):851-859, 1997.Previous studies have shown that, when thepharyngeal muscles are relaxed, the velopharynx is a highly compliantsegment of the pharynx. Thus, under these circumstances,cross-sectional area of the velopharynx (A_VP), drivingpressure across the velopharynx (P), and inspiratory airflow(I) willbe mutually interdependent variables. The purpose of the presentinvestigation was to describe the interrelation among these threevariables during inspiration. We studied 15 sleeping patients withobstructive sleep apnea/hypopnea when the pharyngeal muscles wererendered hypotonic by applying continuous positive airway pressure tothe nasal airway.A_VP, determined by endoscopic imaging, was significantly greater at onset ofI limitationthan at minimum oropharyngeal pressure(P < 0.01). Snoring was neverobserved duringIlimitation. In a subgroup of six patients, values for P,I, andA_VP were obtainedat 0.1-s intervals at various levels of mask pressure. For these sixpatients, the mathematical expressionI = 0.657(A_VP/A_max) · P^0.332,where A_max ismaximal A_VP,described the relationship among the three variables(R² = 0.962) forflow-limited and non-flow-limited inspirations. The impedance of thepassive velopharynx, defined asP^0.33/,was inversely related toA_VP and increaseddramatically when A_VP was <0.3cm². In summary, we observed aprogressive decrease inA_VP during flow-limited inspiration in patients with obstructive sleep apnea. Thisconstriction of the velopharynx contributes to an increase invelopharyngeal impedance that, in turn, counterbalances the increase inP during flow limitation.

     

Reduced blood flow in abdominal viscera measured by Doppler ultrasound during one-legged knee extension

The redistributionof blood flow (BF) in the abdominal viscera during right-legged kneeextension-flexion exercise at very low intensity [peak heart rate(HR), 76 beats/min] was examined by using Doppler ultrasound.While sitting, subjects performed a right-legged knee extension-flexionexercise every 6 s for 20 min. BF was measured in the upper abdominalaorta (Ao), right common femoral artery (RCFA), and left common femoralartery (LCFA). Visceral BF(BF_Vis) was determined by theequation [BF_Ao  (BF_RCFA + BF_LCFA)]. A comparisonwith the change in BF (BF) preexercise showed a greater increase inBF_RCFA than inBF_Ao during exercise. Thisresulted in a reduction of BF_Visto 56% of its preexercise value or a decrease in flow by 1,147 ± 293 (±SE) ml/min at the peak workload. Oxygen consumptioncorrelated positively withBF_Ao, BF_RCFA, andBF_LCFA but inversely withBF_Vis during exercise andrecovery. Furthermore, BF_Vis (% of preexercise value) correlated inversely with both an increase in HR(r = 0.89), and percent peakoxygen consumption (r = 0.99).This study demonstrated that, even during very-low-intensity exercise(HR <90 beats/min), there was a significant shift in BF from theviscera to the exercising muscles.     

Endothelial cell dilatory pathways link flow and wall shear stress in an intact arteriolar network

Frame, Mary D. S., and Ingrid H. Sarelius. Endothelialcell dilatory pathways link flow and wall shear stress in an intactarteriolar network. J. Appl. Physiol.81(5): 2105-2114, 1996.Our purpose was to determine whether theendothelial cell-dependent dilatory pathways contribute to theregulation of flow distribution in an intact arteriolar network. Cellflow, wall shear stress (T),diameter, and bifurcation angle were determined for four sequentialbranches of a transverse arteriole in the superfused cremaster muscleof pentobaribtal sodium (Nembutal, 70 mg/kg)-anesthetized hamsters(n = 51). Control cell flow wassignificantly greater into upstream than into downstream branches[1,561 ± 315 vs. 971 ± 200 (SE) cells/s,n = 12]. Tissue exposure to 50 µMN-nitro-L-arginine + 50 µM indomethacin (L-NNA + Indo) produced arteriolar constriction of 14 ± 4% and decreasedflow into the transverse arteriole. More of the available cell flow wasdiverted to downstream branches, yet flow distribution remainedunequal. Control T was higherupstream than downstream (31.3 ± 6.8 vs. 9.8 ± 1.5 dyn/cm²).L-NNA + Indo decreasedT upstream and increasedT downstream to become equal inall branches, in contrast to flow. To determine whether constriction ingeneral induced the same changes, 5%O₂ (8 ± 4% constriction) or10⁹ M norepinephrine (NE;4 ± 3% constriction) was added to the tissue (n = 7). WithO₂, flow was redistributed tobecome equal into each branch. With NE, flow decreased progressivelymore into the first three branches. The changes in flow distributionwere thus predictable and dependent on the agonist. WithO₂ or NE, the spatial changes inflow were mirrored by spatial changes inT. Changes in diameter and incell flux were not related forL-NNA + Indo (r = 0.45),O₂(r = 0.07), or NE(r = 0.36). For all agonists, when thebifurcation angle increased, cell flow to the branch decreasedsignificantly, whereas if the angle decreased, flow was relativelypreserved; thus active changes in bifurcation angle may influence redcell distribution at arteriolar bifurcations. Thus, when theendothelial cell dilatory pathways were blocked, the changes in flowand in T were uncoupled; yet when they were intact, flowand T changed together.

     

Determinants of diastolic myocardial tissue Doppler velocities: influences of relaxation and preload

Myocardial tissueDoppler echocardiography (TDE) has been proposed as a tool for theassessment of diastolic function. Controversy exists regarding whetherTDE measurements are influenced by preload. In this study, leftventricular volume and high-fidelity pressures were obtained ineight closed-chest dogs during intermittent caval occlusion. The timeconstant of isovolumic ventricular relaxation () was alteredwith varying doses of dobutamine and esmolol. Peak early diastolicmyocardial (E_m) and transmitral (E)velocities were measured before and after preload reduction. Therelative effects of changes in preload and relaxation were determinedfor E_m and compared with their effects onE. The following results were observed: caval occlusionsignificantly decreased E (E = 16.4 ± 3.3 cm/s, 36.6 ± 13.7%, P < 0.01) andE_m (E_m = 1.3 ± 0.4 cm/s, 32.5 ± 26.1%, P < 0.01) underbaseline conditions. However, preload reduction was similar forE under all lusitropic conditions (P = notsignificant), but these effects on E_m decreasedwith worsening relaxation. At  < 50 ms, changes inE_m with preload reduction were significantlygreater (E_m = 2.8 ± 0.6 cm/s) than at  = 50-65 ms (E_m = 1.2 ± 0.2 cm/s) and at  >65 ms(E_m = 0.5 ± 0.1 cm/s,P < 0.05). We concluded that TDEE_m is preload dependent. However, this effectdecreases with worsening relaxation.

     

Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise

Barstow, Thomas J., Andrew M. Jones, Paul H. Nguyen, andRichard Casaburi. Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise.J. Appl. Physiol. 81(4):1642-1650, 1996.We tested the hypothesis that the amplitude ofthe additional slow component ofO₂ uptake(O₂) during heavy exerciseis correlated with the percentage of type II (fast-twitch) fibers inthe contracting muscles. Ten subjects performed transitions to a workrate calculated to require aO₂ equal to 50% betweenthe estimated lactate (Lac) threshold and maximalO₂ (50%).Nine subjects consented to a muscle biopsy of the vastus lateralis. Toenhance the influence of differences in fiber type among subjects,transitions were made while subjects were pedaling at 45, 60, 75, and90 rpm in different trials. Baseline O₂ was designed to besimilar at the different pedal rates by adjusting baseline work ratewhile the absolute increase in work rate above the baseline was thesame. The O₂ response after the onset of exercise was described by a three-exponential model. Therelative magnitude of the slow component at the end of 8-min exercisewas significantly negatively correlated with %type I fibers at everypedal rate (r = 0.64 to 0.83, P < 0.05-0.01). Furthermore,the gain of the fast component forO₂ (asml ^· min^{1 ·} W¹)was positively correlated with the %type I fibers across pedal rates(r = 0.69-0.83). Increase inpedal rate was associated with decreased relative stress of theexercise but did not affect the relationships between%fiber type and O₂parameters. The relative contribution of the slow component was alsosignificantly negatively correlated with maximalO₂(r = 0.65), whereas the gainfor the fast component was positively associated(r = 0.68-0.71 across rpm). Theamplitude of the slow component was significantly correlated with netend-exercise Lac at all four pedal rates(r = 0.64-0.84), but Lac was notcorrelated with %type I (P > 0.05).We conclude that fiber type distribution significantly affects both thefast and slow components ofO₂ during heavy exerciseand that fiber type and fitness may have both codependent andindependent influences on the metabolic and gas-exchange responses toheavy exercise.

     

Determination of production of nitric oxide by lower airways of humans---theory

Hyde, Richard W., Edgar J. Geigel, Albert J. Olszowka, JohnA. Krasney, Robert E. Forster II, Mark J. Utell, and Mark W. Frampton.Determination of production of nitric oxide by the lower airwaysof humanstheory. J. Appl. Physiol.82(4): 1290-1296, 1997.Exercise and inflammatory lung disorderssuch as asthma and acute lung injury increase exhaled nitric oxide(NO). This finding is interpreted as a rise in production of NO by thelungs (NO)but fails to take into account the diffusing capacity for NO(DNO) that carries NO into thepulmonary capillary blood. We have derived equations to measureNO from thefollowing rates, which determine NO tension in the lungs(PL) at any moment from 1) production(NO);2) diffusion, whereDNO(PL) = rate of removal by lung capillary blood; and3) ventilation, whereA(PL)/(PB  47) = the rate of NO removal by alveolar ventilation(A) and PB is barometric pressure. During open-circuit breathingwhen PL is not in equilibrium,d/dtPL[V_L/(PB  47)] (where V_L is volumeof NO in the lower airways) = NO  DNO(PL)  A(PL)/(PB  47). When PL reaches asteady state so that d/dt = 0 andA iseliminated by rebreathing or breath holding, then PL = NO/DNO.PL can be interpreted as NOproduction per unit of DNO. Thisequation predicts that diseases that diminishDNO but do not alterNO willincrease expired NO levels. These equations permit precise measurementsof NO thatcan be applied to determining factors controlling NO production by thelungs.

     

Dynamic resistance exercise and resting blood pressure in adults: a meta-analysis

George, Kelley. Dynamic resistance exercise and restingblood pressure in adults: a meta-analysis. J. Appl.Physiol. 82(5): 1559-1565, 1997.With the use ofthe meta-analytic approach, the purpose of this study was to examinethe effects of dynamic resistance exercise, i.e., weight training, onresting systolic and diastolic blood pressure in adults. A total ofnine studies consisting of 259 subjects (144 exercise, 115 control) and18 groups (9 exercise, 9 control) were included in this analysis. Withthe use of the bootstrap technique (10,000 samples), significant treatment effect(₃)reductions were found across all designs and categories for bothsystolic and diastolic blood pressure [systolic, mean ± SD = 4.55 ± 1.75 mmHg, 95% confidence interval (CI) = 1.56 to 8.56; diastolic, mean ± SD = 3.79 + 1.12 mmHg, 95% confidence interval CI = 1.89 to6.33]. ₃ changescorresponded with relative decreases of ~3 and 4% in restingsystolic and diastolic blood pressure, respectively. Inconclusion, meta-analytic review of included studies suggests thatdynamic resistance exercise reduces resting systolic and diastolicblood pressure in adults. However, it is premature to form strongconclusions regarding the effects of dynamic resistance exercise onresting blood pressure. A need exists for additional, well-designedstudies on this topic before a recommendation can be made regarding theefficacy of dynamic resistance exercise as a nonpharmacological therapyfor reducing resting blood pressure in adults, especially inhypertensive adults.

     

Effect of cardiogenic and noncardiogenic pulmonary edema on histamine responsiveness in sheep

We compared the effects of cardiogenic pulmonaryedema, brief pulmonary vascular congestion without frank edema, andnoncardiogenic pulmonary edema on responsiveness to inhaled histaminein chronically instrumented awake sheep. Histamine responsiveness wasmeasured before and after 1)cardiogenic pulmonary edema induced by raising left atrial pressure to35 cmH₂O(Pla) for 3.5 h by partial obstruction of flowacross the mitral valve, 2) briefcardiogenic congestion via Pla for 0.5 h,3) noncardiogenic pulmonary edemainduced by 25 mg/kg intravenous perilla ketone (PK), and4) 3.5 h of monitoring withoutPla or PK (controls). Treatment for 3.5 h with Pla(n = 9) and PK(n = 11) each significantly lessenedthe histamine dose required to cause a fall to 65% of baseline dynamiclung compliance (ED₆₅Cdyn), i.e.,increased responsiveness. Sheep treated for 0.5 h with Pla(n = 7) and controls(n = 5) showed no significant changein ED₆₅Cdyn. Intravenous atropine(0.1 mg/kg) before the second histamine challenge altered neither thereduction of ED₆₅Cdyn inPla (n = 8) and PK(n = 9) sheep nor theED₆₅Cdyn level of controls(n = 9). These data imply that thelocal effects of edema, rather than bronchial vascular hemodynamics,cholinergic reflexes, and permeability changes, are germane to lunghyperresponsiveness during pulmonary edema in sheep.

     

Effects of dopamine and domperidone on ventilatory sensitivity to hypoxia after 8h of isocapnic hypoxia

Acclimatization to altitude involves an increase in the acutehypoxic ventilatory response (AHVR). Because low-dose dopamine decreases AHVR and domperidone increases AHVR, the increase in AHVR ataltitude may be generated by a decrease in peripheral dopaminergicactivity. The AHVR of nine subjects was determined with and without aprior period of 8 h of isocapnic hypoxia under each of threepharmacological conditions: 1)control, with no drug administered;2) dopamine (3 µg · min¹ · kg¹);and 3) domperidone (Motilin, 40 mg).AHVR increased after hypoxia (P  0.001). Dopaminedecreased (P  0.01), and domperidone increased (P  0.005) AHVR. The effect of both drugs on AHVR appearedlarger after hypoxia, an observation supported by a significantinteraction between prior hypoxia and drug in the analysis of variance(P  0.05). Although the increasedeffect of domperidone after hypoxia of 0.40 l · min¹ · %saturation¹[95% confidence interval (CI) 0.11 to 0.92 l · min¹ · %¹]did not reach significance, the lower limit for this confidence interval suggests that little of the increase in AHVR after sustained hypoxia was brought about by a decrease in peripheral dopaminergic inhibition.

     

Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of alpha 1- and alpha 2-adrenoceptor activation

Zschauer, A. O. A., M. W. Sielczak, D. A. S. Smith, and A. Wanner. Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of ₁-and ₂-adrenoceptor activation. J. Appl. Physiol. 82(6):1918-1925, 1997.The contractile effect of norepinephrine (NE) onisolated rabbit bronchial artery rings (150-300 µm in diameter)and the role of ₁- and₂-adrenoceptors (AR) on smoothmuscle and endothelium were studied. In intact arteries, NE increasedtension in a dose-dependent manner, and the sensitivity for NE wasfurther increased in the absence of endothelium. In intact but not inendothelium-denuded arteries, the response to NE was increased in thepresence of both indomethacin (Indo; cyclooxygenase inhibitor) andN^G-nitro-L-argininemethyl ester [L-NAME;nitric oxide (NO) synthase inhibitor], indicating that twoendothelium-derived factors, NO and a prostanoid, modulate theNE-induced contraction. The₁-AR antagonist prazosinshifted the NE dose-response curve to the right, and phenylephrine(₁-AR agonist) induced adose-dependent contraction that was potentiated byL-NAME or removal of theendothelium. The sensitivity to NE was increased slightly by the₂-AR antagonists yohimbine andidazoxan, and this effect was abolished by Indo or removal of theendothelium. Similarly, contractions induced by UK-14304(₂-AR agonist) were potentiatedby Indo or removal of the endothelium. These results suggest thatNE-induced contraction is mediated through activation of₁- and₂-ARs on both smooth muscle andendothelium. Activation of the₁- and₂-ARs on the smooth musclecauses contraction, whereas activation of the endothelial ₁- and₂-ARs induces relaxationthrough release of NO (₁-ARs) and a prostanoid (₂-ARs).

     

Oxygen transport in conscious newborn dogs during hypoxic hypometabolism

We questioned whether the decrease inO₂ consumption(O₂) during hypoxia innewborns is a regulated response or reflects a limitation inO₂ availability. Experiments wereconducted on previously instrumented conscious newborn dogs.O₂ was measured at a warmambient temperature (30°C, n = 7)or in the cold (20°C, n = 6),while the animals breathed air or were sequentially exposed to 15 minof fractional inspired O₂(FI_O2): 21, 18, 15, 12, 10, 8, and 6%. In normoxia,O₂ averaged 15 ± 1 (SE)and 25 ± 1 ml · kg¹ · min¹in warm and cold conditions, respectively. In the warmcondition, hypometabolism (i.e., hypoxicO₂ < normoxicO₂) occurred at FI_O2 10%, whereas in thecold condition, hypometabolism occurred atFI_O2 12%. The sameresults were obtained in a separate group(n = 14) of noninstrumented puppies.For all levels of FI_O2 withhypometabolism, the relationships between measures ofO₂ availability (arterialO₂ saturation or content, venousPO₂ or saturation,x-axis) vs.O₂(y-axis) had lower slopes in warm than in coldconditions. Hence, O₂ during hypometabolism in the warm condition was not the maximal attainable for the level of oxygenation. The results do not support thepossibility that the hypoxic drop inO₂ in the newborn reflects a limitation in O₂availability. The results are compatible with the ideathat the phenomenon is one of "regulated conformism" tohypoxia.