Cardiopulmonary adaptations to pneumonectomy in dogs. IV. Membrane diffusing capacity and capillary blood volume

Lung diffusing capacity for carbon monoxide (DLco) and its components, membrane diffusing capacity (Dmco) and capillary blood volume (Vc), as well as pulmonary blood flow (Qc), were measured at rest at several lung volumes and during treadmill exercise by a rebreathing technique in four adult dogs after right pneumonectomy (R-PNX) and in six matched control dogs (Sham) 6-12 mo after surgery. In both groups, lung inflation at rest was associated with a small increase in DLco and Dmco but not in Vc. After R-PNX, total DLco was lower by 30% at peak exercise compared with control values. When compared with DLco in a normal left lung, DLco in the remaining lung continued to increase along the normal relationship with respect to Qc up to a cardiac output equivalent to 34 l/min through both lungs of the Sham dog. There was no evidence of an upper limit of DLco being reached. The augmentation of DLco from rest to exercise was associated with corresponding increases in Dmco and Vc; after R-PNX, both Dmco and Vc continued to increase with respect to Qc along similar relationships as in control dogs without reaching an upper limit, suggesting a much larger alveolar-capillary reserve for gas exchange by diffusion than previously recognized. At higher levels of blood flow through the remaining lung, DLco was greater in adult dogs after R-PNX than after left pneumonectomy (Carlin et al. J. Appl. Physiol. 70: 135-142, 1991), suggesting that additional sources of compensation, e.g., lung growth, exist after removal of > 50% of lung.     

Rapid discontinuation of hypnotics in terminal cancer patients: a prospective study

BACKGROUND: Unexplained or primary pulmonary hypertension results in an obliteration and obstruction of resistance pulmonary arteries. In these patients gas exchange is impaired and the measurement of gas transfer for carbon monoxide is usually reduced. This has been thought to represent a reduction in pulmonary alveolar capillary blood volume (Vc). A single breath test, measuring simultaneously the uptake of both nitric oxide (NO) and carbon monoxide (CO), provides a simple and practical measurement of membrane diffusion (Dm) and Vc. METHODS: A standard single breath test for the measurement of gas transfer for carbon monoxide (TLCO) was adapted to include NO (40 ppm) in the inhaled gas mixture and a breath-hold time at total lung capacity of 7.5 seconds was used. Twelve patients with primary pulmonary hypertension and 10 similar normal volunteers were studied while seated at rest. RESULTS: The patients had reduced values for TLCO and TLNO. The mean (SD) value of Dm in the patients was 36.7 (32.1) mmol/min.kPa compared with 52.8 (23.9) mmol/min.kPa in the normal subjects. Vc in the patients was 0.03 (0.03) 1 and 0.06 (0.01) 1 in the normal subjects. CONCLUSIONS: The simultaneous measurement of NO and CO uptake is possible in healthy volunteers and patients with primary hypertension. In these patients capillary blood volume is reduced compared with normal subjects.     

Clinical correlates of an elevated diffusing capacity for carbon monoxide corrected for alveolar volume

The diffusing capacity for carbon monoxide is partially dependent on lung volume at which it is measured. As a consequence, the diffusing capacity for carbon monoxide is often indexed to the simultaneously measured lung volume (VA), giving rise to the term DL/VA. This reflects the diffusing capacity of carbon monoxide per unit area of lung parenchyma. The authors investigated the pulmonary function of 18 patients who had an elevated DL/VA in order to identify factors that could account for this abnormality. Sixteen of the 18 had a reduction in vital capacity. The vital capacity was reduced because of obesity, pleural disease, and diaphragmatic dysfunction. Eight of nine patients with a body mass index > 30 kg/m2 had a reduction in vital capacity. On the basis of these findings, we believe that an elevated DL/VA should alert the physician to the possibility of 1) an increase in pulmonary capillary blood volume (Vc) (obesity, polycythemia, negative pleural pressure), and 2) reduced VA that does not directly affect the pulmonary capillary bed (pleural disease, neuromuscular disease).     

Micronodules and emphysema in coal mine dust or silica exposure: relation with lung function

The aim of this study was to investigate the respective effects of micronodules and pulmonary emphysema, detected by computed tomography (CT), on lung function in workers exposed to silica and coal mine dust. Eighty-three subjects exposed to silica (n=35) or to coal mine dust (n=48), without progressive massive fibrosis, were investigated by high-resolution and conventional CT scans to detect micronodules and to quantify pulmonary emphysema by measuring the relative area of the lung with attenuation values lower than -950 Hounsfield units. Sixty-six (54.5%) subjects had evidence of micronodules on CT scans. Smokers had micronodules more rarely than nonsmokers. Significant correlations were found between the forced expiratory volume in one second (FEV(1); % predicted) (r=-0.41, p<0.001), FEV1/vital capacity (VC) (r=-0.61, p<0.001), diffusing capacity of the lung for carbon monoxide (DL,CO) (r=-0.36, p<0.001) and the extent of emphysema. No difference was demonstrated in the linear relationships between the extent of emphysema and the pulmonary function according to the type of exposure or the presence of micronodules on CT scans. This study suggests that micronodules detected by computed tomography have no influence, by themselves, on pulmonary function and that they should only be considered as a marker of exposure.     

Yeast culture volatiles as attractants for Rhodnius prolixus: electroantennogram responses and captures in yeast-baited traps

Seattle firefighters participate in a voluntary annual medical surveillance program including measurements of ventilatory capacity (FVC and FEV1) and single-breath diffusing capacity of carbon monoxide (DLCO). From 1989 to 1996, average % predicted DLCO (Crapo) for all participating firefighters declined from 94.4% (95% confidence interval [CI]: 93.4% to 95.5%) to 87.3% (95% CI: 86.2% to 88.3%), with no significant change in average FVC or FEV1. A random-effects regression model based on data from 812 firefighters with at least two annual sets of DLCO measurements showed the expected associations between DLCO and age, height, gender, race, ventilatory capacity, and smoking. In addition, two important temporal changes were observed, including, for an average firefighter, a large mean decline in DLCO of -1.02 ml/min/mm Hg associated with year of measurement, and a relatively smaller decline of -0.006 ml/min/mm Hg associated with number of fires fought. Although the stability of ventilatory capacity over time is reassuring, the marked temporal decline in diffusing capacity among this population of firefighters raises issues of concern. Interpretation of the observed decline poses a dilemma in terms of the reliability and efficacy of diffusing capacity as a screening tool, in whether DLCO is subject to unacceptable technical variability or whether it might provide more sensitive detection of early adverse respiratory effects of smoke inhalation.     

Role of reaction resistance in limiting carbon monoxide uptake in rabbit lungs

The contribution of reaction resistance to overall resistance to pulmonary carbon monoxide (CO) uptake [DLCO/(ThetaCO . Vc), where DLCO is lung CO diffusing capacity, ThetaCO is CO uptake conductance of erythrocytes, and Vc is pulmonary capillary blood volume] was determined in 10 anesthetized, paralyzed, and artificially ventilated rabbits. On the basis of the classical double-reciprocal equation of F. G. W. Roughton and R. E. Forster (J. Appl. Physiol. 11: 290-302, 1957), DLCO/(ThetaCO . Vc) was obtained by solving the relation DLCO/(ThetaCO . Vc) = 1 - 2/(DLNO/DLCO), where DLNO/DLCO represents the ratio between the respective single-breath diffusing capacities (DL) of nitric oxide (NO) and CO pulmonary capillary blood. The lungs of eight rabbits were inflated, starting from residual volume, by using 55 ml of indicator gas mixture (0.2% CO and 0.05% NO in nitrogen). DL values were calculated by taking the end-tidal partial pressures of CO and NO as analyzed by using a respiratory mass spectrometer. The overall value was DLCO/(ThetaCO . Vc) = 0.4 +/- 0.025 (mean +/- SD). Because of the use of O2-free indicator gas mixtures, the end-tidal O2 partial pressures were approximately 21 Torr. In one other rabbit, the application of 0.2% CO and 0.001% NO yielded DLCO/(ThetaCO . Vc) = 0.39; in the tenth rabbit, however, inspiratory volume was varied, and an identical value was found at functional residual capacity. We conclude that the contribution of reaction resistance to overall resistance to pulmonary CO uptake is independent of the inspiratory NO concentration used, including, with respect to the pertinent literature, the conclusion that in rabbits, dogs, and humans this contribution amounts to 40% when determined at functional residual capacity.     

Serial lung function and elastic recoil 2 years after lung volume reduction surgery for emphysema

STUDY OBJECTIVE: To evaluate serial lung function studies, including elastic recoil, in patients with severe emphysema who undergo lung volume reduction surgery (LVRS). To determine mechanism(s) responsible for changes in airflow limitation. METHODS: We studied 12 (10 male) patients aged 68+/-9 years (mean+/-SD) 6 to 12 months prior to and at 6-month intervals for 2 years after thoracoscopic bilateral LVRS for emphysema. RESULTS: At 2 years post-LVRS, relief of dyspnea remained improved in 10 of 12 patients, and partial or full-time oxygen dependency was eliminated in 2 of 7 patients. There was significant reduction in total lung capacity (TLC) compared with pre-LVRS baseline, 7.8+/-0.6 L (mean+/-SEM) (133+/-5% predicted) vs 8.6+/-0.6 L (144+/-5% predicted) (p=0.003); functional residual capacity, 5.6+/-0.5 L (157+/-9% predicted) vs 6.7+/-0.5 L (185+/-10% predicted) (p=0.001); and residual volume, 4.9+/-0.5 L (210+/-16% predicted) vs 6.0+/-0.5 L (260+/-13% predicted) (p=0.000). Increases were noted in FEV1, 0.88+/-0.08 L (37+/-6% predicted) vs 0.72+/-0.05 L (29+/-3% predicted) (p=0.02); diffusing capacity, 8.5+/-1.0 mL/min/mm Hg (43+/-3% predicted) vs 4.2+/-0.7 mL/min/mm Hg (18+/-3% predicted) (p=0.001); static lung elastic recoil pressure at TLC (Pstat), 13.7+/-0.5 cm H2O vs 11.3+/-0.6 cm H2O (p=0.008); and maximum oxygen consumption, 8.7+/-0.8 mL/min/kg vs 6.9+/-1.5 mL/min/kg (p=0.03). Increase in FEV1 correlated with the increase in TLC Pstat/TLC (r=0.75, p=0.03), but not with any baseline parameter. CONCLUSION: Two years post-LVRS, there is variable clinical and physiologic improvement that does not correlate with any baseline parameter. Increased lung elastic recoil appears to be the primary mechanism for improved airflow limitation.     

Evaluation of emphysema progression as measured by computed tomography in patients with chronic obstructive pulmonary disease

It has been difficult to assess the progression of pulmonary emphysema since accurate quantification of the extent of this condition has only previously been possible on post mortem or resected lungs. Previously we have shown that measurements of CT lung density correlated with the degree of emphysema, measured morphometrically in resected lungs. We have therefore employed this technique to assess the progression of emphysema in 17 patients (12M, 5F) with wide range of chronic airflow limitation (FEV1 15-68% predicted). There was little change in the degree of airflow limitation, hyperinflation or arterial blood gas values over 30 +/- 4 months of follow up (p > 0.05). However during this period there was a significant decrease in the lowest 5th percentile of CT density, which fell from -920 +/- 32 to -940 +/- 36 Hounsfield units (p < 0.005) associated with significant fall in the diffusing capacity for carbon monoxide. We believe that these data show the ability of CT scanning to assess the progression of emphysema in patients with chronic obstructive pulmonary disease.     

Mechanics of breathing in patients with atrial septal defect

Mechanics of breathing and pulmonary diffusing properties were investigated in 24 adult patients with atrial septal defect. The patients were divided into 3 groups according to mean pulmonary artery pressure: less than 19 mm Hg (group I), 20 to 24 mm Hg (group II), and greater than 25 mm Hg (group III). The only change observed in group I was a marked increase in diffusing capacity. Patients of group II showed not only an increase in diffusing capacity, but also an overt decrease in maximal expiratory flow at all lung volumes and at any given driving pressure. For these two groups, a highly significant inverse correlation was found between changes in diffusing and elastic lung properties (r = -0.71; P less than 0.001). In patients of group III, the expiratory flow remained clearly decreased; furthermore, lung compliance and lung volumes were sharply reduced, airway resistance was elevated, and diffusing capacity was normal. Finally, from group I to group III, the lung elastic recoil became progressively diminished at small lung volumes. These results suggest that an increased pulmonary blood volume induces an increase in diffusing capacity and a slight decrease in lung compliance. Simultaneous existance of high intravascular pressure strengthens the effects of increased pulmonary blood volume on lung mechanics and results in significant abnormalities in the lung mechanical behavior. It is postulated that these effects are due to a competition for space between vessels and airways within the bronchovascular sheaths, with a subsequent compression of small airways.     

Applicability of the single-breath carbon monoxide diffusing capacity in a Norwegian Community Study

The test of single-breath diffusing capacity for carbon monoxide (DLCO) has been widely used in population surveys. However, little is known about the effect of meeting or failing to meet the criteria for acceptability of this test. The American Thoracic Society (ATS) recommends a breathholding time of 9 to 11 s, two measurements within +/- 10% or 3 ml CO(STPD)/min/mm Hg of the average DLCO, and an inspiratory vital capacity (IVC) of at least 90% of the largest previously measured forced vital capacity (FVC) as criteria for this test. The objective of the present study was to examine the extent to which these criteria were met in a community study. To do this, a random sample of 3,740 persons, aged 15 to 70 yr, of the general population of the city of Bergen and 11 surrounding municipalities on the southwest coast of Norway were enrolled in a two-phase cross-sectional study. In the second phase, a stratified sample (n = 1,512) of the respondents to the postal questionnaire used for recruitment for the study (n = 3,370) were invited to a clinical and respiratory physiologic examination that included the DLCO test. The attendance rate was 84% (1,275 of 1,512). In the examination, all subjects were able to maintain a breathholding time of 9 to 11 s, and 98% had two DLCO values within +/- 10% or 3 ml CO(STPD)/min/mm Hg of the average DLCO. The criterion of an IVC of at least 90% of FVC in the two tests was met by 68% of the subjects. Younger age was an independent predictor of failure to meet the required criteria. Thus, only two-thirds of the participants fulfilled all of the ATS criteria for the DLCO test, the main reason for failure being an IVC of less than 90% FVC. This should not necessarily lead to the exclusion from further analysis of those failing to meet this criterion.     

Long-term therapy of alpha 1-antitrypsin-deficiency-associated pulmonary emphysema with human alpha 1-antitrypsin

alpha 1-antitrypsin (alpha 1-AT) deficiency is a genetic disorder characterized by low serum levels of alpha 1-AT and a high risk of pulmonary emphysema at a young age. The resulting surplus of proteases, mainly of neutrophil elastase, can be balanced by i.v. augmentation with alpha 1-AT. However, it is not clear if affected patients benefit from long-term augmentation therapy and no long-term safety data are available. We examined 443 patients with severe alpha 1-AT deficiency and pulmonary emphysema receiving weekly i.v. infusions of 60 mg/kg body weight alpha 1-AT in addition to their regular medication. The progression of the disease was assessed by repeated lung function measurements, particularly the decline in forced expiratory volume in 1 second (delta FEV1). 443 patients with alpha 1-AT deficiency tolerated augmentation therapy well with few adverse reactions. The delta FEV1 in 287 patients with available follow-up data was 57.1 +/- 31.1 ml per year. Stratified for baseline FEV1, the decline was 35.6 +/- 21.3 ml in the 108 patients with an initial FEV1 < 30% and 64.0 +/- 26.4 ml in the 164 with 30% < FEV1 < or = 65% of predicted normal (p = 0.0008). The remaining 15 patients had an initial FEV1 > 65%. Long-term treatment with i.v. alpha 1-antitrypsin in patients with severe alpha 1-Pi deficiency is feasible and safe. The decline in forced expiratory volume in one second is related to the initial forced expiratory volume in one second as in alpha 1-antitrypsin deficient patients not receiving augmentation therapy.     

The assessment of the severity of pulmonary edema by computed tomography. A comparison between high-resolution computed tomography, objective evaluation with density masks and functional tests

The results of high-resolution computed tomography (HRCT) were correlated with those of pulmonary function tests, chest films and CT expiratory density mask values in the evaluation of pulmonary emphysema in 33 symptomatic subjects. Emphysema was quantitated with both subjective and objective measurements. Conventional chest films were useful to diagnose severe emphysema but its actual extent was more reliably evaluated with CT scoring systems. HRCT and density mask correlated well with function tests, but the former method exhibited stronger correlation with carbon monoxide diffusion capacity. The opposite was true for hyperinflation and expiratory obstruction variables. Subjective CT estimates, which are quick and easy to perform, were seen to correspond more specifically to the pathophysiologic derangement and should therefore be used to evaluate the anatomic extent of disease. The functional severity of emphysema correlated only with the overall extent of disease and not with its regional distribution in the upper or lower lungs. Finally, in 4 cases (12.1%) with low CT scores, FEV1 was reduced but diffusion capacity values were normal. In one of these patients HRCT showed signs of bronchiolitis. In fact, small airway disease might be a more critical factor in determining functional impairment than the actual anatomical emphysema.     

Transmission disequilibrium analysis of a triplet repeat within the hKCa3 gene using family trios with schizophrenia

We evaluated the long-term outcome of farmer's lung (FL) patients and matched control farmers using high-resolution computed tomography (HRCT). The study population consisted of 88 FL patients and 83 control farmers, matched by age, sex, and smoking habits. The mean time after the first diagnosed episode of FL was 14 yr. The great majority, 82%, of the studied subjects were nonsmokers. Clinical studies included HRCT, spirometry, and pulmonary diffusing capacity. Emphysema was found significantly more often (23%) in FL patients than in control farmers (7%) (p = 0.006). The presence of emphysema was 18% in nonsmoking and 44% in smoking FL patients, the respective values being 4% and 20% in control farmers. Patients with recurrent attacks of FL tended to have emphysema more often (p = 0. 08) than patients who had experienced only a single attack. Fibrosis was observed in 17% of the FL patients and in 10% of the control farmers (p = 0.2). Miliary changes were found in 12% of the FL patients compared with 4% of the control farmers (p = 0.07). Both emphysematous and fibrotic but not miliary changes correlated significantly with impaired pulmonary function. In conclusion, farmer's lung disease seems to be associated with an increased risk of developing emphysema.     

Salivary gland tumors after childhood radiation treatment for benign conditions of the head and neck: dose-response relationships

In this study the mechanisms were investigated whereby ACE-inhibitors improve pulmonary diffusion for carbon monoxide (DLco) in chronic heart failure. The two subcomponents of DLco are the alveolar-capillary membrane conductance (DM) and the capillary blood volume (VC). Stress failure of the membrane in chronic heart failure provides a mechanism for reduction of DM and, as a consequence, impairment of DLco. In 27 patients with chronic heart failure in NYHA functional class II to III and in 13 age- and sex-matched normal subjects, we evaluated the pulmonary function and determined DM and VC, according to the classic Roughton and Forster method, while they were given placebo, at 48 hours and 8 weeks after starting enalapril treatment (10 mg bid). ACE-inhibition had no effect in controls at both short- and mid-term. In chronic heart failure patients, a reduction in VC (likely consequence of a decrease in capillary pulmonary pressure) was the only change observed at 48 hours. At 8 weeks, DM was greatly increased even when the effective alveolar volume (VA) was accounted for (DM/VA), resulting in a significant improvement in DLco, despite a decrease in VC. The slow onset DM improvement makes it likely that the modulatory effect of ACE-inhibition on the membrane function emerges gradually, suggesting that it is likely dissociated from changes in pulmonary capillary pressure and VC. Thus, derangements of the alveolar-capillary membrane in chronic heart failure increase gas diffusion resistance; ACE-inhibition restores the diffusive properties of the membrane and gas transfer, and protects the lung when the heart is failing.     

Control of early cardiac-specific transcription of Nkx2-5 by a GATA-dependent enhancer

STUDY OBJECTIVE: To determine the impact of preoperative resting hypercapnia on patient outcome after bilateral lung volume reduction surgery (LVRS). METHODS: We prospectively examined morbidity, mortality, quality of life (QOL), and physiologic outcome, including spirometry, gas exchange, and exercise performance in 15 patients with severe emphysema and a resting PaCO2 of > 45 mm Hg (group 1), and compared the results with those from 31 patients with a PaCO2 of < 45 mm Hg (group 2). RESULTS: All preoperative physiologic and QOL indices were more impaired in the hypercapnic patients than in the eucapnic patients. The hypercapnic patients exhibited a lower preoperative FEV1, a lower diffusing capacity of the lung for carbon monoxide, a lower ratio of PaO2 to the fraction of inspired oxygen, a lower 6-min walk distance, and higher oxygen requirements. However, after surgery both groups exhibited improvements in FVC (group 1, p < 0.01; group 2, p < 0.001), FEV1 (group 1, p=0.04; group 2, p < 0.001), total lung capacity (TLC; group 1, p=0.02; group 2, p < 0.001), residual volume (RV; group 1, p=0.002; group 2, p < 0.001), RV/TLC ratio (group 1, p=0.03; group 2, p < 0.001), PaCO2 (group 1, p=0.002; group 2, p=0.02), 6-min walk distance (group 1, p=0.005; group 2, p < 0.001), oxygen consumption at peak exercise (group 1, p=0.02; group 2, p=0.02), total exercise time (group 1, p=0.02; group 2, p=0.02), and the perceived overall QOL scores (group 1, p=0.001; group 2, p < 0.001). However, because the magnitude of improvement was similar in both groups, and the hypercapnic group was more impaired, the spirometry, lung volumes, and 6-min walk distance remained significantly lower post-LVRS in the hypercapnic patients. There was no difference in mortality between the groups (p=0.9). CONCLUSIONS: Patients with moderate to severe resting hypercapnia exhibit significant improvements in spirometry, gas exchange, perceived QOL, and exercise performance after bilateral LVRS. The maximal achievable improvements in postoperative lung function are related to preoperative level of function; however, the magnitude of improvement can be expected to be similar to patients with lower resting PaCO2 levels. Patients should not be excluded from LVRS based solely on the presence of resting hypercapnia. The long-term benefit of LVRS in hypercapnic patient remains to be determined.     

Respiratory symptoms, lung function tests, airway responsiveness, and bronchoalveolar lymphocyte subsets in B-chronic lymphocytic leukemia

A respiratory questionnaire was completed and spirometry, tests for lung volumes, diffusion capacity for CO, and methacholine bronchial challenge were performed in 24 outpatients with B-chronic lymphocytic leukemia (B-CLL), aged 44-79, presenting in different stages of their disease. In 10 patients, bronchoalveolar lavage (BAL) fluid was also obtained. Ten of twenty-four patients had symptoms consistent with chronic bronchitis, unrelated both to smoking history and to the clinical stage. Abnormal values (< 2 SD) were found in 4 patients for total lung capacity (TLC), in 9 for vital capacity (VC), 8 for forced expiratory volume in 1 sec (FEV1), 11 for MEF50, 15 for MEF25 and in 7 for diffusing capacity for carbon monoxide. Seven of nineteen patients had PD20FEV1 at less than 1,600 micrograms of methacholine chloride. There was a significantly negative correlation between white blood cell count and VC (r = 0.41, P < 0.05). A positive correlation was found between PD20FEV1 and FEV1/VC (r = 0.61, P < 0.01). The mean and SEM for BAL cells/ml was 463 (71.8) x 10(3). No leukemic cells but a marked increase in T lymphocytes (32.5 +/- 7.8%) were found in BAL fluid. There were significantly negative correlations between the number of BAL CD3+ T lymphocytes and PD20FEV1 (r = 0.61, P < 0.05), and between the number of BAL CD8+ T lymphocytes and PD20FEV1 (r = 0.84, P < 0.01). In conclusion, patients with B-CLL have a high prevalence of respiratory symptoms, small airway dysfunction and CD8 "alveolitis" related to airway responsiveness; despite the well-known lung interstitial lymphocyte infiltration in B-CLL, leukemic cells are not found in BAL fluid.     

Associations between breathing pattern during submaximal exercise and exercise capacity in patients with pulmonary emphysema

We sought to clarify the factors associated with exercise capacity in patients with pulmonary emphysema. Exercise capacities of 20 men with pulmonary emphysema were evaluated by bicycle ergometery, and the results were used to divide the subjects into two groups: high exercise capacity (n = 10) and low exercise capacity (n = 10). Pulmonary-function tests were done, emphysema scores were computed from CT scans, breathing pattern was recorded during submaximal exercise (up to 20 watts), and index of rapid shallow breathing was computed. Neither FEV1 nor airway resistance differed between the two groups, and patients with lower exercise capacity tended to have lower tidal volumes and higher values of the index of rapid shallow breathing during submaximal exercise. Functional residual capacity measured by body plethysmography and emphysema scores were inversely associated with exercise capacity. We speculate that among patients with pulmonary emphysema and a given degree of airway obstruction, a high functional residual capacity causes breathing during submaxinal exercise to be rapid and shallow, and that this rapid and shallow breathing makes ventilation inefficient, increases the work of breathing, and limits exercise capacity.     

Placental diffusing capacities at varied carbon monoxide tensions

To test the hypothesis that carbon monoxide transfer across the placenta is, in part, a facilitated process, we have looked for evidence of saturation kinetics for carbon monoxide. In eight pregnant ewes, fetal to maternal carbon monoxide transfer was examined in a preparation in which the fetal side of the placenta was perfused with blood. The carboxyhemoglobin concentrations on the fetal side of the placenta were varied from 4.8 to 70% in 23 measurements. At increased carbon monoxide tensions, the transfer from fetus to mother always decreased. The slope of log rate of carbon monoxide transfer vs. log partial pressure gradient across the placenta was significantly different from 1. Placental membrane diffusing capacity was calculated separately from total placental diffusing capacity which includes hemoglobin reaction rates and erythrocyte membrane diffusion. Placental membrane diffusing capacity decreased at increased carbon monoxide tensions. Placental permeability for urea did not change with increasing carbon monoxide tensions. These results are consistent with the hypothesis that carbon monoxide diffusion in the placenta is, in part, carrier mediated.     

CO2--emphysema in laparoscopic surgery. Changes in pulmonary CO2-elimination

We report on two patients with subcutaneous carbon dioxide (CO2) emphysema that developed during laparoscopic surgery with CO2 pneumoperitoneum (PP), in whom pulmonary elimination of CO2 (ECO2, Servo ventilator with integrated CO2 analyzer 930, Siemens) was continuously monitored. Patient 1 was a 61-year-old man with laparoscopic herniotomy. ECO2 immediately before PP was 120 ml/min x m2 and increased rapidly after 45 min PP to a maximum value of 340 ml/min x m2. At that time, minute ventilation had been increased from 7 to 11 l/min and PaCO2 had risen from 35 to 57 mm Hg. At the end of the procedure the patient showed excessive subcutaneous emphysema. Patient 2 was a 71-year-old woman in whom diagnostic laparoscopy was performed for staging of a pancreatic tumor. ECO2 immediately before PP was 140 ml/min x m2, increasing dramatically after 45 min PP to a maximum value of 529 ml/min x m2 (Fig. 1). At that time minute ventilation had been increased from 6.2 to 12.5 l/min and PaCO2 had risen from 40 to 77 mm Hg. PP was terminated and the patient was found to have extreme subcutaneous emphysema. She was mechanically ventilated for a further 40 min to normalize PaCO2 and ECO2. It seems reasonable to suppose that an increase in ECO2 by more than 100% of control during CO2-PP is an early sign of CO2 emphysema. In this situation hypercapnia is potentially life-threatening. Evidently, reabsorption of CO2 from loose connective tissue is far more rapid and effective than CO2 resorption from the peritoneal cavity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of lung volume and DLCO in acute respiratory failure

We have undertaken rebreathing measurements of functional residual capacity (FRC), carbon monoxide diffusing capacity (DLCO), and diffusing coefficient (KCO) during positive pressure ventilation in 15 patients with adult respiratory distress syndrome (ARDS). Measurements of oxygenation (PaO2:FIO2 ratio) and lung injury score (LIS) were also recorded. Eight patients subsequently died (mortality of 53%). There was no significant difference in mean FRC, PaO2:FIO2, or LIS at presentation between survivors and nonsurvivors. However, both DLCO and KCO at presentation were significantly greater in survivors than nonsurvivors. In a separate study of nine patients with less severe lung injury, pulmonary capillary blood volume, derived from values of DLCO measured at two different values of FIO2, correlated with invasive pulmonary vascular resistance (PVR) measurements (r = 0.84, p < 0.01). DLCO measurements can be successfully undertaken in patients being ventilated with acute lung injury and may be a useful, noninvasive method of assessing the pulmonary circulation. The lowest values of DLCO were recorded in patients who subsequently did not survive.