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PubMed1994

Effect of hematocrit on systemic O2 transport in hypoxic and normoxic exercise in rats.

The effect of hematocrit (Hct) on O2 transport in hypoxic [inspired PO2 (PIO2) approximately 70 Torr] and normoxic (PIO2 approximately 145 Torr) exercise was studied in rats acclimatized to 3 wk of PIO2 at approximately 70 Torr (A rats) and in nonacclimatized littermates (NA rats). Isovolumic exchange transfusion of plasma or red blood cells was used to lower Hct in A rats from approximately 60 to 45% and to raise Hct of NA rats from 45 to 60%: Controls were A and NA rats exchange transfused with whole blood at constant Hct. Lowering Hct of A rats lowered the arterial O2 concentration (CaO2) and the arterial-mixed venous O2 difference and increased the maximal cardiac output (Qmax) without changes in maximal O2 uptake (VO2 max) or in the product of Qmax x CaO2, circulatory O2 convection at maximal exercise (TO2 max). Raising Hct in NA rats produced the opposite changes in CaO2, arterial-mixed venous O2 difference, and Qmax, but VO2 max and TO2 max increased significantly, both in hypoxia and normoxia, because of relatively small changes in Qmax. In NA rats, a steeper slope of the line relating VO2 max to calculated mean capillary PO2 at high Hct suggested a higher tissue O2 diffusing capacity with high Hct. For a given Hct and Qmax, systemic arterial pressure was higher in A rats. The data suggest that 1) the effect of Hct on systemic hemodynamics is different in A and NA rats, resulting in different effects on VO2 max; 2) factors in addition to Hct contribute to the high systemic vascular resistance of A rats; and 3) increased diffusive conductance for O2, as well as increased TO2 max, could be responsible for the effect of Hct on VO2 max of NA rats.

Acclimatization↗
PubMed1976

[Assessment of working capacity in a group of subjects affected with obstructive respiratory disease (author's transl)].

Ventilatory function was studied by the authors in 43 subjects affected with obstructive respiratory disease. The research was performed both at rest and during two exercise tests -- 60 and 100 watts, respectively. The subjects were divided into three groups on the basis of tidal volume (at 30 1 ventilation) / vital capacity ratio. It was found that during muscular effort subjects with major impairment of spirometric indexes hypoventilated, whereas the opposite occurred in patients with lesser impairment. Moreover, subjects hyperventilating during muscular work were found to have brandypnea, whereas the opposite occurred in hyperventilating patients. It is suggested that progressing and worsening of obstructive emphysema lead to a relative hypoventilation during muscular work, which is due to an "inability" to increase the frequency of breathing.

Adult↗
PubMed2003

Single-breath diffusing capacity of the lung for carbon monoxide: a predictor of PaO2, maximum work rate, and walking distance in patients with emphysema.

OBJECTIVE: The National Emphysema Treatment Trial (NETT) is a randomized, multicenter, clinical trial comparing two different methods of lung volume reduction surgery plus medical therapy to medical treatment alone in patients with advanced emphysema. The purpose of this article was to use the data obtained from the NETT to assess the ability of the single-breath diffusing capacity of the lung for carbon monoxide (DLCO) to predict the need for supplemental oxygen during rest and exercise, as well as overall exercise capacity. METHODS: One thousand seventy-one patients with a mean (+/- SD) FEV(1) of 0.76 +/- 0.24 L were studied. RESULTS: The mean DLCO was 8.0 +/- 3.1 mL/min/mm Hg (28 +/- 10% of predicted). The mean resting PaO(2) was 64 +/- 10 mm Hg. There was a positive association between DLCO and both resting PaO(2) and the requirement for oxygen during a walk at 1 mile per hour (mph). The odds of requiring supplemental oxygen while walking at 1 mph was nine times greater in patients with a DLCO of < or = 20% of predicted than for patients with a DLCO of > 35% of predicted, after adjusting for age and gender. Eighty four percent of individuals with a DLCO of < or = 20% required supplemental oxygen with low levels of exercise compared to 38% of those with a DLCO of > 35%. CONCLUSION: Our results demonstrated that patients with reduced DLCO, particularly when < or = 20% of predicted, are more likely to have reduced PaO(2) at rest and are more likely to require supplemental oxygen with low levels of activity. Thus, DLCO is useful in evaluating whether supplemental oxygen is required for exercise.

Aged↗
PubMed1981

Interstitial pneumonitis associated with mitomycin C and DTIC: a case report.

A case of interstitial pneumonitis secondary to mitomycin C and DTIC combination therapy in a 58-year-old male with metastatic adenocarcinoma of the rectum is reported. Dry cough and dyspnea, especially on exertion, were presenting symptoms. Arterial blood gas analysis was compatible with severe impairment in pulmonary diffusion capacity. Chest x-ray showed a diffuse increase in interstitial markings in both lung fields consistent with interstitial pneumonia. Histologically, prominence of type I pneumocytes, focal proliferation of type II pneumocytes, and varying degree of fibroblastic proliferation and collagenization within the alveolar septae were observed. The obliteration of alveolar septal vessels due to endothelial edema and/or proliferation of fibroblast-like mesenchymal cells were also noted. Withdrawal of drugs and institution of high dose corticosteroid therapy were followed in rapid improvement in dyspnea and arterial blood gas findings. If diagnosed early, this potentially life threatening complication may respond to such therapy.

Adenocarcinoma↗
PubMed1983

Morphometric estimates of diffusing capacity in lungs fixed under zone II and zone III conditions.

Comparative morphometric estimates of the diffusing capacity (DL) were made in rabbit lungs fixed by vascular perfusion under lower zone II and zone III conditions and in lungs fixed by instillation of fixatives into the airways. Owing to a reduction of both capillary volume and membrane diffusing capacity DL of zone II lungs (0.074 +/- 0.007 (SD) ml . sec-1 . mbar-1). was found to be lower by some 25% than DL of instillation-fixed lungs (0.102 +/- 0.012 (SD) ml . sec-1 . mbar-1). The average value of DL of air-filled zone III lungs, on the other hand, almost matched the DL of instillation-fixed lungs. However, DL is not equal in all regions but increases along the vertical axis of zone III lungs. Hence, the previous conclusion that morphometric estimates of DL in instillation-fixed lungs reflects a structural limit for O2 diffusion, which cannot be reached under physiologic conditions, must be revised.

Animals↗
PubMed1989

Total respiratory resistance and reactance in patients with diffuse interstitial lung disease.

In 54 patients with interstitial lung diseases and no signs of airway obstruction we measured lung volumes, maximal expiratory flows, diffusing capacity (DLCO), total respiratory resistance (Rrs) and reactance (Xrs) between 4 and 26 Hz by means of the forced oscillation technique. In all patients DLCO was less than 75% of the expected value. Patients were classified into two groups depending on total lung capacity (TLC): group A with TLC less than 80% of expected, and group B with TLC of 80% or more. Group A demonstrated a decrease of Xrs especially at low frequencies, with small, not significant changes in Rrs. In the patients in this group with the lowest values of TLC (less than 50%), we observed an increase of Rrs at low frequencies causing a negative frequency dependence of Rrs. In group B no distinct changes of Rrs and Xrs occurred. Canonical correlation analysis between routine lung function data and forced oscillation parameters, showed tight correlations between TLC in absolute value or VC in percent of the predicted value on the one hand and average level of Xrs and average slope of Xrs (and Rrs) vs frequency curves on the other hand. Measurements of lung mechanics in five additional patients and comparison with a model of the respiratory system suggest that the changes of Rrs and Xrs are not explained totally by the observed increase in lung tissue resistance and decrease in lung compliance. The observed changes in Rrs and Xrs are not specific for restrictive lung disorders; similar changes are met also in moderately advanced obstructive diseases.

Adult↗
PubMed1975

[Lung ductances and the determination of lung diffusion capacity in silicosis].

A study of the behaviour of global and partial lung ductances for CO having for aim to value the lung diffusion function in 97 silicotic workers was undertaken by authors. The workers were divided into three groups according to the Cincinnati classification. The mean values of the global ductance for CO let appear a fall in all the groups when comparison is made with the standard values previously registered in a group of normal subjects. The partial ductances have put in evidence a fall in the mean values below the normal values, only for what concerns the alveolar-capillar ductance for groups 2 and 3. The study of partial ductances in bronchitic and non-bronchitic silicotic subjects lets appear in the first ones a fall in the ventilatory and alveolar-capillar ductances,-- and in the second ones an isolated fall in the alveolar-capillar ductance.

Humans↗
PubMed2004

Lung volume reduction surgery in canine model of predominantly upper lobe emphysema: advantages of new surgical system.

OBJECTIVE: Lung volume reduction surgery has been shown to be an effective treatment for selected patients with advanced emphysema. Nevertheless, prolonged air leaks are a significant complication that limits the utility of this procedure. This study evaluated the safety and effectiveness of a novel surgical system designed to minimize this complication. METHODS: In 14 dogs, severe upper lobe emphysema was produced by repeated bronchial instillations of papain administered over an approximate 6-month interval. Pulmonary function testing that included lung volumes and flows was performed at baseline, after emphysema, and at 1 month and 6 months after resection in the surgical group, while at comparable intervals in the nonsurgical group. Seven animals were randomly assigned to a surgical group to test a vacuum-assisted surgical system (VALR Surgical System; Spiration; Redmond, WA) that deploys a compression silicone sleeve over portions of the diseased tissue. The other seven dogs comprised the nonsurgical group. RESULTS: In both groups, emphysema increased total lung capacity (TLC) approximately 125% as compared to baseline. In the surgical group, no air leaks were observed after resection, and TLC significantly decreased at the 1-month and 6-month periods as compared with postemphysema measurements. At necropsy, histologic examination revealed fibrosis of the compressed lung contained within the sleeve and fibrotic encapsulation of the device. Two animals had evidence of localized infection. CONCLUSION: We successfully created a model of predominantly upper lobe emphysema. The vacuum-assisted surgical system provided safe and effective lung reduction without air leak complications and with sustained improvement in pulmonary function over 6 months.

Animals↗
PubMed1994

[Factors contributing to exercise-induced hypoxemia in patients with chronic lung diseases].

Arterial oxygen tension (PaO2) was found to decrease linealy during incremental exercise in patients with chronic lung diseases. The slopes of PaO2 during increasing workload (delta PaO2/delta VO2) in patients with COPD were closely and negatively correlated with diffusing capacity of the lung (DLco). In patients with IPF, the values of delta PaO2/delta VO2 were much higher, and were more strongly correlated with DLco than those in patients with COPD. Therefore, exercise-induced hypoxemia (EIH) was found to be related to three factors: PaO2 at rest, PaO2 slope predicted from %DLco, and exercise workload. The most important factor in EIH in patients with COPD was the decrease in PvO2 during exercise, which was caused by right heart failure and venous admixture. In patients with IPF, EIH was caused by abnormal O2 diffusion during exercise, decreased PvO2, and venous admixture. In conclusion, the factors contributing to EIH depend on the workload, so exercise testing is needed to decide on exercise therapy and O2 therapy in patients with chronic lung diseases.

Aged↗
PubMed1996

Effects of two successive maximal exercise tests on pulmonary gas exchange in athletes.

Pulmonary extravascular water accumulation may be involved in exercise-induced hypoxaemia in highly aerobically trained athletes. We hypothesized that if such an alteration were present in elite athletes performing a maximal exercise test, the impairment of gas exchange would be worse during a second exercise test following the first one. Eight male athletes performed two incremental exercise tests separated by a 30-min recovery period. Pulmonary gas exchange and ventilatory data were measured during exercise tests performed in normoxia. Arterial blood samples were drawn each minute during rest, exercise, and recovery. Pulmonary diffusing capacity for CO (DLCO) was measured at rest, after the first (T1) and the second (T2) test. All the subjects underwent a spirometric test at rest and after T2. Maximal and recovery data for O2 uptake and minute ventilation were not statistically different between T1 and T2. Partial pressure of arterial O2 (PaO2) decreased during both tests but was lower during T2 for rest, 60 W, and 120 W (P < 0.02). Alveolar-arterial difference in partial pressure of O2 (PA-aO2) increased during both the tests but was significantly larger during T2 for rest, 60 W, and 120 W (P < 0.01). The PaO2 and PA-aO2 data at maximal exercise were not significantly different between T1 and T2. Compared to rest, PA-aO2 remained significantly larger during recovery for both T1 and T2 (P < 0.0001). The PA-aO2 during T2 recovery was larger than T1 recovery (P < 0.008). Spirometric data did not change. The DLCO measurements after T1 and T2 were not significantly different from rest. These results showed an alteration of PaO2 and PA-aO2 during T1, which tended to be worse during and after T2; however, these data do not allow us to make a definitive statement as to the cause of the hypoxaemia. Our study confirmed that exhausting exercise caused hypoxaemia. It also demonstrated that the disturbance in pulmonary gas exchange persisted for at least 30 min following the end of the exercise period and became worse during submaximal intensities of the following incremental exercise test.

Adult↗
PubMed1984

[Evaluation of the severity of pulmonary embolism. Value of the measurement of stable carbon monoxide transfer capacity].

A non-invasive and easily repeatable method of pulmonary gas exchange evaluation, using measurements of stable carbon monoxide transfer capacity (DLCO) and alveolar-capillary ductance ( DuaCo ), was compared to a complex, invasive method of pulmonary vascular bed evaluation (pulmonary angiography) in 17 patients during the first 24 hours of pulmonary embolism. DLCO and DuaCo measurements were subsequently repeated in several of the patients during the course of the disease. The study showed that DLCO was lowered in both massive (Walsh's angiographic index 12.9 +/- 1.9) and submassive (Walsh's index 4.1 +/- 1.3) pulmonary embolism, with values of 7.0 +/- 2.5 and 7.0 +/- 1.8 ml/min/mm Hg respectively. It also showed a highly significant correlation between the degree of vascular obstruction, as determined by Walsh's angiographic index, and the reduction of alveolar-capillary gas exchange, as evaluated by DuaCo (r = 0.80; p less than 0.001). A progressive improvement in the pulmonary capillary bed perfused could be suspected from the results of DuaCo monitoring during the course of embolism.

Carbon Monoxide↗
PubMed1988

Clinical, functional and pathological correspondence in early stage idiopathic pulmonary fibrosis: evidence for small airway obstruction 1-2.

We describe the clinical, physiological and pathological features of 23 subjects with early stage idiopathic pulmonary fibrosis. Thirteen subjects who had no symptoms had been fortuitously recruited by a routine chest radiograph, whereas the 10 other subjects complained of dyspnea. Twenty-one subjects showed only light to moderate extent of abnormalities on the chest radiograph. Fourteen subjects had a reduced vital capacity whereas 16 and 17 showed a reduced pulmonary compliance and an increase in lung elastic recoil, respectively. Transfer factor was significantly reduced in 18 subjects. Evidence for significant airway obstruction, mainly located at the peripheral level, was demonstrated by a reduced specific lung conductance and upstream conductance in 13 subjects. Airway obstruction was not associated with smoking habits. Bronchial hyperresponsiveness was noted in 50% of the 18 subjects studied. Although fibrosis was mild to moderate in 15 instances, it was only focal, i.e. at least one zone of normal parenchyma in the lung specimen in 17 subjects. Peribronchial fibrosis was established in 8/11 satisfactory biopsy specimens. Significant correlations were observed between rales, the radiological score, some functional indices and the characteristics of fibrosis. We conclude that small airway obstruction documented by physiological and pathological means is frequent in early stage idiopathic pulmonary fibrosis.

Adult↗
PubMed1986

Lung mechanics, cellularity, and surfactant after prenatal starvation in guinea pigs.

Prenatal starvation in the guinea pig causes reduced pulmonary diffusing capacity and retarded alveolarization among neonates. To study the impact of such starvation on biochemical and mechanical properties of the neonatal lung, pregnant guinea pigs were fed ad libitum throughout gestation or starved with 50% rations during their last trimester. Neonatal body weight was 35% less due to starvation, and dry lung weight, DNA, and protein contents were decreased 26, 36, and 31%, respectively (P less than 0.001 for all). Hematological data indicated no anemia, hypoproteinemia, or altered glucocorticoid levels due to starvation. Total surfactant phospholipids in these neonates were reduced 61% in lavage and 35% in the neonatal lung tissue, although surfactant compositions were similar to controls. Specific lung compliance in the air-filled lungs was not altered, but the saline-filled lungs were more distensible over deflation pressures of 9-18 cmH2O (transpulmonary). Although starvation retarded both lung cellularity and surfactant, only that portion of lung elastic recoil attributable to tissue forces was affected.

Animals↗
PubMed2006

Sustained low diffusing capacity in hepatopulmonary syndrome after liver transplantation.

AIM: To study the presence of sustained low diffusing capacity (DL(CO)) after liver transplantation (LT) in patients with hepatopulmonary syndrome (HPS). METHODS: Six patients with mild-to-severe HPS and 24 without HPS who underwent LT were prospectively followed before and after LT at mid-term (median, 15 mo). HPS patients were also assessed at long-tem (median, 86 mo). RESULTS: Before LT, HPS patients showed lower PaO(2) (71 +/- 8 mmHg), higher AaPO(2) (43 +/- 10 mmHg) and lower DL(CO) (54% +/- 9% predicted), due to a combination of moderate-to-severe ventilation-perfusion (V(A)/Q) imbalance, mild shunt and diffusion limitation, than non-HPS patients (94 +/- 4 mmHg and 19 +/- 3 mmHg, and 85% +/- 3% predicted, respectively) (P<0.05 each). Seven non-HPS patients had also reduced DL(CO) (70% +/- 4% predicted). At mid- and long-term after LT, compared to pre-LT, HPS patients normalized PaO(2) (91 +/- 3 mmHg and 87 +/- 5 mmHg), AaPO(2) (14 +/- 3 mmHg and 23 +/- 5 mmHg) and all V(A)/Q descriptors (P<0.05 each) without changes in DL(CO) (53% +/- 8% and 56% +/- 7% predicted, respectively). Post-LT DL(CO) in non-HPS patients with pre-LT low DL(CO) was unchanged (75% +/- 6% predicted). CONCLUSION: While complete V(A)/Q resolution in HPS indicates a reversible functional disturbance, sustained low DL(CO) after LT also present in some non-HPS patients, points to persistence of sub-clinical liver-induced pulmonary vascular changes.

Adult↗
PubMed1988

Longitudinal mixing in dog lungs during high-frequency forced flow oscillation.

Longitudinal mixing in the conducting airways of eight intubated anesthetized beagles (10.8 +/- 0.9 kg) was studied at functional residual capacity in the presence of forced sinusoidal flow oscillations and in the absence of fresh air bias flow. The ranges of oscillation conditions were: frequencies, f, from 3 to 18 Hz and minute volumes, Vosc, from 50 to 150 ml/sec, corresponding to tidal volumes, Vosc/f, from 0.3 to 4.5 ml/kg body mass. Oscillations were imposed during a breath holding interval incorporated into a modified single-breath nitrogen (N2) washout maneuver. The expired N2 fraction curves were analyzed with a Fickian diffusion model by adjusting the value of a global mixing parameter, (DA2), to achieve an optimal fit of the model to the data. The mixing parameter was an increasing function of minute volume and a decreasing function of frequency, which is well represented by the equation: (DA2) = 2.72 Vosc 1.74 f-1.57 By comparison to available theory and previous measurements in physical systems, this formula implies that Taylor-type dispersion is the dominant mixing mechanism in the conducting airways. Also, the diffusion model predicted, and the data verified, the existence of a mouth-ward 'diffusion flow' during breath holding. This effect, caused by the non-uniform nature of the summed airway cross-section, is directly correlated with the value of (DA2).

Animals↗
PubMed1985

Effect of breath-hold time on DLCO(SB) in patients with airway obstruction.

The single-breath diffusing capacity of the lung for CO [DLCO(SB)] is considered a measure of the conductance of CO across the alveolar-capillary membrane and its binding with hemoglobin. Although incomplete mixing of inspired gas with alveolar gas could theoretically influence overall diffusion, conventional calculations of DLCO(SB) spuriously overestimate DLCO(SB) during short breath-holding periods when incomplete mixing of gas within the lung might have the greatest effect. Using the three-equation method to calculate DLCO(SB) which analytically accounts for changes in breath-hold time, we found that DLCO(SB) did not change with breath-hold time in control subjects but increased with increasing breath-hold time in both patients with asthma and patients with emphysema. The increase in DLCO(SB) with increasing breath-hold time correlated with the phase III slope of the single-breath N2 washout curve. We suggest that in patients with ventilation maldistribution, DLCO(SB) may be decreased for the shorter breath-hold maneuvers because overall diffusion is limited by the reduced transport of CO from the inspired gas through the alveolar gas prior to alveolar-capillary gas exchange.

Adult↗
PubMed1997

Effect of alveolar volume on the interpretation of single breath DLCO.

Single-breath carbon monoxide diffusing capacity in the whole lung (DLCO) and per unit alveolar volume (DLCO/VA), as expressed in percentage of normal values, gave discordant results when VA of the patients was abnormal. It was hypothesized that normal reference values were inappropriate to interpret data collected in such patients. To substantiate this hypothesis, DLCO and DLCO/VA were measured in four groups: (1) normal volunteers in whom both indices were measured at five different VA; (2) patients with high VA; (3) emphysematous patients; and (4) patients with diffuse interstitial lung diseases (DILD). In normal subjects, DLCO increased and DLCO/VA decreased with VA. In patients with overinflated lungs, the percentage of DLCO was more increased than DLCO/VA. In the emphysematous patients, both indices were equally decreased. In patients with DILD, DLCO was significantly more decreased than DLCO/VA in those suffering from a restrictive pattern. Theoretical values were re-calculated taking into account their true VA and using the relationships observed between DLCO, DLCO/VA and VA. The divergences between DLCO and DLCO/VA were strongly minimized. Therefore, the authors suggest the need to correct theoretical formulas in the presence of a restrictive pattern.

Adult↗