XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism

Terada, Lance S., Brooks M. Hybertson, Kevin G. Connelly,David Weill, Dale Piermattei, and John E. Repine. XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism. J. Appl.Physiol. 82(3): 866-873, 1997.Circulatingxanthine oxidase (XO) can modify adhesive interactions betweenneutrophils and the vascular endothelium, although the mechanismsunderlying this effect are not clear. We found that treatment with XOof bovine pulmonary artery endothelial cells (EC), but not neutrophilsor plasma, increased adherence, suggesting that XO had its primaryeffect on EC. The mechanism by which XO increased neutrophil adherenceto EC involved binding of XO to EC and production ofH₂O₂.XO also increased platelet-activating factor production by EC by aH₂O₂-dependentmechanism. Similarly, the platelet-activating factor-receptorantagonist WEB-2086 completely blocked XO-mediated neutrophil ECadherence. In addition, neutrophil adherence was dependent on the₂-integrin Mac-1 (CD11b/CD18) but not on leukocyte functional antigen-1 (CD11a/CD18). Treatment of ECwith XO for 30 min did not alter intercellular adhesion molecule-1surface expression but increased expression of P-selectin and releaseof von Willibrand factor. Antibodies against P-selectin (CD62) did notaffect XO-mediated neutrophil adherence under static conditions butdecreased both rolling and firm adhesive interactions under conditionsof shear. We conclude that extracellular XO associates with theendothelium and promotes neutrophil-endothelial cell interactionsthrough dual intercellular adhesion molecule-1 and P-selectin ligation,by a mechanism that involves platelet-activating factor andH₂O₂as intermediates.

     

Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled beta -agonists

Carvalho, Paula, Shane R. Johnson, Nirmal B. Charan.Non-cAMP-mediated bronchial arterial vasodilation in response toinhaled -agonists. J. Appl.Physiol. 84(1): 215-221, 1998.We studied thedose-dependent effects of inhaled isoetharine HCl, a -adrenergicbronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow(br) in anesthetized sheep. Isoetharine resulted ina dose-dependent increase in br. With atotal dose of 17.5 mg, br increased from baselinevalues of 22 ± 3.4 (SE) to 60 ± 16 ml/min(P < 0.001), an effect independentof changes in cardiac output and systemic arterial pressure. To furtherstudy whether synthesis of endogenous nitric oxide (NO) affects-agonist-induced increases in br, weadministered isoetharine (20 mg) by inhalation before and after theNO-synthase inhibitorN-nitro-L-argininemethyl ester (L-NAME).Intravenous L-NAME (30 mg/kg) rapidly decreased br by ~80% of baseline,whereas L-NAME via inhalation(10 mg/kg) resulted in a delayed and smaller (~22%) decrease.Pretreatment with L-NAME viaboth routes of administration attenuated bronchial arterialvasodilation after subsequent challenge with isoetharine. We concludethat isoetharine via inhalation increases br in adose-dependent manner and that -agonist-induced relaxation ofvascular smooth muscle in the bronchial vasculature is partiallymediated via synthesis of NO.

     

Nitric oxide and beta -adrenergic agonist-induced bronchial arterial vasodilation

Charan, Nirmal B., Shane R. Johnson, S. Lakshminarayan,William H. Thompson, and Paula Carvalho. Nitric oxide and-adrenergic agonist-induced bronchial arterial vasodilation.J. Appl. Physiol. 82(2): 686-692, 1997.In anesthetized sheep, we measured bronchial blood flow(br) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) givenfor 5 min and 5 ml of aerosolized isoetharine (1.49 × 10² M concentration).NO and isoetharine increased br from 26.5 ± 6.5 to 39.1 (SE) ± 10.6 and 39.7 ± 10.7 ml/min,respectively (n = 5).Administration of NO immediately after isoetharine further increasedbr to 57.3 ± 15.1 ml/min. NO synthase inhibitorN-nitro-L-arginine methyl esterhydrochloride (L-NAME; 30 mg/kg, in 20 ml salinegiven iv) decreased br to 14.6 ± 2.6 ml/min. NO given three times alternately with isoetharine progressively increased br from 14.6 ± 2.6 to 74.3 ± 17.0 ml/min, suggesting that NO and isoetharine potentiatevasodilator effects of each other. In three other sheep, afterL-NAME, three sequential doses of isoetharine increased br from 10.2 ± 3.4 to11.5 ± 5.7, 11.7 ± 4.7, and 13.3 ± 5.7 ml/min,respectively, indicating that effects of isoetharine are predominantlymediated through synthesis of NO. When this was followed by threesequential administrations of NO, br increased by146, 172, and 185%, respectively. Thus in the bronchial circulationthere seems to be a close interaction between adenosine3,5-cyclic monophosphate- and guanosine3,5-cyclic monophosphate-mediated vasodilatation.

     

Bronchial vasodilatory response to ionic and nonionic contrast media

Baile, Elisabeth M., Lu Wang, Lorraine Verburgt, and PeterD. Paré. Bronchial vasodilatory response to ionic andnonionic contrast media. J. Appl.Physiol. 82(3): 841-845, 1997.It has recentlybeen shown that bronchial arterial injection of conventional contrastmedium causes a significant increase in bronchial blood flow(br) and that this response is partially attenuatedafter infusion ofN-nitro-L-arginine(L-NNA). However, the precisemechanism for this increase in br is unknown. Inthis study we examined the effect of bronchial arterial injection ofconventional ionic as well as nonionic contrast media. We measuredbr in nine anesthetized, ventilated, open-chestsheep. br was recorded before (baseline) and at thepeak response to injection of 0.5 ml of either 0.9% saline (control;isosmolar with plasma), Omnipaque 300 (iohexol; nonionic), Conray 66 (sodium iothalamate; ionic), or 50% dextrose (viscouscontrol).

     

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.

     

NO does not mediate inhibitory neural responses in sheep airway and bronchial vascular smooth muscle

Endogenous nitric oxide (NO) influences acetylcholine-inducedbronchovascular dilation in sheep and is a mediator of the airway smooth muscle inhibitory nonadrenergic, noncholinergic neural responsein several species. This study was designed to determine the importanceof NO as a neurally derived modulator of ovine airway and bronchialvascular smooth muscle. We measured the response of pulmonaryresistance (RL) and bronchialblood flow (br) to vagal stimulationin 14 anesthetized, ventilated, open-chest sheep duringthe following conditions: 1)control; 2) infusion of the -agonist phenylephrine to reduce baseline br bythe same amount as would be produced by infusion ofN-nitro-L-arginine(L-NNA), a NO synthaseinhibitor; 3) infusion ofL-NNA(10² M); and4) after administration of atropine(1.5 mg/kg). The results showed that vagal stimulation produced anincrease in RL andbr in periods 1, 2, and 3 (P < 0.01) that was not affected byL-NNA. Afteratropine was administered, there was no increase inbr or RL. Invitro experiments on trachealis smooth muscle contracted with carbachol showed no effect ofL-NNA on neural relaxation butshowed a complete blockade with propranolol(P < 0.01). In conclusion, thevagally induced airway smooth muscle contraction and bronchial vasculardilation are not influenced by NO, and the sheep's trachealis muscle,unlike that in several other species, does not have inhibitorynonadrenergic, noncholinergic innervation.

     

Role for anions in pulmonary endothelial permeability

Griffin, M. Pamela. Role for anions in pulmonaryendothelial permeability. J. Appl.Physiol. 83(2): 615-622, 1997.-Adrenergic stimulation reduces albumin permeation across pulmonary artery endothelial monolayers and induces changes in cell morphology that aremediated by Cl flux. Wetested the hypothesis that anion-mediated changes in endothelial cellsresult in changes in endothelial permeability. We measured permeationof radiolabeled albumin across bovine pulmonary arterial endothelialmonolayers when the extracellular anion was Cl,Br,I,F, acetate(Ac), gluconate(G), and propionate(Pr). Permeability toalbumin (P_albumin)was calculated before and after addition of 0.2 mM of thephosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), whichreduces permeability. InCl, theP_albumin was 3.05 ± 0.86 × 10⁶ cm/s andfell by 70% with the addition of IBMX. The initialP_albumin was lowest forPr andAc. InitialP_albumin was higher inBr,I,G, andF than inCl. A permeability ratiowas calculated to examine the IBMX effect. The greatest IBMX effect wasseen when Cl was theextracellular anion, and the order among halide anions wasCl > Br > I > F. Although the level ofextracellular Ca²⁺ concentration([Ca²⁺]_o)varied over a wide range in the anion solutions,[Ca²⁺]_odid not systematically affect endothelial permeability in this system.When Cl was theextracellular anion, varying[Ca²⁺]_ofrom 0.2 to 2.8 mM caused a change in initialP_albumin but no changein the IBMX effect. The anion channel blockers4-acetamido-4-isothiocyanotostilbene-2,2-disulfonic acid(0.25 mM) and anthracene-9-carboxylic acid (0.5 mM) significantly altered initialP_albumin and the IBMXeffect. The anion transport blockers bumetanide (0.2 mM) and furosemide(1 mM) had no such effects. We conclude that extracellular anionsinfluence bovine pulmonary arterial endothelial permeability and thatthe pharmacological profile fits better with the activity of anionchannels than with other anion transport processes.

     

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.

     

Changes in maximum oxygen uptake during prolonged training, overtraining, and detraining in horses

Tyler, Catherine M., Lorraine C. Golland, David L. Evans,David R. Hodgson, and Reuben J. Rose. Changes in maximum oxygenuptake during prolonged training, overtraining, and detraining inhorses. J. Appl. Physiol. 81(5):2244-2249, 1996.Thirteen standardbred horses were trained asfollows: phase 1 (endurance training, 7 wk),phase 2 (high-intensity training, 9 wk),phase 3 (overload training, 18 wk), andphase 4 (detraining, 12 wk). Inphase 3, the horses were divided intotwo groups: overload training (OLT) and control (C). The OLT groupexercised at greater intensities, frequencies, and durations than groupC. Overtraining occurred after 31 wk of training and was defined as asignificant decrease in treadmill run time in response to astandardized exercise test. In the OLT group, there was a significantdecrease in body weight (P < 0.05).From pretraining values of 117 ± 2 (SE)ml ^· kg^{1 ·} min¹,maximal O₂ uptake(O_{2 max}) increased by15% at the end of phase 1, and when signs of overtraining werefirst seen in the OLT group,O_{2 max} was 29%higher (151 ± 2 ml ^· kg^{1 ·} min¹in both C and OLT groups) than pretraining values. There was nosignificant reduction inO_{2 max} until after 6 wk detraining whenO_{2 max} was 137 ± 2 ml ^· kg^{1 ·} min¹.By 12 wk detraining, meanO_{2 max} was134 ± 2 ml ^· kg^{1 ·} min¹,still 15% above pretraining values. When overtraining developed, O_{2 max} was notdifferent between C and OLT groups, but maximal values forCO₂ production (147 vs. 159 ml ^· kg^{1 ·} min¹)and respiratory exchange ratio (1.04 vs. 1.11) were lower in the OLTgroup. Overtraining was not associated with a decrease inO_{2 max} and, afterprolonged training, decreases inO_{2 max} occurredslowly during detraining.

     

Greater rate of decline in maximal aerobic capacity with age in physically active vs. sedentary healthy women

Tanaka, Hirofumi, Christopher A. DeSouza, Pamela P. Jones,Edith T. Stevenson, Kevin P. Davy, and Douglas R. Seals. Greater rate of decline in maximal aerobic capacity with age in physically active vs. sedentary healthy women. J. Appl.Physiol. 83(6): 1947-1953, 1997.Using ameta-analytic approach, we recently reported that the rate of declinein maximal oxygen uptake(O_{2 max}) with age inhealthy women is greatest in the most physically active and smallest inthe least active when expressed in milliliters per kilogram per minuteper decade. We tested this hypothesis prospectively underwell-controlled laboratory conditions by studying 156 healthy, nonobesewomen (age 20-75 yr): 84 endurance-trained runners (ET) and 72 sedentary subjects (S). ET were matched across the age range forage-adjusted 10-km running performance. Body mass was positivelyrelated with age in S but not in ET. Fat-free mass was not differentwith age in ET or S. Maximal respiratory exchange ratio and rating ofperceived exertion were similar across age in ET and S, suggestingequivalent voluntary maximal efforts. There was a significant butmodest decline in running mileage, frequency, and speed with advancingage in ET.O_{2 max}(ml · kg¹ · min¹)was inversely related to age (P < 0.001) in ET (r = 0.82) and S(r = 0.71) and was higher atany age in ET. Consistent with our meta-analysic findings,the absolute rate of decline inO_{2 max} was greater inET (5.7ml · kg¹ · min¹ · decade¹)compared with S (3.2 ml · kg¹ · min¹ · decade¹;P < 0.01), but the relative (%)rate of decline was similar (9.7 vs 9.1%/decade; notsignificant). The greater absolute rate of decline inO_{2 max} in ET comparedwith S was not associated with a greater rate of decline in maximalheart rate (5.6 vs. 6.2beats · min¹ · decade¹),nor was it related to training factors. The present cross-sectional findings provide additional evidence that the absolute, but not therelative, rate of decline in maximal aerobic capacity with age may begreater in highly physically active women compared with theirsedentary healthy peers. This difference does not appear to be relatedto age-associated changes in maximal heart rate, bodycomposition, or training factors.

     

Effect of inhibition of nitric oxide synthesis on the diaphragmatic microvascular response to hypoxia

Ward, Michael E. Effect of inhibition of nitric oxidesynthesis on the diaphragmatic microvascular response to hypoxia. J. Appl. Physiol. 81(4):1633-1641, 1996.The purpose of this study was to determine theeffect of inhibition of nitric oxide (NO) release on the diaphragmaticmicrovascular responses to hypoxia. In -chloralose-anesthetizedmongrel dogs, the microcirculation of the vascularly isolated ex vivoleft hemidiaphragm was studied by intravital microscopy. The diaphragmwas pump perfused with blood diverted from the femoral artery through aseries of membrane oxygenators. The responses to supramaximalconcentrations of sodium nitroprusside, moderate hypoxia (phrenicvenous PO₂ 27 Torr), andsevere hypoxia (phrenic venous PO₂ 15 Torr) were recorded before and after an infusion ofN^G-nitro-L-arginine(L-NNA; 6 × 10⁴ M) into the phreniccirculation for 20 min. Under control conditions, diaphragmatic bloodflow was 12.4 ± 1.1 ml ^· min^{1 ·} 100 g¹. Diaphragmatic bloodflows recorded during moderate and severe hypoxia were 15.6 ± 1.2 and 24.3 ± 1.5 ml ^· min^{1 ·} 100 g¹, respectively(P < 0.05 for both compared withcontrol values). Treatment withL-NNA reduced diaphragmaticblood flow to 9.6 ± 0.8 ml ^· min^{1 ·} 100 g¹ under control conditions(P < 0.05) and caused arteriolarvasoconstriction to a degree that was dependent on vessel size (i.e.,larger vessels constricted more than smaller vessels).L-NNA eliminated the increase inblood flow during moderate hypoxia and inhibited arteriolar dilation byan amount that was related to vessel size (i.e., dilation of largervessels was inhibited more than that of smaller vessels). Inhibition ofNO synthesis had no effect on the increase in diaphragmatic blood flow(23.6 ± 1.9 ml ^· min^{1 ·} 100 g¹;P > 0.05 compared with that duringsevere hypoxia before treatment withL-NNA) or arteriolar diametersduring severe hypoxia. NO release plays a role in the diaphragmaticvascular response to hypoxia, but this role is limited to dilation oflarger arterioles during hypoxia of moderate severity.

     

Importance of the lactate anion in control of breathing

Hardarson, Thorir, Jon O. Skarphedinsson, and TorarinnSveinsson. Importance of the lactate anion in control ofbreathing. J. Appl. Physiol. 84(2):411-416, 1998.The purpose of this study was to examine theeffects of raising the arterialLa andK⁺ levels on minute ventilation(E) in rats. EitherLa or KCl solutions wereinfused in anesthetized spontaneously breathing Wistar rats to raisethe respective ion arterial concentration ([La] and[K⁺]) gradually tolevels similar to those observed during strenuous exercise.E, blood pressure, and heart rate wererecorded continuously, and arterial[La],[K⁺], pH, and bloodgases were repeatedly measured from blood samples. To prevent changesin pH during the Lainfusions, a solution of sodium lactate and lactic acid was used. Raising [La] to13.2 ± 0.6 (SE) mM induced a 47.0 ± 4.0% increase inE without any concomitant changes ineither pH or PCO₂. Raising[K⁺] to 7.8 ± 0.11 mM resulted in a 20.3 ± 5.28% increase inE without changes in pH. Thus ourresults show that Laitself, apart from lactic acidosis, may be important in increasing E during strenuous exercise, and weconfirm earlier results regarding the role of arterial[K⁺] in the control ofE during exercise.

     

Combined heart rate and activity improve estimates of oxygen consumption and carbon dioxide production rates

Moon, Jon K., and Nancy F. Butte. Combined heart rateand activity improve estimates of oxygen consumption and carbon dioxideproduction rates. J. Appl. Physiol.81(4): 1754-1761, 1996.Oxygen consumption(O₂) andcarbon dioxide production (CO₂) rates were measuredby electronically recording heart rate (HR) and physical activity (PA).Mean daily O₂ andCO₂ measurements by HR andPA were validated in adults (n = 10 women and 10 men) with room calorimeters. Thirteen linear and nonlinear functions of HR alone and HR combined with PA were tested as models of24-h O₂ andCO₂. Mean sleepO₂ andCO₂ were similar to basalmetabolic rates and were accurately estimated from HR alone[respective mean errors were 0.2 ± 0.8 (SD) and0.4 ± 0.6%]. The range of prediction errorsfor 24-h O₂ andCO₂ was smallestfor a model that used PA to assign HR for each minute to separateactive and inactive curves(O₂, 3.3 ± 3.5%; CO₂, 4.6 ± 3%). There were no significant correlations betweenO₂ orCO₂ errors and subject age,weight, fat mass, ratio of daily to basal energy expenditure rate, orfitness. O₂,CO₂, and energy expenditurerecorded for 3 free-living days were 5.6 ± 0.9 ml ^· min^{1 ·} kg¹,4.7 ± 0.8 ml ^· min^{1 ·} kg¹,and 7.8 ± 1.6 kJ/min, respectively. Combined HR and PA measured 24-h O₂ andCO₂ with a precisionsimilar to alternative methods.

     

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.

     

Age-related declines in maximal aerobic capacity in regularly exercising vs. sedentary women: a meta-analysis

Fitzgerald, Margaret D., Hirofumi Tanaka, Zung V. Tran, andDouglas R. Seals. Age-related declines in maximal aerobic capacityin regularly exercising vs. sedentary women: a meta-analysis. J. Appl. Physiol. 83(1): 160-165, 1997.Our purpose was to determine the relationship between habitualaerobic exercise status and the rate of decline in maximal aerobiccapacity across the adult age range in women. A meta-analytic approachwas used in which mean maximal oxygen consumption(O_{2 max}) values fromfemale subject groups (ages 18-89 yr) were obtained from thepublished literature. A total of 239 subject groups from 109 studiesinvolving 4,884 subjects met the inclusion criteria and werearbitrarily separated into sedentary (groups = 107; subjects = 2,256),active (groups = 69; subjects = 1,717), and endurance-trained (groups = 63; subjects = 911) populations.O_{2 max} averaged 29.7 ± 7.8, 38.7 ± 9.2, and 52.0 ± 10.5 ml · kg¹ · min¹,respectively, and was inversely related to age within each population (r = 0.82 to 0.87, allP < 0.0001). The rate of decline inO_{2 max} withincreasing subject group age was lowest in sedentary women (3.5ml · kg¹ · min¹· decade¹), greater inactive women (4.4ml · kg¹ · min¹· decade¹), andgreatest in endurance-trained women (6.2ml · kg¹ · min¹ · decade¹)(all P < 0.001 vs. each other). Whenexpressed as percent decrease from mean levels at age ~25 yr, therates of decline inO_{2 max} were similarin the three populations (10.0 to 10.9%/decade). Therewas no obvious relationship between aerobic exercise status and therate of decline in maximal heart rate with age. The results of thiscross-sectional study support the hypothesis that, in contrast to theprevailing view, the rate of decline in maximal aerobic capacity withage is greater, not smaller, in endurance-trained vs. sedentary women.The greater rate of decline inO_{2 max} in endurance-trained populations may be related to their higher values asyoung adults (baseline effect) and/or to greater age-related reductions in exercise volume; however, it does not appear to berelated to a greater rate of decline in maximal heart rate with age.

     

Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension

Adrie, Christophe, Fumito Ichinose, AlexandraHolzmann, Larry Keefer, William E. Hurford, and Warren M. Zapol. Pulmonary vasodilation by nitric oxide gas and prodrugaerosols in acute pulmonary hypertension. J. Appl. Physiol. 84(2): 435-441, 1998.Sodium 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate{DEA/NO;Et₂N[N(O)NO]Na} is a compound that spontaneously generates nitric oxide (NO). Becauseof its short half-life (2.1 min), we hypothesized that inhaling DEA/NOaerosol would selectively dilate the pulmonary circulation withoutdecreasing systemic arterial pressure. We compared the pulmonaryselectivity of this new NO donor with two other reference drugs:inhaled NO and inhaled sodium nitroprusside (SNP). In seven awake sheepwith pulmonary hypertension induced by the infusion of U-46619, wecompared the hemodynamic effects of DEA/NO with those of incrementaldoses of inhaled NO gas. In seven additional awake sheep, we examinedthe hemodynamic effects of incremental doses of inhaled nitroprusside(i.e., SNP). Inhaled NO gas selectively dilated the pulmonaryvasculature. Inhaled DEA/NO produced nonselective vasodilation; bothsystemic vascular resistance (SVR) and pulmonary vascular resistance(PVR) were reduced. Inhaled SNP selectively dilated the pulmonarycirculation at low concentrations(10² M), inducing adecrease of PVR of up to 42% without any significant decrease of SVR(5%), but nonselectively dilated the systemic circulation atlarger doses (>10² M). Inconclusion, despite its short half-life, DEA/NO is not a selectivepulmonary vasodilator compared with inhaled NO. Inhaled SNP appears tobe selective to the pulmonary circulation at low doses but not athigher levels.

     

Effects of nitric oxide on blood flow distribution and O2 extraction capabilities during endotoxic shock

Zhang, Haibo, Peter Rogiers, Nadia Smail, Ana Cabral,Jean-Charles Preiser, Marie-Odile Peny, and Jean-Louis Vincent.Effects of nitric oxide on blood flow distribution andO₂ extraction capabilities duringendotoxic shock. J. Appl. Physiol.83(4): 1164-1173, 1997.The effects of the nitric oxide (NO)synthase inhibitorN^G-monomethyl-L-arginine(L-NMMA) and the NO donor3-morpholinosydnonimine (SIN-1) were tested in 18 endotoxic dogs. L-NMMA infusion(10 mg · kg¹ · h¹)increased arterial and pulmonary artery pressures and systemic andpulmonary vascular resistances but decreased cardiac index, leftventricular stroke work index, and blood flow to the hepatic, portal,mesenteric, and renal beds. SIN-1 infusion (2 µg · kg¹ · min¹)increased cardiac index; left ventricular stroke work index; andhepatic, portal, and mesenteric blood flow. It did not significantly influence arterial and pulmonary artery pressures but decreased renalblood flow. The critical O₂delivery was similar in the L-NMMA group and in the controlgroup (13.3 ± 1.6 vs. 12.8 ± 3.3 ml · kg¹ · min¹)but lower in the SIN-1 group (9.1 ± 1.8 ml · kg¹ · min¹,both P < 0.05). The criticalO₂ extraction ratio was alsohigher in the SIN-1 group than in the other groups (58.7 ± 10.6 vs.42.2 ± 7.6% in controls, P < 0.05; 43.0 ± 15.5% inL-NMMA group,P = not significant). We conclude thatNO is not implicated in the alterations inO₂ extraction capabilitiesobserved early after endotoxin administration.

     

Vascular tree structure affects lung blood flow heterogeneity simulated in three dimensions

Parker, James C., Chris B. Cave, Jeffrey L. Ardell, CharlesR. Hamm, and Susan G. Williams. Vascular treestructure affects lung blood flow heterogeneity simulated in threedimensions. J. Appl. Physiol. 83(4):1370-1382, 1997.Pulmonary arterial tree structures related toblood flow heterogeneity were simulated by using a symmetrical,bifurcating model in three-dimensional space. The branch angle (),daughter-parent length ratio(r_L), branchrotation angle (), and branch fraction of parent flow () for asingle bifurcation were defined and repeated sequentially through 11 generations. With  fixed at 90°, tree structures were generatedwith  between 60 and 90°,r_L between 0.65 and 0.85, and an initial segment length of 5.6 cm and sectioned into1-cm³ samples for analysis. Bloodflow relative dispersions (RD%) between 52 and 42% and fractaldimensions (D_s)between 1.20 and 1.15 in 1-cm³samples were observed even with equal branch flows. When  0.5, RD% increased, butD_s eitherdecreased with gravity bias of higher branch flows or increased withrandom assignment of higher flows. Blood flow gradients along gravityand centripetal vectors increased with biased flow assignment of higherflows, and blood flows correlated negatively with distance only when   0.5. Thus a recursive branching vascular tree structuresimulated D_s andRD% values for blood flow heterogeneity similar to those observedexperimentally in the pulmonary circulation due to differences in thenumber of terminal arterioles per1-cm³ sample, but blood flowgradients and a negative correlation of flows with distance requiredunequal partitioning of blood flows at branchpoints.

     

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.

     

Analysis of respiratory water---a new method for evaluation of myocardial energy metabolism

Schwanke, Uwe, Harald Strauss, Gunther Arnold, and Jochen D. Schipke. Analysis of respiratory watera new method for evaluation of myocardial energy metabolism. J. Appl.Physiol. 81(5): 2115-2122, 1996.Aerobic ATPsynthesis via oxidative phosphorylation causes a proportionalproduction of respiratory water. Thus the amount of respiratory waterproduced at a given time should be a reliable measure of the currentATP demand of the mammalian myocardium. Respiratory water from isolatedrabbit hearts was labeled by using the stable oxygen isotope¹⁸O. The hearts were perfusedaccording to the method of Langendorff (O. Langendorff.Pfluegers Arch. 61: 291-332,1895) with¹⁸O₂-equilibratedKrebs-Henseleit solution. Control hearts were exclusively perfused withcarbogen-equilibrated Krebs-Henseleit solution. Myocardial tissue wasthen lyophilized; the extracted water and samples from the coronaryvenous effluent were converted toCO₂ by using the guanidinehydrochloride technique. The¹⁸O values within theCO₂ samples were determined bymass spectrometry and related to the standard mean ocean water(SMOW) scale. Compared with controlhearts, the ¹⁸O-labeled heartsexhibited a significant increase of¹⁸O values from tissue water(47.50 ± 0.64 vs. 40.35 ± 2.05SMOW; P < 0.05). The values were alsosignificantly increased in the coronary venous effluent after aperfusion time of only 50 s (47.50 ± 0.64 vs. 43.66 ± 0.91 SMOW;P < 0.05). Thus this firstadaptation of the guanidine hydrochloride technique on microlitersamples of myocardial tissue water and coronary venous effluentdemonstrates that this method can be used to evaluate both respiratoryactivity and the kinetics of cardiac metabolic processes.