Reference values of pulmonary diffusing capacity for nitric oxide in an adult population.

Our objective was to create reference values for single-breath DLNO based on a sample of non-smoking healthy males and females using a short breath-hold time. The sample included 130 individuals varied in age (18-85 yr), height (149-190 cm), and weight (49.4-102.6 kg). The subjects performed single-breath-hold maneuvers at rest inhaling 41 +/- 6 ppm NO and a standard diffusion mixture. The breath-hold time was 5.5 +/ -0.6 s. Multiple linear regression with backward elimination of the independent variables age, weight, gender, and either measured lung volume (called alveolar volume or VA) or height revealed specific prediction equations for DLNO. Inserting VA instead of height into the regression equation determined how much of an abnormality of DLNO was due to gas exchange versus low lung volume. The predicted DLNO adjusted for lung volume (ml/min/mmHg) = DLNO = 73.1 + 17.26 x (VA)+17.56 x (gender) - 1.0 x (age). The predicted DLNO unadjusted for lung volume (ml/min/mmHg) = -20.1 + 1.167 x (height)+31.81 x (gender) - 1.21 x (age). For gender, 1 = males, 0 = females; VA = liters; height = cm. Age, gender and VA (lung volume) were the best predictors of DLNO and DLCO. Weight was not a good independent predictor of DLNO or DLCO. When normalizing for height and age, women have 650 ml lower forced vital capacity, 660 ml lower VA, and a 6 and 32 ml/min/mmHg lower DLCO and DLNO, respectively, compared to men. Normalizing for lung volume and age, women have, on average, a 3.2 and 18 ml/min/mmHg lower DLCO and DLNO, respectively, compared to men.     

Lung diffusion capacity for nitric oxide and carbon monoxide is impaired similarly following short-term graded exercise.

Study aimed to determine whether short-term graded exercise affects single-breath lung diffusion capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) similarly, and whether the DLNO/DLCO ratios during rest are altered post-exercise compared to pre-exercise. Eleven healthy subjects (age=29+/-6 years; weight=76.6+/-13.2 kg; height=177.9+/-13.2 cm; and maximal oxygen uptake or V(.-)(O(2max) = 52.7 +/- 9.3 ml kg(-1) min(-1))performed simultaneous single-breath DLNO and DLCO measurements at rest (inspired NO concentration=43.2+/-4.1 ppm, inspired CO concentration=0.30%) 15 min before and 2h after a graded exercise test to exhaustion (exercise duration=593+/-135 s). Resting DLNO and DLCO was similarly reduced 2h post-exercise (DLNO=-7.8+/-3.5%, DLCO=-10.3+/-6.9%, and P<0.05) due to reductions in pulmonary capillary blood volume (-11.3+/-9.0%, P<0.05) and membrane diffusing capacity for CO (-7.8+/-3.5%; P<0.05). The change in DLCO was reflected by the change in DLNO post-exercise such that 68% of the variance in the change in DLCO was accounted for by the variance in the change in DLNO (P<0.05). The DLNO/DLCO ratio was not altered post-exercise (5.87+/-0.37) compared to pre-exercise (5.70+/-0.34). We conclude that the decrease in single-breath DLNO and DLCO from pre- to post-exercise is similar, the magnitude of the change in DLCO closely reflects that of the change in DLNO, and single-breath DLNO/DLCO ratios are independent of the timing of measurement suggesting that using NO and CO transfer gases are valid in looking at short-term changes in lung diffusional conductance.     

Pulmonary NO uptake in interstitial lung disease

Because lung nitric oxide (NO) diffusing capacity (DL) represents alveolar-capillary gas diffusion, we queried as to whether disturbances of pulmonary gas exchange in interstitial lung disease (ILD) are appropriately reflected by using NO. In this pilot study, we applied the (15)N-labeled stable isotope (15)NO (relative abundance 0.37% of total NO) in order to ignore the endogenous NO production. In 10 ILD-outpatients, we measured DL (15)NO by performing the single-breath method. Lung function parameters as well as arterial oxygen partial pressure (PaO(2)) were also tested. Values of DL (15)NO ranged within 50-151 ml (15)NO/(mmHg min). Ratios of DL (15)NO/reference were between 43 and 108% of predicted data as taken from our previous work on healthy volunteers [Eur. J. Physiol. 446 (2003) 256]. We found a significant reduction of DL (15)NO/reference in five patients. Additionally, values of PaO(2) were significantly correlated to ratios of DL (15)NO/reference (adjusted R2 +/-SEE=0.407+/-8.051). In conclusion, (15)NO represents an appropriate indicator gas for reflecting an ILD-induced impairment of alveolar-capillary gas exchange.     

Chemiluminescent measurements of nitric oxide pulmonary diffusing capacity and alveolar production in humans.

Measurements of nitric oxide (NO) pulmonary diffusing capacity (DL(NO)) multiplied by alveolar NO partial pressure (PA(NO)) provide values for alveolar NO production (VA(NO)). We evaluated applying a rapidly responding chemiluminescent NO analyzer to measure DL(NO) during a single, constant exhalation (Dex(NO)) or by rebreathing (Drb(NO)). With the use of an initial inspiration of 5-10 parts/million of NO with a correction for the measured NO back pressure, Dex(NO) in nine healthy subjects equaled 125 +/- 29 (SD) ml x min(-1) x mmHg(-1) and Drb(NO) equaled 122 +/- 26 ml x min(-1) x mmHg(-1). These values were 4.7 +/- 0.6 and 4.6 +/- 0.6 times greater, respectively, than the subject's single-breath carbon monoxide diffusing capacity (Dsb(CO)). Coefficients of variation were similar to previously reported breath-holding, single-breath measurements of Dsb(CO). PA(NO) measured in seven of the subjects equaled 1.8 +/- 0.7 mmHg x 10(-6) and resulted in VA(NO) of 0.21 +/- 0.06 microl/min using Dex(NO) and 0.20 +/- 0.6 microl/min with Drb(NO). Dex(NO) remained constant at end-expiratory oxygen tensions varied from 42 to 682 Torr. Decreases in lung volume resulted in falls of Dex(NO) and Drb(NO) similar to the reported effect of volume changes on Dsb(CO). These data show that rapidly responding chemiluminescent NO analyzers provide reproducible measurements of DL(NO) using single exhalations or rebreathing suitable for measuring VA(NO).     

Pulmonary diffusing capacities for nitric oxide and carbon monoxide determined by rebreathing in dogs

Pulmonary diffusing capacities (DL) of NO and CO were determined simultaneously from rebreathing equilibration kinetics in anesthetized paralyzed supine dogs (mean body wt 20 kg) after denitrogenation (replacement of N2 by Ar). During rebreathing the dogs were ventilated in closed circuit with a gas mixture containing 0.06% NO, 0.06% 13C18O, and 1% He in Ar for 15 s, with tidal volume of 0.5 liter and frequency of 60/min. The partial pressures of NO, 13C18O, 16O18O, N2, Ar, CO2, and He in the trachea were continuously analyzed by mass spectrometry. Measurements were performed at various O2 levels characterized by the mean end-expired PO2 during rebreathing (PE'O2). In control conditions ("normoxia," PE'O2 = 67 +/- 8 Torr) the following mean +/- SD values were obtained (in ml.min-1.Torr-1): DLNO = 52.4 +/- 11.0 and DLCO = 15.4 +/- 2.9. In hypoxia (PE'O2 = 24 +/- 7 Torr) DLNO increased by 11 +/- 8% and DLCO by 19 +/- 10%, and in hyperoxia (PE'O2 = 390 +/- 26 Torr) DLNO decreased to 87 +/- 3% and DLCO to 56 +/- 8% with respect to values in normoxia. DLNO/DLCO of 3.24 +/- 0.06 (hypoxia), 3.38 +/- 0.31 (normoxia), and 5.54 +/- 1.04 (hyperoxia) were significantly higher than the NO/CO Krogh diffusion constant ratio (1.92) predicted for simple diffusion through aqueous layers. With increasing O2 uptake elicited by 2,4-dinitrophenol, DLNO and DLCO increased and DLNO/DLCO remained close to unchanged. The results suggest that the combined effects of diffusion and chemical reaction with hemoglobin limit alveolar-capillary transport of CO. If it is assumed that reaction kinetics of NO with hemoglobin (known to be extremely fast) are not rate limiting for NO uptake, the contribution of the slow chemical reaction with hemoglobin to the total CO uptake resistance (= 1/DLCO) was estimated to be 38% in hypoxia, 41% in normoxia, and 64% in hyperoxia. The various factors expected to restrict the validity of this analysis are discussed, in particular the effects of functional inhomogeneity.     

Involvement of nitric oxide in elicitor-induced defense responses and secondary metabolism of Taxus chinensis cells

This work was to characterize the generation of nitric oxide (NO) in Taxus chinensis cells induced by a fungal elicitor extracted from Fusarium oxysporum mycelium and the signal role of NO in the elicitation of plant defense responses and secondary metabolite accumulation. The fungal elicitor at 10-100 microg/ml (carbohydrate equivalent) induced a rapid and dose-dependent NO production in the Taxus cell culture, which exhibited a biphasic time course, reaching the first plateau within 1 h and the second within 12 h of elicitor treatment. The NO donor sodium nitroprusside potentiated elicitor-induced H2O2 production and cell death but had little influence on elicitor-induced membrane K+ efflux and H+ influx (medium alkalinization). NO inhibitors Nomega-nitro-L-arginine and 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide partially blocked the elicitor-induced H2O2 production and membrane ion fluxes. Moreover, the NO inhibitors suppressed elicitor-induced activation of phenylalanine ammonium-lyase and accumulation of diterpenoid taxanes (paclitaxel and baccatin III). These results suggest that NO plays a signal role in the elicitor-induced responses and secondary metabolism activities in the Taxus cells.     

High tidal volume upregulates intrapulmonary cytokines in an in vivo mouse model of ventilator-induced lung injury.

Mechanical ventilation has been demonstrated to exacerbate lung injury, and a sufficiently high tidal volume can induce injury in otherwise healthy lungs. However, it remains controversial whether injurious ventilation per se, without preceding lung injury, can initiate cytokine-mediated pulmonary inflammation. To address this, we developed an in vivo mouse model of acute lung injury produced by high tidal volume (Vt) ventilation. Anesthetized C57BL6 mice were ventilated at high Vt (34.5 +/- 2.9 ml/kg, mean +/- SD) for a duration of 156 +/- 17 min until mean blood pressure fell below 45 mmHg (series 1); high Vt for 120 min (series 2); or low Vt (8.8 +/- 0.5 ml/kg) for 120 or 180 min (series 3). High Vt produced progressive lung injury with a decrease in respiratory system compliance, increase in protein concentration in lung lavage fluid, and lung pathology showing hyaline membrane formation. High-Vt ventilation was associated with increased TNF-alpha in lung lavage fluid at the early stage of injury (series 2) but not the later stage (series 1). In contrast, lavage fluid macrophage inflammatory protein-2 (MIP-2) was increased in all high-Vt animals. Lavage fluid from high-Vt animals contained bioactive TNF-alpha by WEHI bioassay. Low-Vt ventilation induced minimal changes in physiology and pathology with negligible TNF-alpha and MIP-2 proteins and TNF-alpha bioactivity. These results demonstrate that high-Vt ventilation in the absence of underlying injury induces intrapulmonary TNF-alpha and MIP-2 expression in mice. The apparently transient nature of TNF-alpha upregulation may help explain previous controversy regarding the involvement of cytokines in ventilator-induced lung injury.     

Ventilatory responses to temperature variation in the fresh water turtle,Mauremys caspica leprosa

A study of lung gas exchange in the fresh water turtle Mauremys caspica leprosa at normal physiological body temperatures (15, 25 and 35 °C) was extended to extreme temperatures (5 and 40 °C) to determine whether the direct relationship between body temperature and ventilatory response found in many lung-breathing ectotherms including other chelonian species was maintained. From 5 to 35 °C the lung ventilation per unit of O₂ uptake and CO₂ removed declined with temperature. Consequently, lung CO₂ partial pressure increased with temperature. Its value was maintained within narrow limits at each thermal constant, suggesting a suitable control throughout the complete ventilatory cycle. At 40 °C the ventilatory response showed the opposite trend. The ratios of ventilation to lung gas exchange increased compared to their values at 35 °C. The impact of this increased breathing-lowering the estimated mean alveolar CO₂ partial pressure-was nevertheless less than expected due to an increase in calculated physiological dead space. This suggests that the relative hyperventilation in response to hyperthermia found in Mauremys caspica leprosa is related to evaporative heat loss.Abbreviations BTPS body temperature, ambient pressure, saturated with water vapour - CTM critical thermal maximum - F_N2 fractional concentration of nitrogen - PA _CO2or PL _CO2 alveolar or lung CO₂ pressure - PA_O2or PL_O2 alveolar or lung O₂ pressure - PI_O2 inspired O₂ pressure - R respiratory exchange ratio - STPD standard temperature, standard pressure, dry - T _a ambient temperature - T _b body temperature - VA alveolar ventilation - VA/VCO₂ relative alveolar ventilation (alveolar ventilation per unit of CO₂ removed) - VO₂ O₂ uptake - VCO₂ CO₂ output - V _D anatomical dead space volume - V _D physiological dead space volume - VE/VO₂ ventilatory equivalent for O₂ - VE pulmonary ventilation or expiratory minute volume - VE/VCO₂ ventilatory equivalent for CO₂ - V _T tidal volume     

Mechanism of arterial hypoxemia following pulmonary thromboembolism in dogs.

Mongrel dogs (29) were anesthetized, paralyzed, and ventilated at a constant minute volume. AaD02 breathing air and 100% O2, venous admixture breathing air (Qva/Qt) and 100% O2 (Qs/Qt), single-breath diffusing capacity for CO (DLCO), and total pulmonary resistance (RL) and pulmonary compliance (CL) were measured before and after pulmonary embolization with autologus in vivo venous thrombi. Nine dogs were heparinized before embolization. In the 20 nonheparinized dogs AaDo2 breathing air increased from 11 to 26 mmHg, Qva/Qt from 4 to 22%, and Qs/At from 5 to 8%. DLCO decreased 24%, RL increased 43%, and CL fell 30%. In the nine heparinized dogs AaDo2 breathing air increased from 8 to 13 mmHg and Qva/Qt from 3 to 8%; Qs/Qt did not change. DLCO decreased 31%; RL and CL did not change significantly. The increase in Qva/Qt of 5% in the heparinized dogs was significantly less (P smaller than 0.001) than the increase of 18% in the nonheparinized dogs. These findings suggest that arterial hypoxemia following thromboembolism is due to ventilation-perfusion inequality caused by changes in lung mechanics.     

CO2 relaxes parenchyma in the liquid-filled rat lung.

CO(2) regulation of lung compliance is currently explained by pH- and CO(2)-dependent changes in alveolar surface forces and bronchomotor tone. We hypothesized that in addition to, but independently of, those mechanisms, the parenchyma tissue responds to hypercapnia and hypocapnia by relaxing and contracting, respectively, thereby improving local matching of ventilation (Va) to perfusion (Q). Twenty adult rats were slowly ventilated with modified Krebs solution (rate = 3 min(-1), 37 degrees C, open chest) to produce unperfused living lung preparations free of intra-airway surface forces. The solution was gassed with 21% O(2), balance N(2), and CO(2) varied to produce alveolar hypocapnia (Pco(2) = 26.1 +/- 2.4 mmHg, pH = 7.56 +/- 0.04) or hypercapnia (Pco(2) = 55.0 +/- 2.3 mmHg, pH = 7.23 +/- 0.02). The results show that lung recoil, as indicated from airway pressure measured during a breathhold following a large volume inspiration, is reduced approximately 30% when exposed to hypercapnia vs. hypocapnia (P < 0.0001, paired t-test), but stress relaxation and flow-dependent airway resistance were unaltered. Increasing CO(2) from hypo- to hypercapnic levels caused a substantial, significant decrease in the quasi-static pressure-volume relationship, as measured after inspiration and expiration of several tidal volumes, but hysteresis was unaltered. Furthermore, addition of the glycolytic inhibitor NaF abolished CO(2) effects on lung recoil. The results suggest that lung parenchyma tissue relaxation, arising from active elements in response to increasing alveolar CO(2), is independent of (and apparently in parallel with) passive tissue elements and may actively contribute to Va/Q matching.     

Pulmonary diffusing capacity for nitric oxide during exercise in morbid obesity

Morbidly obese individuals may have altered pulmonary diffusion during exercise. The purpose of this study was to examine pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) during exercise in these subjects. Ten morbidly obese subjects (age = 38 +/- 9 years, BMI = 47 +/- 7 kg/m(2), peak oxygen consumption or VO(2peak) = 2.4 +/- 0.4 l/min) and nine nonobese controls (age = 41 +/- 9 years, BMI = 23 +/- 2 kg/m(2), VO(2peak) = 2.6 +/- 0.9 l/min) participated in two sessions: the first measured resting O(2) and VO(2peak) for determination of wattage equating to 40, 75, and 90% oxygen uptake reserve (VO(2)R). The second session measured pulmonary diffusion from single-breath maneuvers of 5 s each, as well as heart rate (HR) and VO(2) over three workloads. DLNO, DLCO, and pulmonary capillary blood volume were larger in obese compared to nonobese groups (P 0.10). The morbidly obese have increased pulmonary diffusion per unit increase in VA compared with nonobese controls which may be due to a lower rise in VA per unit increase in VO(2) in the obese during exercise.     

Labeled carbon dioxide (C18O2): an indicator gas for phase II in expirograms.

Carbon dioxide labeled with 18O (C18O2) was used as a tracer gas for single-breath measurements in six anesthetized, mechanically ventilated beagle dogs. C18O2 is taken up quasi-instantaneously in the gas-exchanging region of the lungs but much less so in the conducting airways. Its use allows a clear separation of phase II in an expirogram even from diseased individuals and excludes the influence of alveolar concentration differences. Phase II of a C18O2 expirogram mathematically corresponds to the cumulative distribution of bronchial pathways to be traversed completely in the course of exhalation. The derivative of this cumulative distribution with respect to respired volume was submitted to a power moment analysis to characterize volumetric mean (position), standard deviation (broadness), and skewness (asymmetry) of phase II. Position is an estimate of dead space volume, whereas broadness and skewness are measures of the range and asymmetry of functional airway pathway lengths. The effects of changing ventilatory patterns and of changes in airway size (via carbachol-induced bronchoconstriction) were studied. Increasing inspiratory or expiratory flow rates or tidal volume had only minor influence on position and shape of phase II. With the introduction of a postinspiratory breath hold, phase II was continually shifted toward the airway opening (maximum 45% at 16 s) and became steeper by up to 16%, whereas skewness showed a biphasic response with a moderate decrease at short breath holding and a significant increase at longer breath holds. Stepwise bronchoconstriction decreased position up to 45 +/- 2% and broadness of phase II up to 43 +/- 4%, whereas skewness was increased up to twofold at high-carbachol concentrations. Under all circumstances, position of phase II by power moment analysis and dead space volume by the Fowler technique agreed closely in our healthy dogs. Overall, power moment analysis provides a more comprehensive view on phase II of single-breath expirograms than conventional dead space volume determinations and may be useful for respiratory physiology studies as well as for the study of diseased lungs.     

Hyperbaric oxygen toxicity: role of thromboxane.

Exposing rabbits for 1 h to 100% O2 at 4 atm barometric pressure markedly increases the concentration of thromboxane B2 in alveolar lavage fluid [1,809 +/- 92 vs. 99 +/- 24 (SE) pg/ml, P less than 0.001], pulmonary arterial pressure (110 +/- 17 vs. 10 +/- 1 mmHg, P less than 0.001), lung weight gain (14.6 +/- 3.7 vs. 0.6 +/- 0.4 g/20 min, P less than 0.01), and transfer rates for aerosolized 99mTc-labeled diethylenetriamine pentaacetate (500 mol wt; 40 +/- 14 vs. 3 +/- 1 x 10(-3)/min, P less than 0.01) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt; 10 +/- 3 vs. 1 +/- 1 x 10(-4)/min, P less than 0.01). Pretreatment with the antioxidant butylated hydroxyanisole (BHA) entirely prevents the pulmonary hypertension and lung injury. In addition, BHA blocks the increase in alveolar thromboxane B2 caused by hyperbaric O2 (10 and 45 pg/ml lavage fluid, n = 2). Combined therapy with polyethylene glycol- (PEG) conjugated superoxide dismutase (SOD) and PEG-catalase also completely eliminates the pulmonary hypertension, pulmonary edema, and increase in transfer rate for the aerosolized compounds. In contrast, combined treatment with unconjugated SOD and catalase does not reduce the pulmonary damage. Because of the striking increase in pulmonary arterial pressure to greater than 100 mmHg, we tested the hypothesis that thromboxane causes the hypertension and thus contributes to the lung injury. Indomethacin and UK 37,248-01 (4-[2-(1H-imidazol-1-yl)-ethoxy]benzoic acid hydrochloride, an inhibitor of thromboxane synthase, completely eliminate the pulmonary hypertension and edema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of intrapulmonary O(2) concentration by MR imaging of inhaled hyperpolarized helium-3.

Inhalation of hyperpolarized (3)He allows magnetic resonance imaging (MRI) of ventilated airspaces. (3)He hyperpolarization decays more rapidly when interacting with paramagnetic O(2). We describe a method for in vivo determination of intrapulmonary O(2) concentrations ([O(2)]) based on MRI analysis of the fate of measured amounts of inhaled hyperpolarized (3)He in imaged regions of the lung. Anesthetized pigs underwent controlled normoventilation in a 1.5-T MRI unit. The inspired O(2) fraction was varied to achieve different end-tidal [O(2)] fractions (FET(O(2))). With the use of a specifically designed applicator, (3)He (100 ml, 35-45% polarized) was administered at a predefined time within single tidal volumes. During subsequent inspiratory apnea, serial two-dimensional images of airways and lungs were acquired. At least once in each animal studied, the radio-frequency excitation used for imaging was doubled at constant FET(O(2)). Signal intensity measurements in regions of interest of the animals' lungs (volume range, 54-294 cm(3)), taken at two different radio-frequency excitations, permitted calculation of [O(2)] in these regions of interest. The [O(2)] fractions in the regions of interest correlated closely with FET(O(2)) (R = 0.879; P < 0.0001). O(2)-sensitive (3)He-MRI may allow noninvasive study of regional distribution of ventilation and alveolar PO(2) in the lung.     

Display of the alveolar plateau of single-breath tests in "dilution index" format

In 1949, Fowler (J. Appl. Physiol. 2: 283-299) advocated calculation of a "dilution index" from data of the alveolar plateau of single-breath tests; the calculation provides an estimate of the dilution of resident gas in the lung that gave rise to the observed concentrations. In this communication, we show that the calculation can be applied to conventional single-breath tests where O2 is inhaled by air-breathing persons, and we illustrate the principle with vital capacity breaths of a mixture that contained a low concentration of neon. The dilution was approximately 3:1 in young subjects (20-30 yr), as if a vital capacity of 6 liters were mixed with a residual volume of 2 liters. The dilution was less, 2:1, in older subjects (56 yr) and tended to become as low as 1:1 during emptying of the closing volume. In addition to being more informative, the dilution index format allows common sense comparison of alveolar plateau levels and slopes when single-breath tests are done by various methods.     

Cardiovascular responses to lower body negative pressure in trained and untrained older men.

To determine whether aerobic conditioning alters the orthostatic responses of older subjects, cardiovascular performance was monitored during graded lower body negative pressure in nine highly trained male senior athletes (A) aged 59-73 yr [maximum O2 uptake (VO2 max) = 52.4 +/- 1.7 ml.kg-1 x min-1] and nine age-matched control subjects (C) (VO2 max = 31.0 +/- 2.9 ml.kg-1 x min-1). Cardiac volumes were determined from gated blood pool scintigrams by use of 99mTc-labeled erythrocytes. During lower body negative pressure (0 to -50 mmHg), left ventricular end-diastolic and end-systolic volume indexes and stroke volume index decreased in both groups while heart rate increased. The decreases in cardiac volumes and mean arterial pressure and the increase in heart rate between 0 and -50 mmHg were significantly less in A than in C. For example, end-diastolic volume index decreased by 32 +/- 4 ml in C vs. 14 +/- 2 ml in A (P < 0.01), mean arterial pressure declined 7 +/- 5 mmHg in C and increased by 5 +/- 3 mmHg in A (P < 0.05), and heart rate increased 13 +/- 3 beats/min in C and 7 +/- 1 beats/min in A (P < 0.05). These data suggest that increased VO2 max among older men is associated with improved orthostatic responses.     

Pulmonary vasodilation by inhaled nitric oxide after endothelial injury.

Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation we studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 +/- 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 +/- 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 +/- 1 and 9 +/- 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa (-9 +/- 3 and -4 +/- 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation.     

Functional residual capacity and ventilation homogeneity in mechanically ventilated small neonates.

A modification of a computerized tracer gas (SF6) washout method was designed for serial measurements of functional residual capacity (FRC) and ventilation homogeneity in mechanically ventilated very-low-birth-weight infants with tidal volumes down to 4 ml. The method, which can be used regardless of the inspired O2 concentration, gave accurate and reproducible results in a lung model and good agreement compared with He dilution in rabbits. FRC was measured during 2-4 cmH2O of positive end-expiratory pressure (PEEP) in 15 neonates (700-1,950 g), most of them with mild-to-moderate respiratory distress syndrome. FRC increased with body weight and decreased (P less than 0.05) with increasing O2 requirement. Change to zero end-expiratory pressure caused an immediate decrease in FRC by 29% (P less than 0.01) and gave FRC (ml) = -1.4 + 17 x weight (kg) (r = 0.83). Five minutes after PEEP was discontinued (n = 12), FRC had decreased by a further 16% (P less than 0.01). The washout curves indicated a near-normal ventilation homogeneity not related to changes in PEEP. This was interpreted as evidence against the presence of large volumes of trapped alveolar gas.     

The lung diffusing capacity for nitric oxide in rats is increased during endotoxemia.

Rats, when injected with endotoxin, begin to exhale nitric oxide (NO) within 1 h. This study measured the diffusing capacity for NO in the lungs of rats (DL(NO)) under both control and endotoxemic conditions, and it also estimated the rate at which endogenous NO (VP(NO)) enters the distal compartment of the lung, both in control rats and during endotoxemia. DL(NO) increased from 0.68 +/- 0.12 (SE) ml. min(-1). mmHg(-1) in control rats to 1.17 +/- 0.25 ml. min(-1). mmHg(-1) in endotoxemic rats. VP(NO) was 2.6 +/- 0.5 nl/min in control rats and attained a value of 218.6 +/- 50.1 nl/min at the height of NO exhalation 3 h after the endotoxin. We suggest that increased DL(NO) reflects an increase in pulmonary membrane diffusing capacity, caused by a pulmonary hypertension that is due to neutrophil aggregation in the lung capillaries. DL(NO) may also be increased by an enlarged pulmonary capillary volume because of the vasodilatory effects of the endogenous NO that is produced by the lung in response to the endotoxin. NO production by the lungs in response to endotoxin is unique in that it is the only situation reported to date in which pathologically induced increases in NO exhalation originate from the alveolar compartment of the lung, as opposed to the small conducting airways.     

Hypoxic pulmonary vasoconstriction does not affect hydrostatic pulmonary edema formation

We studied the effects of regional hypoxic pulmonary vasoconstriction (HPV) on lobar flow diversion in the presence of hydrostatic pulmonary edema. Ten anesthetized dogs with the left lower lobe (LLL) suspended in a net for continuous weighing were ventilated with a bronchial divider so the LLL could be ventilated with either 100% O2 or a hypoxic gas mixture (90% N2-5% CO2-5% O2). A balloon was inflated in the left atrium until hydrostatic pulmonary edema occurred, as evidenced by a continuous increase in LLL weight. Left lower lobe flow (QLLL) was measured by electromagnetic flow meter and cardiac output (QT) by thermal dilution. At a left atrial pressure of 30 +/- 5 mmHg, ventilation of the LLL with the hypoxic gas mixture caused QLLL/QT to decrease from 17 +/- 4 to 11 +/- 3% (P less than 0.05), pulmonary arterial pressure to increase from 35 +/- 5 to 37 +/- 6 mmHg (P less than 0.05), and no significant change in rate of LLL weight gain. Gravimetric confirmation of our results was provided by experiments in four animals where the LLL was ventilated with an hypoxic gas mixture for 2 h while the right lung was ventilated with 100% O2. In these animals there was no difference in bloodless lung water between the LLL and right lower lobe. We conclude that in the presence of left atrial pressures high enough to cause hydrostatic pulmonary edema, HPV causes significant flow diversion from an hypoxic lobe but the decrease in flow does not affect edema formation.