Gravitational independence of single-breath washout tests in recumbent dogs

To examine the mechanisms of lung filling and emptying, Ar-bolus and N2 single-breath washout tests were conducted in 10 anesthetized dogs (prone and supine) and in three of those dogs with body rotation. Transpulmonary pressure was measured simultaneously, allowing identification of the lung volume above residual volume at which there was an inflection point in the pressure-volume curve (VIP). Although phase IV for Ar was upward, phase IV for N2 was small and variable, especially in the prone position. No significant prone to supine differences in closing capacity for Ar were seen, indicating that airway closure was generated at the same lung volumes. The maximum deflections of phase IV for Ar and N2 from extrapolated phase III slopes were smaller in the prone position, suggesting more uniform tracer gas concentrations across the lungs. VIP was smaller than the closing volume for Ar, which is consistent with the effects of well-developed collateral ventilation in dogs. Body rotation tests in three dogs did not generally cause an inversion of phase III or IV. We conclude that in recumbent dogs regional distribution of ventilation is not primarily determined by the effect of gravity, but by lung, thorax, and mediastinum interactions and/or differences in regional mechanical properties of the lungs.     

Relation between Pulmonary Gas Exchange and Closing Volume before and after Substantial Weight Loss in Obese Subjects

Relations between expiratory reserve volume (ERV), closing volume (CV) as a percentage of vital capacity (CV/VC%), and pulmonary gas exchange have been investigated in the sitting and supine postures in eight severely obese subjects before and after substantial weight loss. CV/VC% exceeded predicted values but did not change with posture or weight loss; the increase could have been owing to the smoking habits of the subjects. Arterial oxygen pressure (PaO₂) was significantly less in the supine than in the sitting posture and improved after weight loss in six subjects. The reduction in PaO₂ was correlated with the extent to which dependent airways were closed within the range of tidal breathing, shown by increasing negativity of ERV-CV as a percentage of VC. A good correlation was also found between PaO₂ and ERV, an easier measurement for routine use. Improvement of pulmonary gas exchange occurred only in those patients who lost weight to within 30% in excess of ideal.     

Effect of airway closure on ventilation distribution

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80-90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502-2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.     

Effect of low-xenon and krypton supplementation on signal/noise of regional CT-based ventilation measurements.

Xenon computed tomography (Xe-CT) is used to estimate regional ventilation by measuring regional attenuation changes over multiple breaths while rebreathing a constant Xe concentration ([Xe]). Xe-CT has potential human applications, although anesthetic properties limit [Xe] to 相似文献   

Constant-flow ventilation in pigs

Constant-flow ventilation (CFV) is a ventilatory technique in which physiological blood gases can be maintained in dogs by a constant flow of fresh gas introduced via two catheters placed in the main-stem bronchi (J. Appl. Physiol. 53: 483-489, 1982). High-velocity gas exiting from the catheters can create uneven pressure differences in adjacent lung segments, and these pressure differences could lead to gas flow through collateral channels. To examine this hypothesis, we studied CFV in pigs, animals known to have a high resistance to collateral ventilation. In three pigs we examined steady-state gas exchange, and in six others we studied unsteady gas exchange at three flow rates (20, 35, and 50 l/min) and three catheter positions (0.5, 1.5, and 2.5 cm distal to the tracheal carina). During steady-state runs we were unable to attain normocapnia; the arterial CO2 partial pressure (PaCO2) was approximately 300 Torr at all flow rates and all catheter positions, compared with 20-50 Torr at similar flows and positions in dogs studied previously. The initial unsteady gas-exchange experiments indicated no consistent effect of catheter position or flow rate on the rate of rise of PaCO2. In three other pigs, the rates of rise of PaCO2 were compared with the rates observed with apneic oxygenation (AO). At the maximum flow and deepest position, the rate of rise of PaCO2 was lower during CFV than during AO. These data suggest that flow through collateral channels might be important in producing adequate gas transport during CFV; however, other factors such as airway morphometry and the effects of cardiogenic oscillations may explain the differences between the results in pigs and dogs.     

A new conventional and high-frequency ventilator for small animals

A pressure limited, time controlled ventilator has been designed especially for studies on experimental animals with severe respiratory distress syndrome (SRDS). Inspiration: Expiration (I:E) ratio (1:99-99:1) and frequency can be changed independently. Frequency ranged from 1 to 199/min in conventional ventilation (CV), while in high-frequency jet ventilation (HFJV) from 1 to 30 Hz. The gas delivery system consists of 3 magnetic valves (inspiration, expiration and HFJV, respectively) to ensure superposition of CV with HFJ or to use them separately. A monitoring unit switches off inspiration gas sources during HFJV if intratracheal pressure exceeds the alarm threshold. The device has been used in the following animal models: premature newborn rabbits with surfactant deficient lungs, emphysematous rats and guinea pigs as well as dogs and rabbits with SRDS due to lung lavage. Ventilation was most effective with an I:E ratio of 4:1 during pressure controlled CV, whereas during HFJV optimum gas exchange could be maintained with an I:E ratio of 1:4 and a frequency of 15 Hz in beagle dogs and 10 Hz in rabbits, respectively.     

Simple computer measurement of pulmonary VCO2 per breath.

Measurements of the volume of CO2 exhaled per breath (VCO2/br) are preferable to end-tidal PCO2, when the exhaled flow and CO2 waveforms may be changing during unsteady states, such as during alterations in positive end-expiratory pressure or alterations in cardiac output. We describe computer algorithms that determine VCO2/br from digital measurements of exhaled flow (including discontinuous signals common in anesthesia circuits) and CO2 concentration at the airway opening. Fractional concentration of CO2 is normally corrected for dynamic response and transport delay (TD), measured in a separate procedure. Instead, we determine an on-line adjusted TD during baseline ventilation. In six anesthetized dogs, we compared the determination of VCO2/br with a value measured in a simultaneous collection of expired gas. Over a wide range of tidal volume (180-700 ml), respiratory rate (3-30 min-1), and positive end-expiratory pressure (0-14 cmH2O), VCO2/br was more accurate with use of the adjusted TD than the measured TD (P less than 0.05).     

A general dimensionless equation of gas transport by high-frequency ventilation

To identify a general relationship between eucapnic oscillatory flow (Vosc) and frequency (f) in high-frequency ventilation (HFV), we searched the literature for eucapnic HFV data in different mammalian species. We found suitable results for rat, rabbit, monkey, dog, human, and horse, which we expressed in terms of two dimensionless variables, Q = Vosc/Va and F = f/(VA/VD), with VA the alveolar ventilation and VD the volume of the conducting airways. The experimental HFV data define the linear regression equation in Q = 0.54 In F + 0.92 (R = 0.94). Krogh's equation for conventional ventilation (CV), Vosc = VA + fVD, in dimensionless terms becomes Q = 1 + F, which is valid for low F. The intersection of the CV and HFV equations at F = 5.0 defines a transition frequency, ft = 5.0 (VA/VD). At that point the alveolar ventilation per breath, VA/f, represents 20% of VD, and tidal volume (VT) equals 1.20 VD. For eucapnia ft ranges from 5.9 Hz in the rat to 0.9 Hz in the dog. The dimensional form of our HFV equation, VA = 0.13 (VT/VD)1.2 (VTf) is very similar to other empirical equations reported for dogs in noneucapnic settings. Therefore the dimensionless equation should also be valid within a species at noneucapnic settings.     

Development of CO2 sensitivity: effects of gestational age, postnatal age, and sleep state

To determine the independent effects of sleep state, gestational age, and postnatal age on eucapnic ventilation and steady-state CO2 sensitivity, nine premature (146 +/- 3 days) and eight full-term (168 +/- 2 days) monkeys, Macaca nemestrina, from accurately timed conceptions were studied serially over the first 3 wk of life. Minute volume (VE)/kg,tidal volume (VT)/kg, and respiratory frequency were quantitated during rapid-eye-movement sleep (REM) and nonrapid-eye-movement sleep (NREM)in room air and when animals were breathing varied concentrations of cO2 in 21% O2. Eucapnic VE/kg and CO2 sensitivity [(deltaVE/kg)/delta PaCO2] increased progressively with advancing postnatal age during NREM sleep in grouped term and premature animals. CO2 sensitivity was not significantly different between REM and NREM sleep except in full-term animals at the highest postconceptual age studied (189 +/- 2 days) when [(delta VE/kg)/delta PaCO2] was lower in REM sleep than in NREM sleep (209 +/- 54 vs. 301 +/- 71 ml.min-1.kg-1.Torr-1; P less than 0.05, paired-t test). Gestational age had no measurable effect on eucapnic ventilation or CO2 sensitivity. These results support the hypothesis that REM sleep-induced depression of CO2 sensitivity develops in the neonatal monkey with advancing postconceptual age.     

Pulmonary gas exchange in panting dogs

Pulmonary gas exchange during panting was studied in seven conscious dogs (32 kg mean body wt) provided with a chronic tracheostomy and an exteriorized carotid artery loop. The animals were acutely exposed to moderately elevated ambient temperature (27.5 degrees C, 65% relative humidity) for 2 h. O2 and CO2 in the tracheostomy tube were continuously monitored by mass spectrometry using a special sample-hold phase-locked sampling technique. PO2 and PCO2 were determined in blood samples obtained from the carotid artery. During the exposure to heat, central body temperature remained unchanged (38.6 +/- 0.6 degrees C) while all animals rapidly switched to steady shallow panting at frequencies close to the resonant frequency of the respiratory system. During panting, the following values were measured (means +/- SD): breathing frequency, 313 +/- 19 breaths/min; tidal volume, 167 +/- 21 ml; total ventilation, 52 +/- 9 l/min; effective alveolar ventilation, 5.5 +/- 1.3 l/min; PaO2, 106.2 +/- 5.9 Torr; PaCO2, 27.2 +/- 3.9 Torr; end-tidal-arterial PO2 difference [(PE' - Pa)O2], 26.0 +/- 5.3 Torr; and arterial-end-tidal PCO2 difference, [(Pa - PE')CO2], 14.9 +/- 2.5 Torr. On the basis of the classical ideal alveolar air approach, parallel dead-space ventilation accounted for 54% of alveolar ventilation and 66% of the (PE' - Pa)O2 difference. But the steepness of the CO2 and O2 expirogram plotted against expired volume suggested a contribution of series in homogeneity due to incomplete gas mixing.     

Effects of mechanical ventilation at low lung volume on respiratory mechanics and nitric oxide exhalation in normal rabbits.

Lung mechanics, exhaled NO (NOe), and TNF-alpha in serum and bronchoalveolar lavage fluid were assessed in eight closed and eight open chest, normal anesthetized rabbits undergoing prolonged (3-4 h) mechanical ventilation (MV) at low volume with physiological tidal volumes (10 ml/kg). Relative to initial MV on positive end-expiratory pressure (PEEP), MV at low volume increased lung quasi-static elastance (+267 and +281%), airway (+471 and +382%) and viscolelastic resistance (+480 and +294%), and decreased NOe (-42 and -25%) in closed and open chest rabbits, respectively. After restoration of PEEP, viscoelastic resistance returned to control, whereas airway resistance remained elevated (+120 and +31%) and NOe low (-25 and -20%) in both groups of rabbits. Elastance remained elevated (+23%) only in closed-chest animals, being associated with interstitial pulmonary edema, as reflected by increased lung wet-to-dry weight ratio with normal albumin concentration in bronchoalveolar lavage fluid. In contrast, in 16 additional closed- and open-chest rabbits, there were no changes of lung mechanics or NOe after prolonged MV on PEEP only. At the end of prolonged MV, TNF-alpha was practically undetectable in serum, whereas its concentration in bronchoalveolar lavage fluid was low and similar in animals subjected or not subjected to ventilation at low volume (62 vs. 43 pg/ml). These results indicate that mechanical injury of peripheral airways due to their cyclic opening and closing during ventilation at low volume results in changes in lung mechanics and reduction in NOe and that these alterations are not mediated by a proinflammatory process, since this is expressed by TNF-alpha levels.     

Local gas transport in eucapnic ventilation: effects of gravity and breathing frequency

The effects of body position and respiratory frequency (f) on regional gas transport during eucapnic conventional ventilation (CV) and high-frequency ventilation (HFV) were assessed from the washout of nitrogen 13 (13NN) using positron-emission tomography. In one protocol, six dogs were ventilated with CV or HFV at f = 6 Hz and tidal volume (VT) selected supine for eucapnia. A coronal cross section of the lung base was studied in the supine, prone, and right and left lateral decubitus positions. In a second protocol, six dogs were studied prone: apical and basal cross sections were studied in CV and in HFV with f = 3 and 9 Hz at eucapnic VT. Regional alveolar ventilation per unit of lung volume (spVr) was calculated for selected regions and analyzed for gravity-dependent cephalocaudal and right-to-left gradients. In both CV and HFV, nonuniformity in spVr was highest supine and lowest prone. In CV there were vertical gradients of spVr in all body positions: nondependent less ventilated than dependent regions, particularly in the supine position. In HFV there was a moderate vertical gradient in spVr in addition to a preferentially ventilated central region in all body positions. Overall lung spV was unaffected by body position in CV but in HFV was highest supine and lowest prone. Nonuniformity in eucapnic prone HFV was unaffected by f and always higher than in CV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of methodological and biological influences on the collection and composition of exhaled breath condensate

The purpose of this inter-species comparison (calves and pigs) was to identify methodological and biological influences on the collection and composition of exhaled breath condensate (EBC). A total of 352 EBC samples were collected, whilst variables of ventilation were registered in parallel. Partial pressure of carbon dioxide (pCO₂) and pH were analysed in non-degassed EBC samples. The concentration of total protein in EBC was measured colorimetrically. In both species, lung function was evaluated before and after EBC collection. Statistical analyses were performed to study the effect of EBC collection on lung function and to identify the influence of ventilatory variables on the collection and composition of EBC. Collection of EBC did not affect lung function. Despite the volume of EBC collected per unit time being primarily dependent on ventilation per unit time, species-specific conditions during the EBC collection process resulted in different dependences of EBC collection from other variables of ventilation (i.e. maximal airflow during expiration or expired tidal volume kg^-1 body weight). The concentration of protein ml^-1 EBC increased with the expired volume per min and with peak expiratory flow. Although the pCO₂ in fresh EBC was significantly negatively dependent on the duration of collection, comparable pHs (5.6 - 6.2) were measured in EBC of both calves and pigs. The obtained data may help one standardize EBC collection in different species.     

Influence of expiratory flow on closing capacity at low expiratory flow rates.

Single-breath oxygen (SBO2) tests at expiratory flow rates of 0.2, 0.5, and 1.01/s were performed by 10 normal subjects in a body plethysmograph. Closing capacity (CC)--the absolute lung volume at which phase IV began--increased significantly with increases in flow. Five subjects were restudied with a 200-ml bolus of 100% N2 inspired from residual volume after N2 washout by breathing 100% O2 and similar results were obtained. An additional five subjects performed SBO2 tests in the standing, supine, and prone positions; closing volume (CV)--the lung volume above residual volume at which phase IV began--also increased with increases of expiratory flow. The observed increase in CC with increasing flow did not appear to result from dependent lung regions reaching some critical "closing volume" at a higher overall lung volume. In normal subjects, the phase IV increase in NI concentration may be caused by the asynchronous onset of flow limitation occurring initially in dependent regions.     

Cardiorespiratory effects of rapid saline infusion in normal man.

We have studied the cardiorespiratory effects of the rapid infusion (100 ml/min) of 2 liters of saline in four normal seated subjects. Cardiac output and pulmonary arterial pressure increased, while vital capacity (VC) and total lung capacity (TLC) decreased. There was an increase in closing volume (CV) without any detectable change in lung compliance or flow-volume characteristics. There was an increase in Pao2 during infusion period which can be related to better matching of ventilation to perfusion and to improved hemoglobin transport. In the recovery stage as cardiac output, pulmonary arterial pressure, TLC, and VC all returned toward control values CV remained high. In two subjects CV occurred within the normal tidal range of ventilation and in these two subjects Pao2 fell significantly below values obtained in the control period. The results suggest that rapid saline infusion in man can cause interstitial edema and lead to premature airway closure and hypoxemia.     

Effect of airways constriction on exhaled nitric oxide.

While airway constriction has been shown to affect exhaled nitric oxide (NO), the mechanisms and location of constricted airways most likely to affect exhaled NO remain obscure. We studied the effects of histamine-induced airway constriction and ventilation heterogeneity on exhaled NO at 50 ml/s (Fe(NO,50)) and combined this with model simulations of Fe(NO,50) changes due to constriction of airways at various depths of the lung model. In 20 normal subjects, histamine induced a 26 +/- 15(SD)% Fe(NO,50) decrease, a 9 +/- 6% forced expiratory volume in 1 s (FEV(1)) decrease, a 19 +/- 9% mean forced midexpiratory flow between 25% and 75% forced vital capacity (FEF(25-75)) decrease, and a 94 +/- 119% increase in conductive ventilation heterogeneity. There was a significant correlation of Fe(NO,50) decrease with FEF(25-75) decrease (P = 0.006) but not with FEV(1) decrease or with increased ventilation heterogeneity. Simulations confirmed the negligible effect of ventilation heterogeneity on Fe(NO,50) and showed that the histamine-induced Fe(NO,50) decrease was due to constriction, with associated reduction in NO flux, of airways located proximal to generation 15. The model also indicated that the most marked effect of airways constriction on Fe(NO,50) is situated in generations 10-15 and that airway constriction beyond generation 15 markedly increases Fe(NO,50) due to interference with the NO backdiffusion effect. These mechanical factors should be considered when interpreting exhaled NO in lung disease.     

Alveolar pressure inhomogeneity and gas exchange during constant-flow ventilation in dogs

Analysis of momentum transfer between inflow jets and resident gas during constant-flow ventilation (CFV) predicts inhomogeneity of alveolar pressures (PA) and volume, which might account for specific ventilation-variance in the lung. Using alveolar needles to measure pressures (PA) during CFV in eight anesthetized dogs with wide thoracotomy, we observed random dispersion of PA among lobes of up to 12.5 cmH2O. Within each lobe, the PA dispersion was up to 10 cmH2O at CFV of 90 l/min; when flow decreased, PA at all sites decreased, as did the intralobar dispersion. These pressure differences were not observed during conventional mechanical ventilation (CMV). During CFV with room air, dogs were hypoxemic [arterial PO2 (Pao2) 54 +/- 15 Torr] and the venous admixture (Qva/QT) was 50 +/- 15%. When inspiratory O2 fraction was increased to 0.4, Pao2 increased to 172 +/- 35 Torr and Qva/QT dropped to 13.5 +/- 8.4%, confirming considerable ventilation-perfusion (VA/Q) variance not observed during CMV. We conclude that momentum transfer between the inflow stream and resident gas caused inhomogeneities of alveolar pressures, volumes, and ventilation responsible for VA/Q variance and hypoxemia during CFV. Conceivably, the abnormal ventilation distribution is minimized by collateral ventilation and forces of interdependence between regions of high and low alveolar pressures. Momentum transfer also predicted the mucosal damage observed on histological evaluation of the bronchial walls near the site of inflow jet impact.     

Effect of lung volume on ventilation distribution

To examine the effect of preinspiratory lung volume (PILV) on ventilation distribution, we performed multiple-breath N2 washouts (MBNW) in seven normal subjects breathing 1-liter tidal volumes over a wide range of PILV above closing capacity. We measured the following two independent indexes of ventilation distribution from the MBNW: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency during that portion of the washout where 80-90% of the lung N2 had been cleared. Three of the subjects also performed single-breath N2 washouts (SBNW) by inspiring 1-liter breaths and expiring to residual volume at PILV = functional residual capacity (FRC), FRC + 1.0, and FRC - 0.5, respectively. From the SBNW we measured the phase III slope over the expired volume ranges of 0.75-1.0, 1.0-1.6, and 1.6-2.2 liters (S0.75, S1.0, and S1.6, respectively). Between a PILV of 0.92 +/- 0.09 (SE) liter above FRC and a PILV of 1.17 +/- 0.43 liter below FRC, Snf decreased by 61% (P less than 0.001) and alveolar mixing efficiency increased from 80 to 85% (P = 0.05). In addition, Snf and alveolar mixing efficiency were negatively correlated (r = 0.74). In contrast, over a similar volume range, S1.0 and S1.6 were greater at lower PILV. We conclude that, during tidal breathing in normal subjects, ventilation distribution becomes progressively more inhomogeneous at higher lung volumes over a range of volumes above closing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects on body position and cholinergic blockade on mechanics of collateral ventilation

We studied the effects of position and cholinergic blockade on the mechanics of collateral ventilation in anesthetized paralyzed dogs. Resistance to collateral flow (Rcoll) is higher when an obstructed segment is dependent than when it is nondependent. Decreases of Rcoll in response to the local infusion of low oxygen mixtures are greater in dependent regions. We conclude that 1) changes in position affect Rcoll directly through local changes in lung volume related to the gradient of pleural pressure; 2) responses of collateral channels to local concentrations of CO2 and O2 are determined by ventilation perfusion relationships, which vary at different heights in the lung; and 3) resting cholinergic tone in the anesthetized dog varies at different heights in the lung.     

Effect of the mechanical ventilatory cycle on thermodilution right ventricular volumes and cardiac output.

The purpose of this study was to evaluate right ventricular (RV) loading and cardiac output changes, by using the thermodilution technique, during the mechanical ventilatory cycle. Fifteen critically ill patients on mechanical ventilation, with 5 cmH(2)O of positive end-expiratory pressure, mean respiratory frequency of 18 breaths/min, and mean tidal volume of 708 ml, were studied with help of a rapid-response thermistor RV ejection fraction pulmonary artery catheter, allowing 5-ml room-temperature 5% isotonic dextrose thermodilution measurements of cardiac index (CI), stroke volume (SV) index, RV ejection fraction (RVEF), RV end-diastolic volume (RVEDV), and RV end-systolic volume (RVESV) indexes at 10% intervals of the mechanical ventilatory cycle. The ventilatory modulation of CI and RV volumes varied from patient to patient, and the interindividual variability was greater for the latter variables. Within patients also, RV volumes were modulated more by the ventilatory cycle than CI and SV index. Around a mean value of 3.95 +/- 1.18 l. min(-1). m(-2) (= 100%), CI varied from 87.3 +/- 5.2 (minimum) to 114.3 +/- 5.1% (maximum), and RVESV index varied between 61.5 +/- 17.8 and 149.3 +/- 34.1% of mean 55.1 +/- 17.9 ml/m(2) during the ventilatory cycle. The variations in the cycle exceeded the measurement error even though the latter was greater for RVEF and volumes than for CI and SV index. For mean values, there was an inspiratory decrease in RVEF and increase in RVESV, whereas a rise in RVEDV largely prevented a fall in SV index. We conclude that cyclic RV afterloading necessitates multiple thermodilution measurements equally spaced in the ventilatory cycle for reliable assessment of RV performance during mechanical ventilation of patients.