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Biomedical subjects

E M Wagner

Publications and source records attributed to E M Wagner.

At least 19 recordsLinked to original sources
PubMed1997

Effect of lung inflation in vivo on airways with smooth muscle tone or edema.

Fibrous attachments to the airway wall and a subpleural surrounding pressure can create an external load against which airway smooth muscle must contract. A decrease in this load has been proposed as a possible cause of increased airway narrowing in asthmatic individuals. To study the interaction between the airways and the surrounding lung parenchyma, we investigated the effect of lung inflation on relaxed airways, airways contracted with methacholine, and airways made edematous by infusion of bradykinin into the bronchial artery. Measurements were made in anesthetized sheep by using high-resolution computed tomography to visualize changes in individual airways. During methacholine infusion, airway area was decreased but increased minimally with increases in transpulmonary pressure. Bradykinin infusion caused a 50% increase in airway wall area and an small decrease in airway luminal area. In contrast to airways contracted with methacholine, the luminal area after bradykinin increased substantially with increases in transpulmonary pressure, reaching 99% of the relaxed area at total lung capacity. Thus airway edema by itself did not prevent full distension of the airway at lung volumes approaching total lung capacity. Therefore, we speculate that if a deep inspiration fails to relieve airway narrowing in vivo, this must be a manifestation of airway smooth muscle contraction and not airway wall edema.

Animals↗
PubMed1997

Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo.

Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo. J. Appl. Physiol. 83(2): 366-370, 1997.-Inflammatory changes and airway wall thickening are suggested to cause increased airway responsiveness in patients with asthma. In five sheep, the dose-response relationships of individual airways were measured at different lung volumes to methacholine (MCh) before and after wall thickening caused by the inflammatory mediator bradykinin via the bronchial artery. At 4 cmH2O transpulmonary pressure (Ptp), 5 microg/ml MCh constricted the airways to a maximum of 18 +/- 3%. At 30 cmH2O Ptp, MCh resulted in less constriction (to 31 +/- 5%). Bradykinin increased airway wall area at 4 and 30 cmH2O Ptp (159 +/- 6 and 152 +/- 4%, respectively; P < 0.0001). At 4 cmH2O Ptp, bradykinin decreased airway luminal area (13 +/- 2%; P < 0.01), and the dose-response curve was significantly lower (P = 0.02). At 30 cmH2O, postbradykinin, the maximal airway narrowing was not significantly different (26 +/- 5%; P = 0.76). Bradykinin produced substantial airway wall thickening and slight potentiation of the MCh-induced airway constriction at low lung volume. At high lung volume, bradykinin increased wall thickness but had no effect on the MCh-induced airway constriction. We conclude that inflammatory fluid leakage in the airways cannot be a primary cause of airway hyperresponsiveness.

Animals↗
PubMed1997

Effects of edema on small airway narrowing.

Numerous mediators of inflammation have been demonstrated to cause airway microvascular fluid and protein extravasation. That fluid extravasation results in airway wall edema leading to airway narrowing and enhanced reactivity has not been confirmed. In anesthetized, ventilated sheep (n = 30), airway vascular fluid extravasation was induced by infusing bradykinin (10(-6) M) through a cannulated, blood-perfused bronchial artery. Airway wall edema and luminal narrowing were determined morphometrically. Airway reactivity to methacholine (MCh; 10 microg/ml, intrabronchial artery) was determined by measuring conducting airway resistance (Raw) by forced oscillation. Raw measurements were made and lung lobes were excised and quick frozen before or after a 1-h bradykinin infusion. In 10 airways per lobe (range 0.2- to 2.0-mm relaxed diameter), wall area occupied 32 +/- 2% (SE) of the total normalized airway area (n = 9). Bradykinin infusion increased wall area to 42 +/- 5% (P = 0.02); luminal area decreased by <5%; and smooth muscle perimeter, a measure of smooth muscle constriction, was not altered (n = 5). Raw showed no change from baseline (1.4 +/- 0.4 cmH2O . l-1 . s) after bradykinin infusion (n = 10). During MCh challenge, Raw increased by 3.2 +/- 04 cmH2O . l-1 . s, and this change did not differ after administration of bradykinin. MCh challenge caused similar decreases in smooth muscle perimeter (10%) and luminal area (72 vs. 68%) before and after bradykinin infusion. However, the time constant of recovery of Raw from MCh constriction was increased from control (40 +/- 3 s) to 57 +/- 10 s after bradykinin infusion (P = 0.03). When lung lobes were excised at the same time after MCh challenge was terminated (n = 5), luminal area was greater before bradykinin infusion than after (86 vs. 78%; P = 0.007), as was smooth muscle perimeter. The results of this study demonstrate that airway wall edema limits relaxation after induced constriction rather than enhancing constriction.

Airway Resistance↗
PubMed1997

[Bottle feeding].

Explore the source record for details and available documents.

Bottle Feeding↗
PubMed1996

Career development for women in academic medicine: Multiple interventions in a department of medicine.

OBJECTIVE: To determine the gender-based career obstacles for women in an academic department of medicine and to report the interventions to correct such obstacles (resulting from the evaluation) and the results of these interventions. DESIGN: Intervention study, before-after trial, with assessment of faculty concerns and perceived change through structured, self-administered questionnaires. SETTING: The Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md. PARTICIPANTS: Full-time faculty. INTERVENTIONS: Multifaceted intervention from 1990 through 1995 to correct gender-based career obstacles reported by women faculty, including problem identification, leadership, and education of faculty, and interventions to improve faculty development, mentoring, and rewards and to reduce isolation and structural career impediments. MAIN OUTCOME MEASURES: Retention and promotion of deserving women faculty, salary equity, quality of mentoring, decreased isolation from information and colleagues, integration of women faculty into the scientific community, and decreased manifestations of gender bias. RESULTS: Junior women were retained and promoted, reversing previous experience, with a 550% increase in the number of women at the associate professor rank over 5 years (from 4 in 1990 to 26 in 1995). Interim 3-year follow-up showed a 183% increase in the proportion of women faculty who expected they would still be in academic medicine in 10 years (from 23% [7/30] in 1990 to 65% [30/46] in 1993). One half to two thirds of women faculty reported improvements in timeliness of promotions, manifestations of gender bias, access to information needed for faculty development, isolation, and salary equity. Men also reported improvements in these areas. CONCLUSIONS: The outcomes reported here indicate that it is possible to make substantive improvements in the development of women's careers, that an institutional strategy to this end can be successful in retaining women in academic medicine, and that such interventions are likely to benefit all faculty. Long-term interventions appear essential.

Academic Medical Centers↗
PubMed1996

Effects of bronchial vascular engorgement on airway dimensions.

Airway vascular engorgement has been suggested to cause luminal narrowing and airflow obstruction. To determine the extent to which changes in bronchial vascular volume could influence airway dimensions, we studied the effects of left atrial pressure elevation on airway morphometry in sheep (n = 17). The bronchial branch of the bronchoesophageal artery was cannulated and perfused with autologous blood (0.6 ml.min-1.kg-1). A balloon-tipped catheter was inserted into the left atrial appendage to elevate left atrial pressure by 10 mmHg, and papaverine was infused into the bronchial artery to eliminate airway smooth muscle tone. Morphological measurements were made from rapidly frozen lungs excised in vivo. Left atrial pressure elevation caused a 79% increase in total vascular area (P = 0.0002). Average airway luminal area was significantly decreased from 86 to 71% of the airway maximal area (P < 0.0001). Noteworthy were the prominent bronchial vessels located within mucosal folds. However, when papaverine was infused during left atrial pressure elevation, despite a comparable total vascular area, luminal narrowing did not occur and remained at 87% of the maximal area (P = 0.6267). In conclusion, we found that engorgement of the bronchial vasculature leads to an increase in the vascular area in regions inside and outside the smooth muscle layer. The associated decrease in luminal area only occurs in the presence of airway smooth muscle tone. This suggests a reflex effect on the airway caused by the vascular engorgement. We conclude that vascular engorgement of the airway wall per se has a negligible effect on airway obstruction.

Airway Resistance↗
PubMed1996

Importance of airway blood flow on particle clearance from the lung.

The role of the airway circulation in supporting mucociliary function has been essentially unstudied. We evaluated the airway clearance of inert, insoluble particles in anesthetized ventilated sheep (n = 8), in which bronchial perfusion was controlled, to determine whether airway mucosal blood flow is essential for maintaining surface transport of particles through airways. The bronchial branch of the bronchoesophageal artery was cannulated and perfused with autologous blood at control flow (0.6 ml.min-1.kg-1) or perfusion was stopped. With the sheep in a supine position and after a steady-state 133Xe ventilation scan for designation of lung zones of interest, an inert 99mTc-labeled sulfur colloid aerosol (2.1-microns diameter) was deposited in the lung. The clearance kinetics of the radiolabeled particles were determined from the activity-time data obtained for right and left lung zones. At 60 min postdeposition of aerosol, average airway particle retention for control bronchial blood flow conditions was 57 +/- 7 (SE)% for the right and 53 +/- 8% for the left lung zones. Clearance of particles was significantly impaired when bronchial blood flow was stopped, e.g., right and left lung zones averaged 77 +/- 6 and 76 +/- 7% at 60 min, respectively (P < 0.05). These data demonstrate a significant influence of the bronchial circulation on mucociliary transport of insoluble particles. Potential mechanisms that may account for these results include the importance of the bronchial circulation for nutrient flow, maintenance of airway wall temperature and humidity, and release of mediators and sequelae associated with tissue ischemia.

Aerosols↗
PubMed1996

Dissociation of bradykinin-induced plasma exudation and reactivity in the peripheral airways.

To determine if bradykinin, a potential mediator of asthma, acts, at least in part, at the level of the peripheral airways, we used a wedged bronchoscope technique to study asthmatic and normal subjects. Baseline peripheral airways resistance (Rp) was measured in the right upper lobe. Subjects then received saline, followed by increasing doses of bradykinin, aerosolized through the bronchoscope. Rp was measured after each challenge. At the end of the procedure, bronchoalveolar lavage was performed in both the challenged and a control segment. Fibrinogen content of recovered lavage fluids was measured as an index of plasma exudation. Bradykinin induced a dose-dependent increase in Rp in the asthmatics, but did not effect Rp in normal subjects. In asthmatics, there was no significant correlation between peripheral airways reactivity and whole lung reactivity to bradykinin. Fibronogen increased significantly in both groups after bradykinin challenge, and there was no significant difference between postchallenge levels for the two groups. Thus, hyperreactivity of the peripheral airways in asthmatics is not directly due to plasma exudation. The ability of bradykinin to increase peripheral airways resistance in asthmatic, but not in normal, subjects is consistent with a role of this peptide as a mediator of asthma.

Adult↗
PubMed1995

Three-dimensional structure of the bronchial microcirculation in sheep.

BACKGROUND: The bronchial circulation affects both pulmonary vascular and airway activity. Fundamental to understanding the role of the bronchial microcirculation in health and disease is understanding its anatomy. This study sought to identify specific structural elements that might contribute to the drop that occurs between the systemic blood pressure of the bronchial artery and the low pressure of the pulmonary bed into which the bronchial circulation flows and to better describe the connections of the bronchial and pulmonary circulations. METHODS: To do this, the lungs of five sheep were cast by injecting a resin through bronchial and pulmonary arteries. After taking samples for light microscopy, the tissue was digested and the casts were viewed with a scanning electron microscope. RESULTS: Casts of extrapulmonary bronchial arteries were structurally similar to other systemic arteries. Tortuous ones spiraled around bronchi and large blood vessels. Intrapulmonary bronchial arteries, about 100-300 microns in diameter, had sharp branching and deep focal constrictions with great rugosity that completely shut off the flow of the resin. These vessels correspond to the Sperrarterien described by von Hayek (and could cause the resistance associated with the pressure drop). Vasa vasorum ran in the walls of intrapulmonary pulmonary arteries for a variable distance before they entered the lumens of the pulmonary arteries. The smallest blood vessel found that was supplied with vasa vasorum was a bronchial artery 42 microns in diameter. Capillary-like networks with large luminal diameters were found on the pleural surface. CONCLUSIONS: Scanning electron microscopy of microvascular casts provides a fresh description of the bronchial circulation, further delineates the communications of these two circulations, and may structurally account for some pressure drop between the bronchial and pulmonary circulations.

Animals↗
PubMed1995

Polystyrene microspheres decrease bronchial artery resistance in anesthetized sheep.

The use of microspheres to measure tissue blood flow requires that the microspheres themselves do not alter regional arterial tone. To determine whether microspheres affected bronchial artery resistance, we cannulated and perfused the bronchial artery in anesthetized sheep. In seven sheep, the change in bronchial artery pressure at constant flow was recorded during infusion of 5 doses (1 x 10(5), 2 x 10(5), 5 x 10(5), 1 x 10(6), and 1.5 x 10(6)) of 15-microns microspheres. Microspheres produced a dose-dependent, self-limited decrease in bronchial artery pressure (1.5 x 10(6) microspheres decreased bronchial artery pressure by 36% for 31 min). This was a decrease in bronchial artery resistance, as evidenced by a shift in the slope, but not the intercept, of a pressure-flow curve (n = 4 sheep). Left atrial injection of 1 x 10(7) microspheres decreased bronchial artery resistance by 17% in six sheep with intact bronchial arteries in which flow was measured by ultrasound probe. The adenosine-receptor antagonist 8-phenyltheophylline attenuated the fall in resistance by 79% (n = 4 sheep). Cyclooxygenase inhibition by indomethacin attenuated the response by 37% (n = 4 sheep). These results suggest that microspheres caused the release of adenosine and a vasodilator prostaglandin. Repetitive measurements of bronchial blood flow by microspheres could overestimate true bronchial blood flow if the interval between measurements is < 30 min.

Animals↗
PubMed1995

Contribution of pulmonary versus systemic perfusion of airway smooth muscle.

Recent studies suggest a significant contribution of the pulmonary circulation to the perfusion of large airways. In this study we used anesthetized ventilated sheep (n = 19) to determine the functional contribution of the pulmonary circulation to airway smooth muscle. We performed sequential intravenous challenge with methacholine chloride (MCh; 0.25-2.5 mg/ml) to determine airway resistance (Raw) changes in the intact animal, after bronchial artery cannulation that essentially removed bronchial arterial delivery of MCh, and in an isolated lung preparation. After blocking the vagal reflex component of this response, we found that intravenous MCh in the intact preparation resulted in an average 2.2 +/- 0.5 cmH2O.l-1.s increase (181%) in Raw. After prevention of bronchial arterial delivery of MCh, Raw increased by 0.8 +/- 0.3 cmH2O.l-1.s (64%; P < 0.01 compared with intact preparation). In the isolated lung preparation, Raw increased by 0.6 +/- 0.2 cmH2O.l-1.s (63%; P < 0.01 compared with intact preparation). These results demonstrate that in sheep, the bronchial artery provides the major route for delivery of intravenously administered agonists to airway smooth muscle. Considering the large dilutional effect of an intravenously administered agonist by the time it reaches the bronchial artery, we conclude that the pulmonary component of agonist delivery to large airways is < 10% and unlikely to play a major physiological role.

Airway Resistance↗
PubMed1995

Peripheral airways responsiveness to cool, dry air in normal and asthmatic individuals.

Peripheral airways resistance (Rp) has been shown to be increased in asymptomatic asthmatic patients with normal spirometric values, and to be correlated with airways hyperresponsiveness to methacholine. We investigated whether Rp in asthmatic subjects with exercise-induced bronchospasm (EIB) would rise in response to cool, dry air. Using a wedged bronchoscope technique, we challenged an isolated lung segment with high flows (500 to 1,000 ml/min) of cool (22 degrees C) dry 5% CO2 in air for 5 min in eight asthmatic subjects with EIB and eight normal subjects. Baseline Rp and Rp following challenge were measured with saturated air at 37 degrees C at a flow rate of 100 ml/min. Baseline Rp was significantly greater in the asthmatic (0.09; [0.05 to 0.23] cm H2O/ml/min; median [interquartile range]) than in the normal subjects (0.05; [0.03 to 0.07] cm H2O/ml/min) (p = 0.04). The asthmatic, but not the normal subjects, had a significant absolute maximal increase in Rp following cool, dry air (0.10 [0.03 to 0.15] cm H2O/ml/min) (p < 0.01). In the asthmatic subjects, baseline Rp correlated with airways hyperresponsiveness to exercise (r = -0.76, p = 0.03). We conclude that the peripheral airways of asthmatic individuals with EIB are responsive to cool, dry air, and may play an important role in EIB.

Airway Resistance↗
PubMed1994

Role of the bronchial circulation in ischemia-reperfusion lung injury.

Bronchial arterial (BA) perfusion could modify pulmonary arterial (PA) ischemia-reperfusion (IR) injury by promoting clearance of peribronchial edema or limiting edema formation through maintenance of pulmonary vessel integrity via bronchopulmonary anastomotic or pulmonary vasa vasorum flow. The purpose of this study was to determine the effect of BA perfusion on IR injury in isolated sheep lungs. In 12 lungs (BA++) the BA was perfused throughout 30 min of PA ischemia and 180 min of reperfusion. In 12 lungs (BA-+) BA perfusion was begun with PA reperfusion, and in 15 lungs (BA--) the BA was never perfused. After 180 min, extravascular lung water was less (P < 0.05) in BA++ and B-+ lungs [4.70 +/- 0.16 and 4.57 +/- 0.18 g/g blood-free dry lung (bfdl)] than in BA-- lungs (5.23 +/- 0.19 g/g bfdl). The reflection coefficient for albumin was greater (P < 0.05) in BA++ and BA-+ (0.57 +/- 0.06 and 0.75 +/- 0.03) than in BA-- lungs (0.44 +/- 0.04). The filtration coefficient in BA++ and BA-+ lungs (0.016 +/- 0.006 and 0.015 +/- 0.006 g.min-1 x mmHg-1 x kg-1) was not different from that in BA-- lungs (0.025 +/- 0.006 g.min-1 x mmHg-1 x kg-1). These results suggest that BA perfusion decreased reperfusion edema by attenuating the increase in pulmonary vascular permeability caused by IR injury. Moreover the result in BA-+ lungs suggests that the protective effect was mediated by BA perfusion of PA vasa vasorum rather than bronchopulmonary anastomotic flow, which was trivial compared with PA blood flow.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Effects of increased bronchial blood flow on airway morphometry, resistance, and reactivity.

It has been suggested that airway obstruction may be mediated in part by airway vascular engorgement or airway wall edema. However, there are few data that support this conjecture. In this study we examined the effects of increased bronchial blood flow (Qba) on airway wall dimensions, conducting airway resistance, peripheral airway resistance, and airway reactivity assessed by methacholine aerosol challenge. The bronchial artery was perfused with autologous blood (control Qba = 0.6 ml.min-1.kg-1) in anesthetized ventilated sheep. The artery was perfused at either control (C) Qba or at high (H) Qba (300% of C Qba) for 3 h. Morphometry showed a doubling of the vascular area in airways exposed to H Qba (n = 4) compared with C Qba (n = 4). However, the significant increase in wall area could be accounted for only partially by the vascular changes, with edema fluid accumulation accounting for the major increase. Despite these changes, baseline airway resistance (n = 16) and peripheral airway resistance were both unaltered. Airway reactivity to methacholine before and after H Qba was also examined (n = 12). The 3 h of H Qba had no effect on airway reactivity regardless of whether challenge occurred with C or H Qba. The lack of effect of vascular engorgement on airway resistance or reactivity does not support a primary role for these factors in mediating airway obstruction.

Aerosols↗
PubMed1993

Edema clearance in isolated sheep lungs.

Edema may be cleared from the lung by lymphatic drainage, transudation across the visceral pleural, vascular reabsorption, and movement into the mediastinum. To determine the quantity and mechanisms of edema clearance associated with spontaneous edema formation in isolated sheep lungs, we perfused six lungs for 180 min with blood (100 ml.kg-1.min-1) at subatmospheric left atrial pressure (Pla) from a weighed reservoir. In six other lungs, Pla was increased to 20 mmHg at 30-75 min to further augment edema. Fluid drainage from the lung was fractionated into blood and water components by serial measurements of drainage and perfusate hematocrit. Changes in weight of circulating intravascular blood and extravascular lung water (EVLW) were also directly measured by dye dilution and standard gravimetric techniques, respectively. From these measurements, we calculated that 3.04 +/- 0.53 g/g blood-free dry lung of water filtered into the extravascular space during perfusion. Of this amount, 42% was reabsorbed into the pulmonary vasculature; 18% drained from the lung via lymphatics, visceral pleura, and mediastinum; and 40% was retained in the lung. Compared with low Pla lungs, transient elevation of Pla increased lung hemorrhage and the final change in reservoir weight, but the quantity and clearance of cumulative filtered water and the final values of EVLW and wet-to-dry weight ratio (WW/DW) were not altered. These results suggest that 1) significant edema clearance occurred in isolated sheep lungs, primarily by vascular reabsorption, and 2) measurements of EVLW and WW/DW under-estimated injury in the presence of lung hemorrhage and significant edema clearance.

Animals↗
PubMed1992

Peripheral airways resistance in smokers.

To determine peripheral airways resistance (Rp) in asymptomatic smokers, we used a wedged bronchoscope technique to study 19 volunteers (18 to 44 yr of age) who actively smoked for 2 to 28 pack-years. A fiberoptic bronchoscope was wedged in a subsegmental bronchus of the right upper lobe. Using a double lumen catheter inserted through the working channel of the bronchoscope, we infused 5% CO2 in air through one lumen and measured pressure through the second lumen. Rp was determined as the average of the peripheral resistance measured at three or more flow rates. This resistance ranged from 0.003 to 0.075 cm H2O/ml/min in the 19 subjects. We have previously shown normal subjects to have an average Rp of 0.009 +/- 0.002 cm H2O/ml/min (mean +/- SE) and asthmatic subjects an average of 0.069 +/- 0.017 cm H2O/ml/min. Thus, despite normal pulmonary function as assessed by spirometry, these asymptomatic smokers demonstrated a wide range of Rp values from normal to that observed in asthmatic subjects. These findings are consistent with a mechanism that considers the high resistance to result from inflammatory changes in the small airways.

Adolescent↗