Search PubMed⌕ Search

Biomedical subjects

W MacNee

Publications and source records attributed to W MacNee.

At least 109 records · Page 6Linked to original sources
PubMed1994

Erythrocyte and polymorphonuclear cell transit time and concentration in human pulmonary capillaries.

Pulmonary capillary transit times were examined in patients who required lung resection by use of 99mTc-labeled macroaggregates (99Tc-MAA) and chromium-labeled erythrocytes (51Cr-RBC) to measure regional blood flow and volume in the resected lung. Cell flow (cells.ml-1.s-1) to each resected lung sample was determined by multiplying the number of polymorphonuclear leukocytes (PMN) per milliliter of circulating blood by the blood flow to that sample. Capillary blood volume was obtained by multiplying the morphometrically determined fraction of pulmonary blood in capillaries by the total 51Cr-RBC volume in each sample. Cell concentrations (cells/ml) in capillary blood were calculated morphometrically, and capillary transit times were obtained by dividing cell concentration by cell flow. The results show that PMN transit times were 60-100 times longer than the RBC transit times, with a 22% overlap between their distributions. We conclude that PMN are concentrated with respect to RBC in pulmonary capillary blood because of differences in their transit times and that these long transit times provide an opportunity for PMN-endothelial interactions.

Blood Flow Velocity↗
PubMed1994

Rheological response of neutrophils to different types of stimulation.

The potential for neutrophils to obstruct microvessels was evaluated by measuring transit of individual neutrophils through 8-microns pores in an automated cell transit analyzer (CTA) or into micropipettes (4-8 microns ID). Stimulation in vitro by the chemotactic agent N-formyl-methionyl-leucyl-phenylalanine. (fMLP), cigarette smoke, or purified antineutrophil cytoplasm antibodies greatly increased flow resistance, but the response varied in its dependence on time and pore diameter. Cigarette smoke or fMLP caused rapid loss of cellular deformability, although observations were complicated by changes in cell shape: progressive bipolar shape formation (after treatment with fMLP) could facilitate entry into larger pores (approximately 8 microns), whereas blebs induced by cigarette smoke caused bridging of these pores with cell immobilization. These processes led to an underestimation of the changes in deformability by the CTA. Neutrophils responded slowly to the antineutrophil cytoplasm antibodies (approximately 30 min), with a greater increase in flow resistance evaluated by a micro-pipette (4-6 microns ID) than by the CTA. We conclude that the effect of neutrophil stimulation on flow through capillary-sized vessels is potentially great (with resistance typically increased 10-fold or even complete blockage) but may depend on the vascular and cellular geometry and may be local or disseminated, depending on the rate of the rheological response.

Adult↗
PubMed1994

An investigation of the role of glutathione in increased epithelial permeability induced by cigarette smoke in vivo and in vitro.

Airspace epithelial permeability is known to increase in cigarette smokers. To study the role of the antioxidant reduced glutathione (GSH) in this phenomenon, we used an in vitro model of the epithelial permeability of a monolayer of human type II alveolar epithelial cells (A549 cell line). Both whole (WSC) and vapor (VSC) smoke condensates induced a recoverable, concentration-dependent increase in epithelial permeability to 125iodine-labeled bovine serum albumin (125IBSA), associated with a profound fall in intracellular GSH. Buthionine sulfoximine (BSO), a GSH synthesis inhibitor, decreased GSH levels in A549 epithelial cells, significantly increased A549 epithelial cell permeability, and enhanced both WSC and VSC-induced A549 epithelial cell permeability. Co-culturing epithelial cells and GSH (500 microM) reduced WSC-induced, but not VSC-induced A549 epithelial cell permeability. Increasing intracellular GSH also ameliorated the smoke-induced increased epithelial permeability. Concentrations of cigarette smoke condensate of < 20% increased A549 epithelial cell permeability without associated cell detachment and lysis, which was also the case with BSO-induced increased epithelial permeability. WSC and VSC, instilled intratracheally, significantly increased rat lung epithelial permeability to 125IBSA, 6 h postinstillation, associated with a significant recruitment of neutrophils into the airspaces. This was associated with a small increase in GSH in the lung tissue of VSC-treated rats. However, both WSC and VSC markedly reduced GSH in bronchoalveolar lavage (BAL) fluid. Reduction in lung GSH to 95% but not to 68% of control values by BSO increased lung epithelial permeability in vivo. However, there was no additive effect on epithelial permeability of WSC and BSO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Neutrophil sequestration in lungs removed at surgery. The effect of microscopic emphysema.

Neutrophils within the lungs are considered to play an important role in the pathogenesis of pulmonary emphysema. We have studied the intravascular distribution of reinjected autologous 111In-labeled neutrophils in lung specimens resected 10 min after reinjection from 10 patients undergoing surgery for peripheral bronchogenic tumors. An excess of neutrophils relative to that expected for the 99mTc-labeled erythrocyte blood volume was confirmed in all specimens (range, 3- to 136-fold). In seven specimens which were completely examined, this excess displayed a skewed distribution, with a median neutrophil sequestration of 20-fold excess, and correlated with local blood volume (r = -0.51; p < 0.001). There was also a significant correlation between alveolar wall surface area per unit volume of lung (AWUV) and neutrophil excess, when randomly selected tissue blocks from each specimen were analyzed (r = 0.34, n = 51, p = 0.012). This same trend was demonstrated when whole specimen median values were considered (r = 0.64, n = 7, p = 0.07). Thus in areas of the lungs with lower AWUV values (increasing microscopic emphysema), fewer neutrophils were present. These studies add further support to the view that emphysema per se is not associated with an increased sequestration of pulmonary intravascular neutrophils.

Aged↗
PubMed1993

Parenchymal emphysema measured by CT lung density correlates with lung function in patients with bullous disease.

In subjects with chronic obstructive pulmonary disease (COPD) computed tomographic (CT) lung density correlates with direct pathological measurements of the size of the distal airspaces, as well as with measurements of airflow limitation and impairment of the diffusing capacity. Thus, CT lung density can be used to quantify emphysema in life. We wanted to assess the use of CT scanning to detect and measure the extent of bullous lung, and to quantify the severity of emphysema in the non-bullous areas of the lungs. In patients with bullous emphysema (21 males and 2 females; aged 31-69 yrs; forced expiratory volume in one second (FEV1) 14-84% predicted; volume corrected diffusing capacity of the lungs for carbon monoxide (DLCO/VA) 17-114% predicted). CT lung density was measured in electromagnetic imaging (EMI) units. The extent of bullous emphysema correlated poorly with all respiratory function measurements. In contrast, the severity of emphysema in the non-bullous parts of the lungs, expressed as either the mean EMI number, or the EMI number of the lowest 5th percentile of the CT lung density histogram, correlated well with measurements of airflow limitation and diffusing capacity. Our findings, thus, suggest that in patients with bullae the major determinant of respiratory function is the severity of the emphysema in non-bullous lung, and that the extent of the bullae has less functional importance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Relation between distal airspace size, bronchiolar attachments, and lung function.

BACKGROUND--Smoking related fixed airway obstruction may be due to airway scarring and narrowing or decreased support due to loss of adjacent alveolar walls. In this study of resected specimens, preoperative pulmonary function was compared with results of a morphometric study of lung structure. METHODS--Morphometric measurements were made on 42 inflation fixed lung specimens as follows: airspace wall surface area per unit volume (AWUV) was measured on at least 25 l mm2 histological fields from each specimen, expressed as a mean, and the mean of the lowest five measurements for each case (LF5). Minimum diameter, maximum diameter, diameter ratio (ellipticality), lumen area, and lumen circumference were measured on at least 16 non-respiratory bronchioles from each lung. Peribronchiolar alveolar support was measured as mean interalveolar attachment distance (IAAD). Measurements of pulmonary function included forced expiratory volume in one second (FEV1) (absolute and % predicted values; n = 42), slope of phase III (single breath nitrogen test; n = 28), closing volume (expressed as a percentage of vital capacity (CV/VC%); n = 28). RESULTS--Bronchiolar size was not independently related to the tests of lung function used. Percentage predicted FEV1 was related to mean IAAD, ellipticality, and mean AWUV. CV/VC% showed significant relation with ellipticality, mean AWUV, and LF5 AWUV. Slope of phase III increased with increasing IAAD. Significant correlations were found between ellipticality and AWUV (mean and LF5), and between ellipticality and IAAD. Both IAAD and ellipticality were significantly increased in patients with abnormally low FEV1. CONCLUSION--Destruction of airspace walls, particularly those attached to the peripheral bronchioles, is more influential in determining airflow limitation than bronchiolar size.

Aged↗
PubMed1993

Atrial natriuretic peptide in stable and decompensated chronic obstructive pulmonary disease.

BACKGROUND: Plasma levels of atrial natriuretic peptide (ANP) are elevated in patients with chronic obstructive pulmonary disease (COPD) and may have a role in preventing oedema formation in these patients. METHODS: Plasma ANP levels were measured in 60 patients with COPD and these measurements were related to pulmonary haemodynamics, response to treatment during exacerbations, and clinical patterns of the stable disease. RESULTS: Plasma ANP levels did not correlate significantly with right atrial or pulmonary arterial pressures but did correlate significantly with both the right ventricular end diastolic volume and right ventricular wall volume measured by magnetic resonance imaging. Oxygen (2 1/min by nasal prongs for 30 minutes) did not change the mean pulmonary arterial pressure or the level of plasma ANP. In 20 patients with an acute exacerbation of COPD plasma ANP levels were higher in those with oedema (302 (185) pg/ml) than in those without oedema (87 (43) pg/ml). Oxygen given for one hour had no effect on plasma levels of ANP. However, plasma ANP levels fell over the first three days during treatment in those with oedema, the fall correlating with the change in body weight. In a further 20 stable patients with hypoxic COPD, those with hypercapnia and previous episodes of oedema had higher levels of plasma ANP (120 (50) pg/ml) than normocapnic patients with no previous oedema (54 (15) pg/ml). CONCLUSIONS: The level of ANP is high in the plasma of patients with COPD, particularly during exacerbations in those with oedema. The association of a high plasma ANP level and volume overload is shown by the fall in ANP levels with treatment of the oedema, and the correlation between levels of ANP and right ventricular end diastolic or wall volumes.

Acute Disease↗
PubMed1993

Decreased leukocyte deformability after acute cigarette smoking in humans.

Acute cigarette smoking increases the sequestration of neutrophils in the lungs of humans. This may be due to the delayed transit of cells in the pulmonary microcirculation, which may result from a reduction in cell deformability as suggested by in vitro studies of smoke-exposed neutrophils. In order to support this hypothesis we wished to determine if a reduction in leukocyte deformability could be measured in whole blood exposed to smoke in vitro or in vivo. Whole blood filterability, which largely reflects leukocyte deformability, was measured as the pressure developed by filtration of diluted whole blood through a micropore membrane. Whole blood filtration pressures did not change when blood was exposed to smoke in vitro or in venous blood after acute smoking in vivo. However, arterial blood sampled from chronic smokers during acute smoking showed a consistent reduction in leukocyte deformability associated with a small increase in plasma elastase. To assess whether these changes were induced by oxidants in cigarette smoke, we measured the levels of the antioxidant glutathione (GSH), erythrocyte (RBC) membrane fragility, and products of lipid peroxidation in plasma and RBC in blood exposed to smoke in vivo and in vitro. No change in RBC lipid peroxidation or membrane fragility could be detected after in vitro smoke exposure, possibly because of the high antioxidant capacity of the RBC. However, reduced blood GSH levels and increased levels of lipid peroxidation products were detected in plasma, reflecting oxidant stress. In contrast, we were unable to detect evidence of an increased oxidant burden in blood after acute smoking in vivo, in either arterial or venous blood samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The effects of cigarette smoking on pulmonary hemodynamics.

Neutrophils are delayed in transit in the pulmonary circulation during smoking which could reflect smoke-induced changes in local hemodynamics. The purpose of this study was to measure the changes in pulmonary hemodynamics during cigarette smoking in both healthy smokers and patients with COPD with and without pulmonary hypertension. In eight healthy smokers, cigarette smoking decreased the transit time of technetium-99m-labeled red blood cells, associated with an increase in cardiac output and a fall in the pulmonary blood volume index. In patients with COPD, the cardiac index also increased during smoking associated with a small increase in pulmonary arterial pressure only in those patients with pulmonary hypertension. However, pulmonary vascular resistance fell. These changes in pulmonary hemodynamics during cigarette smoking could not account for the increased neutrophil sequestration that has been observed previously in the lungs during smoking.

Adult↗
PubMed1992

Microscopic and macroscopic measurements of emphysema: relation to carbon monoxide gas transfer.

BACKGROUND: Studies of the relation between the severity of structural change in emphysema and physiological abnormality have been based on macroscopic assessments, which have not been truly quantitative or sensitive enough to detect early changes. With a highly reproducible method for measuring emphysema using histological sections and a semiautomatic image analysis system, this quantitative assessment of emphysema was compared with a semiquantitative macroscopic assessment of emphysema and measurements of carbon monoxide gas transfer. METHODS: Microscopic and macroscopic measurements of emphysema on 44 thoracotomy specimens were compared; only two were from non-smokers. Airspace wall surface area per unit volume was measured microscopically with an automatic image analyser and expressed as both the mean airspace wall surface area per unit volume and the mean value of the five fields with the lowest values. Macroscopic emphysema was measured directly on a tracing of the midsagittal slice using a digitising tablet attached to a microcomputer and expressed as a percentage of the total area of lung. In cases with centriacinar emphysema the number of discrete lesions was counted. RESULTS: The area of macroscopic emphysema ranged from 0 to 78% of the total area of lung examined, but most patients had less than 1% involvement so that the distribution was highly skewed. Both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume were normally distributed, with mean airspace areas ranging from 8.8 to 25.4 mm2/mm3 (mean 18.1 mm2/mm3). In lobes with centriacinar emphysema the number of discrete lesions correlated with airspace wall surface area per unit volume and with preoperative carbon monoxide transfer factor (TLCO) per unit lung volume. However, other measurements of macroscopic emphysema did not correlate with loss of alveolar wall surface area, and there was considerable overlap between subjects with no or minimal macroscopic emphysema and those with more severe disease. TLCO correlated with both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume but not with the severity of macroscopic emphysema. CONCLUSION: If emphysema is to be quantified it must be measured microscopically; macroscopic measurements do not, in general, reflect the microscopic loss of airspace wall.

Aged↗
PubMed1992

Hemodynamic effects of ibopamine on the pulmonary circulation and right ventricular performance in patients with chronic obstructive pulmonary disease.

We have studied the effects of ibopamine, an oral dopamine derivative, on pulmonary hemodynamics and blood gas values when given as a single oral dose (100 mg) to patients with severe hypoxic chronic obstructive pulmonary disease. A small but significant increase in mean pulmonary arterial pressure from 29 +/- 8 to 32 +/- 7 mm Hg (p < 0.01) was noted 30 min after ibopamine was given associated with a small increase in cardiac index. No other consistent hemodynamic changes were observed, and no alteration in blood gas values or oxygen saturation occurred. These results do not indicate a role for ibopamine in the treatment of patients with hypoxic chronic obstructive pulmonary disease and pulmonary hypertension, but, in addition, do not indicate any major deleterious effects of ibopamine on pulmonary hemodynamics or blood gas values in such patients.

Administration, Oral↗
PubMed1992

Predictors of survival in patients treated with long-term oxygen therapy.

Long-term oxygen therapy (LTOT) has been shown in two controlled trials to improve survival in patients with hypoxic chronic obstructive pulmonary disease. The cause of this improved survival is unknown and was best correlated in the Medical Research Council (MRC) trial with the sum of the PaCO2 and the red cell mass. However, the survival curves of treated and untreated patients in the MRC trial for males were not significant until greater than 500 days of treatment. This suggests that some patients derive little benefit from LTOT. Follow-up data from the National Institutes of Health (NIH) trial indicate that pulmonary haemodynamics, including pulmonary vascular resistance, predict survival in such patients. In a previous study in 115 randomly selected patients with chronic obstructive pulmonary disease (COPD) who were not treated with LTOT, we found that PaO2 and PaCO2, measured when breathing air, were more significant predictors of survival than the presence of cor pulmonale or right ventricular function. We have also compared a group of 154 patients treated with LTOT in two centres, in Warsaw and Edinburgh, where criteria for patient selection for LTOT and subsequent survival curves were very similar in both centres. A pulmonary arterial pressure of greater than 29 mm Hg and a PaO2 when breathing air of less than 7.0 kPa produced a significant decrease in survival using a Cox survival model. These results suggest that patients with more severe COPD may not benefit from LTOT. Other factors such as poor compliance with treatment, lack of adequate oxygenation and increasing age of patients prescribed LTOT may also contribute to the reduced benefit from this treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Changes in neutrophil deformability following in vitro smoke exposure: mechanism and protection.

We have previously demonstrated a reduction in the deformability of neutrophils, exposed to whole particulate cigarette smoke in vitro, by measuring their ability to filter through a micropore membrane with pore dimensions similar to those of the average pulmonary capillary segment. In this study, we exposed neutrophils to the vapor phase of cigarette smoke and investigated the mechanism of the reduction in neutrophil filterability. Although both stimulated neutrophils and smoke-exposed neutrophils demonstrated an increase in filtration pressures, and thus a reduction in cell deformability, compared with control untreated cells, the spontaneous release of the reactive oxygen intermediates hydrogen peroxide and the superoxide anion was depressed following in vitro smoke exposure and there was no shape change to suggest that smoke-exposed cells were activated. The presence of erythrocytes, plasma, or the antioxidants albumin and glutathione prevented the reduction in cell filterability following smoke exposure, suggesting that in vitro smoke exposure, in our system, was mediated by oxidants. Indeed, the increase in filtration pressures, produced by smoke, could be mimicked by the addition of the oxidant hypochlorous acid. The cytoskeletal inhibitors cytochalasin B and D improved the filterability of smoke-exposed cells, suggesting that smoke may change neutrophil deformability through an effect on the actin component of the cytoskeleton. By contrast, colchicine, a specific inhibitor of the microtubules, had no effect. Preincubation with a monoclonal antibody to the CD18 antigen, to block this major neutrophil adhesive glycoprotein, did not alter the filtration pressure developed by stimulated or smoke-exposed neutrophils, suggesting that increased adhesivity was not the mechanism of the increase in filtration pressures observed following smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Antioxidants↗