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Gas mixing in dog lungs during high frequency ventilation studied by partial washout-single exhalation technique.

Gas mixing was studied in 10 anesthetized paralyzed dogs during high-frequency low tidal ventilation (HFV). After simultaneous washin of ethane (1%) and washout of resident argon (0.9%) the gas inflow was switched to atmospheric air for varied time intervals leading to varied levels of C2H6 washout and Ar washin. After the stop of HFV at predetermined test gas washout/washin levels, a constant-flow exhalation by a servo ventilator was performed and expirograms of C2H6 and Ar were recorded. Measurements were performed at varied ventilation frequencies (10-40 Hz), stroke volumes (20-40 ml), lung volumes (730-830 ml), expiratory flow rates (0.1-0.01 L/sec), breath-holding prior to exhalation (0-12 sec) and test gas washout levels achieved by varying the washout time (1 to 65 sec) before onset of exhalation. The expirograms showed a close to linearly rising alveolar plateau. They were analyzed for series dead space and alveolar slope which was normalized to the initial-to-final partial pressure difference. The normalized slopes of C2H6 washout and Ar washin were averaged, whereby the effect of shrinking lung volume due to continuing CO2/O2 exchange at low R was assumed to be suppressed. The slope was little affected by changes of stroke volume, decreased slightly with increasing frequency, and decreased considerably with breath-holding or increasing lung volume. As washout progressed, the alveolar slope first increased, attained a maximum at about half-washout and thereafter decreased. The finite values of the alveolar slope indicated that intrapulmonary gas mixing during HFV was incomplete. The slopes were larger than expected from diffusion calculations on symmetrically branching lung models. The behavior of the slope at varied washout levels suggested involvement of parallel ventilation/volume inhomogeneity coupled with sequential emptying.

Animals↗

Estimating exercise DLO2 and diffusion limitation in patients with interstitial fibrosis.

Inert gas elimination studies in interstitial fibrosis ascribe all of the resting and most (58-83%) of the exercise (A-a)PO2 difference to ventilation-perfusion inequality. The previous paper (Hughes, J.M.B., D.N.A. Lockwood, H.A. Jones and R.J. Clark, (1991) Respir. Physiol. 83:155-166) [corrected] suggests from estimates of global DLO2/Q beta ratios a larger role for diffusion limitation on exercise. Gas exchange data from that paper was analyzed at rest and on exercise for five patients with interstitial fibrosis. Hypoxemia at rest was attributed to VA/Q inequality which was quantified using a log-normal lung model. DLO2 was calculated by Bohr integration. The base 10 LogSDQ at rest averaged 0.5 +/- 0.1 (SEM). On the assumption that VA/Q inequality remained unchanged on exercise, DLO2 (exercise) was estimated to be 14.3 +/- 1.9 ml.min-1.Torr-1. At that level of DLO2, diffusion limitation accounted for 36% +/- 8(SEM)% of the total (A-a)PO2 difference using the log-normal VA/Q model. But estimates of DLO2/Q beta assuming a homogenous lung, ascribed 96% of the (A-a)PO2 gradient on exercise to diffusion limitation. This discrepancy was shown to be related to the shape of the oxygen equilibrium curve and high alveolar PO2 values. On the other hand, analysis in terms of oxygen contents showed that 68 +/- 5% of the (A-a) content difference was accounted for by diffusion limitation. This differs substantially from estimates based on partial pressure alone.

Aged↗

Diffusion and perfusion limitation in alveolar O2 exchange: shape of the blood O2 equilibrium curve.

The limitations imposed by diffusion (Ldiff) and perfusion (Lperf) on alveolar gas exchange can be estimated using a simple model of alveolar-capillary gas transfer (Piiper and Scheid (1981) Respir, Physiol. 46: 193-208). These limitations indicate the fractional increase of gas exchange that would occur by raising pulmonary conductances for diffusion or perfusion to functionally infinite values. The (simple) model assumes linear relations between concentration and partial pressure for the gases studied. We have investigated in this study the effects of this assumption for estimating Ldiff and Lperf for O2 whose blood equilibrium curve is particularly non-linear in normoxia. The calculations suggest that Lperf is only slightly overestimated by the assumption of linear blood O2 binding. For Ldiff, there is a significant overestimation in normoxia, but in hypoxia the linear equilibrium curve yields sufficiently accurate estimates. Calculations for data estimated for man on the summit of Mt. Everest suggest that alveolar O2 uptake in deep hypoxia at rest is mainly limited by perfusion and to a lesser degree by diffusion (Lperf greater than Ldiff). For the sustained exercise of climbing, on the other hand, diffusion limitation is more prominent than perfusion limitation (Ldiff greater than Lperf). Large values of Ldiff are estimated for normoxic O2 uptake across the skin of the gill-less and lung-less salamander, and here, the effects of the alinearity of the O2 equilibrium curve are pronounced. It is concluded that the simplified model of alveolar-capillary gas transfer, with linear O2 equilibrium curve, can be very useful to estimate diffusion and perfusion limitations from experimental data.

Altitude↗

Effect of blood flow on capillary transit time and oxygenation in excised rabbit lung.

We used an isolated perfused lung preparation of the rabbit to study the effect of increasing blood flow on pulmonary capillary transit time by two methods. In one method, capillary transit time was measured from fluorescent dye dilution curves from arterioles and venules of the subpleural microcirculation. Values of transit time were similar to those for the whole lung determined by dividing capillary blood volume by blood flow. Capillary transit times averaged 0.50-0.62 sec at a control blood flow of 80 ml min-1 kg-1 and decreased to 0.14-0.18 sec as blood flow increased to 6 times control. To determine whether the reduced transit time would limit O2 transport, we studied the effect of blood flow on oxygenation. Two isolated rabbit lungs were perfused in series. Blood from one lung deoxygenated by ventilation with a N2-CO2 mixture was oxygenated by the test lung ventilated with air. Ventilation was matched to blood flow. PO2 and PCO2 were measured in blood flowing into and out of the test lung. At all flows, no significant alveolar gas-to-end-capillary blood PO2 gradient (A-aDO2) was measured. The isolated perfused rabbit lung showed no transit time limitation to oxygenation for blood flows that are consistent with heavy exercise in vivo.

Animals↗

One-year inhalation toxicity study of chlorine in rhesus monkeys (Macaca mulatta).

Chlorine (Cl2) gas is a potentially lung-damaging irritant which is used in the chemical, plastics, and paper industries. There are no data published using experimental animals on the chronic inhalation toxicity of chlorine. The purpose of this study was to investigate the chronic effects of Cl2 inhalation in Rhesus monkeys (Macaca mulatta). Rhesus monkeys were exposed to concentrations of 0, 0.1, 0.5, or 2.3 ppm Cl2 for 6 hr per day. 5 days per week for 1 year. Pulmonary physiology (pulmonary diffusing capacity and distribution of ventilation), body weights, urinalysis, electrocardiographs, hematology, and clinical chemistry were evaluated monthly during the study. Blood gas evaluations were performed at 3-month intervals during the study. Histopathologic, ophthalmologic, and neurologic parameters were evaluated after the 1-year exposure period. Monkeys exposed to 2.3 ppm Cl2 exhibited signs of ocular irritation during the daily exposures and a superficial conjunctival irritation was present in the 2.3 ppm group after the 1-year exposure regimen. Treatment-induced lesions revealed by histopathology were confined to the respiratory tract. Lesions associated with the nasal parasite Anatrichosoma spp. were present in the region of squamous epithelium of the nasal vestibule and did not interfere with interpretation of Cl2-induced effects. Treatment-induced histopathologic changes were found in the respiratory epithelium of the nasal passages and trachea and were limited to focal, concentration-related epithelial hyperplasia with loss of cilia and decreased numbers of goblet cells in affected areas. These changes in the nose and trachea were focal and mild in monkeys exposed to 2.3 ppm and were not found in all animals in these exposure groups. Tracheal lesions were confined to the 2.3 ppm group. The lesions observed at 2.3 ppm were not present in all animals. At the lower Cl2 concentrations, similar though less prominent respiratory epithelial lesions were observed. The latter changes were very minimal and were confined to the nasal passages of some treated monkeys and one male control animal. The results of this study indicate that 2.3 ppm chlorine acts as an upper respiratory irritant in monkeys, while 0.5 and 0.1 ppm induce changes of questionable clinical significance. Furthermore, the monkey appears to be less sensitive than the rat to chlorine toxicity.

Administration, Inhalation↗

Does the technique of cardiopulmonary bypass affect lung water content?

Several efforts have been made to improve the technique of cardiopulmonary bypass (CPB), including the use of pulsatile flow and the modification of cannulation technique. The present study focused upon extravascular lung water (EVLW) in 60 aortocoronary bypass patients subjected to four different perfusion techniques during CPB: group 1 (n = 15): non-pulsatile flow and standard cannulation; group 2 (n = 15); pulsatile flow and standard cannulation; group 3 (n = 15): nonpulsatile flow and monoatrial cannulation (i.e., always "partial" bypass during CPB); group 4 (n = 15): pulsatile flow and monoatrial cannulation. EVLW content was measured using the double-indicator dilution technique with indocyanine green; in addition, various hemodynamic and laboratory variables were measured. Lung water content rose above normal values (mean: 5.79 +/- 0.33 ml/kg) only in the groups submitted to the standard cannulation technique, irrespective of whether the perfusion flow was pulsatile or not (group 1: + 27.4%; group 2: + 25.5%). Pulmonary gas exchange, too, was compromised only in these patients (PaO2 in group 1 -19% and in group 2 -17%; Qs/Qt in group 1 + 36 rel. % and in group 2 + 29 rel. %), whereas all patients with monoatrial cannulation and partial bypass throughout the CPB period showed no rise in EVLW content or Qs/Qt and no drop in PaO2. From the results of this study we conclude that pulsatile perfusion during open heart surgical procedure has no advantages in regard to lung water content. Monoatrial cannulation with partial bypass at all times during CPB, however, seems to be beneficial, probably owing to the maintenance of pulmonary circulation during the bypass period.

Aged↗

3He diffusion MRI of the lung.

RATIONALE AND OBJECTIVES: MR imaging of the restricted diffusion of laser-polarized 3He gas provides unique insights into the changes in lung microstructure in emphysema. RESULTS: We discuss measurements of ventilation (spin density), mean diffusivity, and the anisotropy of diffusion, which yields the mean acinar airway radius. In addition, the use of spatially modulated longitudinal magnetization allows diffusion to be measured over longer distances and times, with sensitivity to collateral ventilation paths. Early results are also presented for spin density and diffusivity maps made with a perfluorinated inert gas, C3F8. METHODS: Techniques for purging and imaging excised lungs are discussed.

Diffusion Magnetic Resonance Imaging↗

The influence of training on oxygen isotope fractionation in healthy subjects.

We determined the oxygen isotope fractionation in expired alveolar gas relative to inspired air (delta(A-I)) in eight young, healthy subjects at rest and at five levels of exercise up to maximal workload both before and after a training period of about 4 weeks which increased maximum oxygen uptake by about 10%. The data for delta(A-I) were used to compute the relative difference (deltaU) between the resistances of 16O18O and 16O2 for oxygen transport from the alveolar space and utilization in the mitochondria. Prior to training, deltaU decreased from 15 per thousand at rest to 5 per thousand at the highest level of exercise and after training from 12 to 5 per thousand. The difference between the results for deltaU before and after training was significant for rest (P < or = 5) but not for exercise conditions. Accordingly, we conclude that for exercise conditions the non-fractionating oxygen transport by blood flow to and the fractionating oxygen transport by diffusion in the muscles have improved by training to more or less the same degree. The decrease in deltaU in rest after training suggests that oxygen transport by diffusion in other tissues also benefits from the effects of training.

Adult↗

Inhomogeneity of ventilation leads to unpredictable errors in measured D(L)CO.

We evaluated the effects of inhomogeneity of ventilation on single-breath (SB), rebreathing (RB) and open circuit (OC) D(L)CO using a mathematical model consisting of two alveolar compartments and a common dead space. Inhomogeneity in ventilation was studied by altering inspired volume, initial alveolar volume and compartment size independently. When distribution of inspired volume between alveolar compartments was inhomogeneous (9:1), D(L)CO was underestimated by 35% for SB, 25% for RB, and 16% for OC, and there was an underestimation in V(A) of 9%, 15% and 9%, respectively. With inhomogeneity in initial alveolar volume there was an overestimation in D(L)CO of 13%, 7% and 11% for SB, RB and OC techniques and an underestimation of V(A) of 7%, 12% and 9%. Finally inhomogeneity of compartment size led to an underestimation of D(L)CO of 18%, 35% and 36% with no change in measured V(A). These results suggest D(L)CO measurements are sensitive to inhomogeneity of ventilation, and importantly, all techniques were at times, significantly in error.

Algorithms↗

Aerosols in the study of convective acinar mixing.

Convective mixing (CM) refers to the different transport mechanisms except Brownian diffusion that irreversibly transfer inspired air into resident air and can be studied using aerosol bolus inhalations. This paper provides a review of the present understanding of how each of these mechanisms contributes to CM. Original data of the combined effect of stretch and fold and gravitational sedimentation on CM are also presented. Boli of 0.5 microm-diameter particles were inhaled at penetration volumes (V(p)) of 300 and 1200 ml in eight subjects. Inspiration was followed by a 10-s breath hold, during which small flow reversals (FR) were imposed, and expiration. There was no physiologically significant dependence in dispersion and deposition with increasing FR. The results were qualitatively similar to those obtained in a previous study in microgravity in which it was speculated that the phenomenon of stretch and fold occurred during the first breathing cycle without the need of any subsequent FR.

Adult↗

Diffusion-weighted 19F-MRI of lung periphery: Influence of pressure and air-SF6 composition on apparent diffusion coefficients.

Lung functional magnetic resonance imaging (MRI) has become a reality using different inert hyperpolarized gases, such as 3He and 129Xe, which have provided an extraordinary boost in lung imaging and has also attracted interest to other chemically inert gaseous contrast agents. In this context, we have recently demonstrated the first diffusion-weighted images using thermally polarized inhaled sulfur hexafluoride (SF6) in small animals. The aim of this study was to evaluate whether or not the diffusion coefficient of this fluorinated gas is sensitive to pulmonary structure, gas concentration and air pressure in the airways. Diffusion coefficients of SF6 (both pure and in air mixtures) measured in vitro at different pressures and 20 degrees C showed an excellent agreement with theoretical values. Measurements of diffusion coefficients were also performed in vivo and post-mortem on healthy rats, achieving satisfactory signal-to-noise ratios (SNRs), and SF6 gas was found to be in an almost completely restricted diffusion regime in the lung, i.e., the transport by molecular diffusion is delayed by collisions with barriers such as the alveolar septa. This observed low diffusivity means that this gas will be less sensitive to structural changes in the lungs than other magnetic resonance sensitive gas such as 3He, particularly at human scale. However, it is still possible that SF6 plays a role since it opens a new structural window. Thus, the interest of researchers in delimiting the important limiting technical factors that makes this process very challenging is obvious. Among them, T2 relaxation is very fast, so gradient systems with very fast switching rate and probably large radiofrequency (RF) power and high field systems will be needed for hexafluoride to be used in human studies.

Animals↗

Bronchopulmonary circulation in d-transposition of the great arteries: possible role in genesis of accelerated pulmonary vascular disease.

Hemodynamic and angiograhic data from 209 patients with d-transposition of the great arteries were reviewed to estimate the incidence of prominent bronchopulmonary circulation and to explore its role in the genesis of accelerated pulmonary vascular disease in these patients. The degree of bronchopulmonary circulation was assessed visually by considering the extent of the pulmonary arterial opacification and the circulation to the left atrium. An initial survey study revealed a marked degree of collateral circulation in 20 of 138 patients with d-transposition having cardiac catheterization before age 2 years at the Hospital for Sick Children, Toronto, between 1967 and 1972. Detailed analysis of 71 additional patients with d-transposition aged 1 week to 72 months (mean 17 months) studied at Children's Memorial Hospital, Chicago, between 1967 and 1974 showed collateral circulation of marked degree in 23 and of mild degree in 14. The bronchopulmonary collateral vessels were more freqently demonstrated in the patients with intact ventricular septum than in those with ventricular septal defect or left ventricular outflow tract stenosis. In a prospective study in 12 of 15 patients during cardiac catheterization the functional patency of the bronchopulmonary collateral circulation was demonstrated by obstructing pulmonary blood flow in the right or left pulmonary artery, or both, with an inflated balloon and obtaining from the pulmonary arterial segment distal to the occlusion blood with an oxygen saturation similar to that of the aorta. A hypothesis is presented concerning the role of systemic hypoxemia and local pulmonary hypoxemia induced by way of the bronchopulmonary collateral vessels and the bronchial arterial vasovasorum in promoting pulmonary vasoconstriction. It is suggested that increased pulmonary blood flow and pressure due to the physiologic features of ventricular septal defect, patent ductus arteriosus or transposition of the great vessels, in the face of this regionally increased hypoxemia results in accelerated pulmonary vascular disease.

Aortography↗

Uterine and whole body oxygen extractions in the pregnant rabbit under chronic steady-state conditions.

Seventeen pregnant rabbits were studied under conscious, unstressed conditions after catheterization of the right ventricle (RV), a femoral artery (A), and a uterine vein (UV). Respiratory gas tensions, pH, and oxygen saturations and contents were determined serially throughout the latter half of gestation. The uterine coefficient of oxygen extraction increased with gestational age (R = 0.86) and became 60.6% +/- 0.3% during the last 4 days of pregnancy. To compare uterine perfusion with whole body perfusion in relationship to oxygen demands, the (Ao2 - UVo2/Ao2 - RVo2) ratio was computed. The ratio was greater than or equal to 1 after 20 days of gestation, which demonstrated that in regard to oxygen demands the rabbit uterus is relatively underperfused compared to the rest of the maternal organism in the last part of pregnancy. A comparison with analogous data in other species demonstrates that the pregnant rabbit, like the guinea pig, has a much lower rate of uterine blood flow than does the pregnant sheep. These interspecies differences in the perfusion rate and oxygen extraction of the pregnant uterus are related to differences in placental structure.

Animals↗

Predicted versus observed maximum oxygen consumption early after lung resection.

BACKGROUND: The objective of this study was to identify the predictors of underestimation and overestimation of postoperative maximum oxygen consumption (VO(2)max). METHODS: A prospective analysis was performed on 229 patients who had 38 pneumonectomies, 171 lobectomies, and 20 segmentectomies. All patients performed a preoperative and postoperative (on average 9.2 days after surgery) maximal stair-climbing test. Predicted postoperative VO(2)max (ppoVO(2)max) was calculated on the basis of the number of functioning segments removed during operation. The patients were divided into three groups: group A (158 cases), patients with a ppoVO(2)max within 1 standard deviation of the observed postoperative VO(2)max; group B (56 cases), patients with a difference between the observed postoperative VO(2)max and ppoVO(2)max greater than 1 standard deviation (underestimation); and group C (15 cases), patients with a difference between ppoVO(2)max and the observed postoperative VO(2)max greater than 1 standard deviation (overestimation). Univariate and multivariate analyses were performed. RESULTS: The only significant predictor of underestimation was a high percentage of functional parenchyma removed during operation (p < 0.0001). The significant predictors of overestimation were a low percentage of functional parenchyma removed during operation (p = 0.01) and a high preoperative VO(2)max (p = 0.002). CONCLUSIONS: The prediction of postoperative VO(2)max was not accurate in all patients. Those with a large amount of functional lung tissue removed during operation tended to have a postoperative VO(2)max greater than expected. Conversely, those patients with a small amount of functional lung tissue resected tended to have a postoperative VO(2)max lower than predicted.

Adult↗

Diagnosis and long-term follow-up of major bronchial disruptions due to nonpenetrating trauma.

From 1966 through 1978, 13 patients were treated for major bronchial disruptions due to nonpenetrating trauma. In 10 patients the diagnosis was made early, and operation was carried out in all of them. Four of the 6 patients with main bronchus avulsion had primary repair and all 4 patients with lobar rupture underwent lobectomy. One patient had a pneumonectomy. There was 1 operative death. In 3 patients the diagnosis was made more than a month after the injury. A bronchoplastic repair was done in every patient. All 7 patients who had repair of a transected main bronchus were assessed 2 to 14 years after operation (average, 7 1/2 years). Flow-volume curves on air and air-helium were normal, indicating no major airway obstruction; this finding was confirmed by clinical and bronchoscopic examinations. Pulmonary diffusing capacity for carbon monoxide was also normal in all patients. Volume measurements by closed circuit method and by body plethysmography showed restriction in 1 patient but no major air trapping. Perfusion/ventilation scans showed homogeneous distribution of air and blood flow in the lung.

Adolescent↗