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Biomedical subjects

R H Ingram

Publications and source records attributed to R H Ingram.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effect of tidal volume and anesthetic agent on airway responsiveness to histamine.

Dose-response relationships for bronchoconstriction in response to aerosal histamine were assessed before and after vagotomy in 11 dogs anesthetized with barbiturates and in 9 dogs anesthetized with alpha-chloralose-urethan. The dose-response relationships following vagotomy were assessed during spontaneous ventilation and during muscular paralysis and mechanical ventilation with tidal volume (VT) similar to each animal's VT prior to vagotomy. After vagotomy the spontaneous VT of both groups increased but the VT of the alpha-chloralose-urethan group was significantly less than that of the barbiturate group. The histamine responsiveness of the animals anesthetized with barbiturates was significantly greater during mechanical ventilation when VT was reduced to prevagotomy levels compared with during spontaneous ventilation. In contrast, the histamine responsiveness of the alpha-chloralose-urethan group was not significantly changed by reducing VT to prevagotomy levels. In six other dogs anesthetized with pentobarbital sodium and studied after vagotomy, responsiveness to histamine aerosol during controlled ventilation with breaths of prevagotomy VT was greater than responsiveness during mechanical ventilation with large volume breaths given immediately afterward. Thus the magnitude of VT of dogs after vagotomy may influence airway responsiveness, and the influence of anesthetic agents on airway responsiveness after vagotomy may in part be due to their effects on VT. Furthermore, bronchodilation accompanying large volume ventilation persists after vagotomy, suggesting that it is not exclusively mediated by changes in parasympathetic activity.

Airway Resistance↗
PubMed1986

CO2 elimination by high-frequency oscillation: effects of vagosympathetic stimulation.

The effects of electrical stimulation of the vagi on gas transport mediated by high-frequency, low tidal volume ventilation (HFV) was examined in 10 anesthetized, paralyzed, propranolol-treated dogs. Gas transport efficiency was estimated by measuring the rate of CO2 removed from the lungs (Vco2) achieved during 45-s bursts of HFV applied before (control 1), during, and after (control 2) electrical stimulation of the transected vagi. During vagal stimulation the heart rate was maintained by electrical pacing. During the 15-s phase of vagal stimulation pulmonary impedance increased from 3.6 +/- 0.7 to 6.2 +/- 2.2 cmH2O X l-1 X s, and Vco2 increased. When the electrical stimulation of the vagi was stopped, impedance and Vco2 returned to prestimulation values. Vco2 was always higher during electrical stimulation of the vagi when HFV of a fixed volume was applied over a range of frequencies or when a fixed oscillation frequency was used over a range of tidal volumes. The effects of vagal stimulation on HFV-mediated gas transport were quite similar to the effects of moving the locations of the bias flow inlet and outlet into the lung such that tracheal volume was decreased by 20 ml, an amount equivalent to estimated change in control airway volume thought to occur during vagal stimulation. We simulated the effects of vagal stimulation and decreased tracheal volume on Vco2 by using a previously described model of HFV-mediated gas transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Circulatory heat sources for canine respiratory heat exchange.

We assessed the roles of the pulmonary and bronchial circulations as potential heat sources to the pulmonary airways during respiratory heat loss, by observing the changes in airstream temperature that accompanied temporary occlusion of the pulmonary or bronchial circulations. Baseline end-expiratory and end-inspiratory airstream temperatures were 35.4 +/- 0.2 degrees C (SEM) and 30.9 +/- 0.3 degrees C, respectively, among all trials. With occlusion of the lower lobe pulmonary arteries for 3 min ipsilateral end-expiratory and end-inspiratory airstream temperatures fell by 2.8 +/- 0.2 and 1.1 +/- 0.2 degrees C, respectively, during hyperpnea with room temperature air, and by 3.5 +/- 0.5 and 1.8 +/- 0.2 degrees C, respectively, during hyperpnea with frigid air. In marked contrast, interruption of the bronchial circulation for 3 min had no effect on airstream temperatures. These data indicate that under these conditions, the pulmonary circulation, but not the bronchial circulation, serves as an important local heat source for respiratory heat exchange within the pulmonary airways.

Animals↗
PubMed1985

Radiographic visualization of airway wall movement during oscillatory flow in dogs.

It has been suggested that radial movement of the central airway walls during oscillatory flow might contribute to the increased frequency dependence of compliance seen in chronic obstructive pulmonary disease (COPD) (J. Appl. Physiol. 26: 670-677, 1969). Radial airway wall motion has also been invoked to explain the frequency-dependent decreases in the efficiency of gas exchange during low-volume high-frequency ventilation (HFV) in histamine-bronchoconstricted dogs and in patients with respiratory insufficiency. To test the possibility that airway wall motion increases with bronchoconstriction, we measured central airway diameters using cinebronchoradiography in anesthetized tracheostomized dogs during oscillatory HFV [50 and 100 ml tidal volume (VT) at frequencies (f) of 2, 6, and 12 Hz], under control conditions, during electrical stimulation of the vagi, and after exposure to histamine aerosol. Cineradiobronchograms from two dogs were evaluated quantitatively for tracheal diameter and for lengths and diameters of a number of major airways. Under control conditions, the diameter of the airways fluctuated 7-9% of the mean with VT of 50 ml and 9-18% with VT of 100 ml in the range of frequencies studied. Bronchoconstriction produced by aerosolized histamine increased radial airway wall movement to 10-47% with VT of 50 ml, and during vagal stimulation diameters changed 7-20% at VT of 50 ml. After histamine, the central airways displayed large diameter changes during HFV, whereas more peripheral airways were markedly constricted and did not change in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Configuration of maximum expiratory flow-volume curve: model experiments with physiological implications.

A two-compartment mechanical model of the lungs was constructed with two parallel peripheral and collapsible bronchi in series with one central and collapsible trachea. Maximal expiratory flow-volume (MEFV) curves similar to those obtained in most dogs and in some humans could be produced: a peak followed by a gently sloping plateau ending in a knee, where flow suddenly fell to a much smaller value approaching zero rather slowly over the last 25 to 50% of the expired vital capacity. It was shown that flow before the knee was limited in the trachea, and after the knee it was limited in the bronchi. Two patterns of changes in the configuration of the MEFV curve could be observed. Pattern of changes affecting the central airway, at a given volume, maximal flow during the first part of the expiration (i.e., before the knee) is decreased; the knee occurs at a lower lung volume; the flow at the beginning of the knee is decreased. This pattern was observed with the following interventions: decreased cross-sectional area of the trachea (partial obstruction); decreased axial tension of the trachea; and, increased frictional loss between the trachea and the bronchi. Pattern of changes affecting the airways in the periphery: the knee occurs at a higher lung volume; at a given volume, flow after the knee becomes smaller; the absolute flow at the start of the knee is almost unchanged. This pattern was observed with the following interventions: decreased cross-sectional area of the peripheral airways (partial obstruction); increased frictional loss upstream to the peripheral airways; and, decreased elastic recoil pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Chest wall distortion during resistive inspiratory loading.

We studied six (1 naive and 5 experienced) subjects breathing with added inspiratory resistive loads while we recorded chest wall motion (anteroposterior rib cage, anteroposterior abdomen, and lateral rib cage) and tidal volumes. In the five experienced subjects, transdiaphragmatic and pleural pressures, and electromyographs of the sternocleidomastoid and abdominal muscles were also measured. Subjects inspired against the resistor spontaneously and then with specific instructions to reach a target pleural or transdiaphragmatic pressure or to maximize selected electromyographic activities. Depending on the instructions, a wide variety of patterns of inspiratory motion resulted. Although the forces leading to a more elliptical or circular configuration of the chest wall can be identified, it is difficult to analyze or predict the configurational results based on insertional and pressure-related contributions of a few individual respiratory muscles. Although overall chest wall respiratory motion cannot be readily inferred from the electromyographic and pressure data we recorded, it is clear that responses to loading can vary substantially within and between individuals. Undoubtedly, the underlying mechanism for the distortional changes with loading are complex and perhaps many are behavioral rather than automatic and/or compensatory.

Abdominal Muscles↗
PubMed1985

Nonhomogeneity of lung response to inhaled histamine assessed with alveolar capsules.

To assess the homogeneity of airway responses to inhaled histamine we examined regional alveolar pressure excursions (PA) arising from small-amplitude oscillations applied at the airway opening (Pao). In five anesthetized and vagotomized dogs the sternum was split and the anterior right lung field exposed. PA was sampled using four capsules affixed to the right apical and middle lobes while lung impedance (ZL) and airway impedances (Zaw) were measured during conventional tidal breathing and during forced oscillations (2-60 HZ at 10 cmH2O distending pressure). During tidal breathing after exposure to aerosol histamine regional PA's could be separated into three groups by plotting Lissajous figures of PA vs. Pao: PA in phase with Pao (no looping), PA lagging Pao (moderate looping), and PA decreasing while Pao was increasing and vice versa (paradoxical looping), suggesting unresponsive, responsive, and closed pathways, respectively, between the airway opening and specific alveolar zones. During high-frequency oscillation the corresponding PA spectra were markedly different from control spectra and revealed resonant amplification, overdamped resonance, and marked attenuation, respectively. With induced bronchospasm resonant amplification of PA was damped on average. However, the more obstructed and closed pathways were protected from resonant amplification, and the more open (nonlooping) pathways were subjected to resonant amplification greater than in the control state. In spite of this markedly nonhomogeneous behavior, frequency dependence of ZL was consistent with the model by Mead (J. Appl. Physiol. 26: 670-673, 1969), which ignores nonhomogeneity of peripheral compartments. These data demonstrate that the response of airways to inhaled histamine is nonhomogeneous but that frequency dependence of ZL above 2 Hz is not sufficient to characterize this nonhomogeneity.

Aerosols↗
PubMed1985

Effects of deep inhalation in asthma: relative airway and parenchymal hysteresis.

Asthmatic subjects were screened for the effects or volume history on the degree of induced airway obstruction with methacholine by comparing isovolumic maximal expiratory flows (Vmax) from partial expiratory flow-volume curves (P) begun near functional residual capacity (FRC) followed by maximal expiratory flow-volume (M) maneuvers begun from total lung capacity (TLC). The isovolumic Vmax values from M and P maneuvers defined two groups: one had a high M/P ratio (high group), indicating a large degree of reversal with deep inhalation, another had a low M/P ratio (low group), indicating minimal reversal. No differences were found between groups. A more complete study was later performed in which we measured specific airway conductance (sGaw) and anatomical dead space (VD) as indices of airway size and hysteresis before and after deep inhalation. The area of quasi-static transpulmonary pressure (Ptp) volume (V) curves from FRC to TLC and back to FRC was measured as an index of parenchymal hysteresis. At base line both groups showed a decrease in both sGaw and VD after a deep inhalation (DI). After constriction neither group changed VD after DI, whereas sGaw increased significantly in the high group after DI. This suggests that dilation of airways with DI occurred peripheral to those contributing to VD in the high group. The areas of the Ptp-V curves were equal at base line; yet the increase in areas with constriction in the low group was much greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Airway dynamics in transition between peak and maximal expiratory flow.

Expiratory flow-volume curves with periodic interruption of flow showed flow transients exceeding maximal flow (Vmax) measured on the maximum expiratory flow-volume (MEFV) curve in a mechanical lung model and in five tracheotomized, vagotomized, open-chest, anesthetized dogs. Direct measurement of flow from the collapsing model airway showed that the volume of the flow transients in excess of the MEFV envelope was greater than that from the collapsing airway. Determination of wave-speed flows from local airway transmural pressure-area curves (J. Appl. Physiol. 52: 357-369, 1982) and photography of the airway led to the following conclusions. Flow transients exceeding Vmax are wave-speed flows determined by an initial and unstable configuration of the flow-limiting segment (FLS) with maximum compression in the midportion. The drop in flow from the peak to the following plateau is due to development of a more stable airway configuration with maximum compression at the mouthward end with a smaller area and a smaller maximal flow. When FLS jumps to a more peripheral position, the more distal airways may pass through similar configurational changes that are responsible for the sudden decrease of flow (the "knee") seen on most MEFV curves from dogs.

Animals↗
PubMed1985

Breathing pattern affects airway wall temperature during cold air hyperpnea in humans.

We studied the influence of flow rate on respiratory heat exchange in 9 healthy adult subjects using a new noninvasive technique, the single-breath temperature washout (SBTW) curve. The SBTW curve is a plot of exhaled gas temperature versus exhaled volume during a standard exhalation and consists of an initial rise (within the first 200 ml) to a plateau temperature that persists through the remainder of exhalation. We found that exhaled gas temperatures within the initial expirate were colder at every airway locus than corresponding intra-airway gas temperatures at end-inspiration, suggesting that heat exchange occurs between lumenal gas and the relatively cooler airway walls during exhalation. The SBTW plateau temperatures were: (1) lower after preconditioning the airways with rapid (80 L/min) isocapnic hyperpnea of frigid air than after less rapid (40 L/min) cold-air hyperpnea or after quiet breathing; (2) lower when, after identical airway preconditioning regimens, the SBTW exhalation was performed with a slower (0.5 versus 2.5 L/s) expiratory flow; and (3) lower when SBTW curves were obtained after airway preconditioning using respiratory patterns with larger inspiration-expiration duration (I:E) ratios (5:1 versus 1:5) at fixed minute ventilation and respiratory rate. Our results indicate that the global respiratory gas-wall heat transfer coefficient increases with velocity to the 0.9 power, a finding similar to that in previous studies of turbulent flow in rigid pipes.

Adult↗
PubMed1984

Intra-airway gas mixing during high-frequency ventilation.

We examined the intra-airway gas transport mediated by high-frequency oscillations (HFO) in 10 nonintubated healthy volunteers using a method based on comparisons of single-breath N2-washout curves obtained after various durations of breath hold or high-frequency oscillations. With a mathematical analysis based on Fick's law of diffusion we computed the local transport parameter, effective diffusivity, during oscillations of frequency 2-24 Hz and tidal volume 10-120 ml and during breath hold alone. Local effective diffusivity increased with both oscillatory frequency and tidal volume at all levels in the tracheobronchial tree; the enhancing effect of tidal volume on local effective diffusivity was more pronounced than that of frequency so that effective diffusivity was greater with larger tidal volume at fixed frequency-tidal volume product (f . VT). The greatest enhancement of gas mixing within the lung during HFO (over breath hold) was seen in the central airways. In previous studies examining CO2 removal rate during HFO (J. Clin. Invest. 68: 1475, 1981), we found that CO2 output was also greater with larger tidal volume at fixed f . VT, and we attributed this to an end constraint imposed by a fresh gas bias flow. Results of the current study, performed without a bias flow, indicate that bias flow end constraint does not solely account for the observed dependence of CO2 output on frequency and tidal volume.

Adult↗
PubMed1984

Morphologic correlation of physiologic changes caused by SO2-induced bronchitis in dogs. The role of inflammation.

Chronic bronchitis was induced in 6 mongrel dogs by exposure to SO2 gas for 6 to 18 months. All of the dogs developed cough and mucus hypersecretion. Chronic airway obstruction and decreased airway responsiveness to inhaled histamine developed in 5 of the dogs. Histologic changes in dogs evaluated after SO2 exposure included significant mucous gland hypertrophy and hyperplasia, epithelial thickening, and a decrease in the number of luminal cells containing undischarged secretory granules. Acute and chronic inflammation were found in the dogs with airway obstruction and decreased responsiveness to histamine, but such inflammation was absent in the one dog that failed to develop physiologic changes. After a period of recovery from SO2 exposure of 9 to 21 months, inflammation regressed dramatically and the other histologic changes returned toward normal. Physiologic changes regressed somewhat in those dogs that had had changes. These findings suggest that inflammation may be an important factor influencing the development of airway obstruction and altered airway responsiveness in the setting of chronic bronchitis.

Airway Resistance↗
PubMed1984

Airways responsiveness in a population sample of adults and children.

Nonspecific bronchial responsiveness was assessed with eucapneic hyperpnea to subfreezing air in a population-based sample of 134 adults and 213 children in East Boston, Massachusetts. Increased responsiveness was considered to be present if the decrease in forced expiratory volume in one second with cold air divided by the initial vital capacity was greater than 9%. Men and women had similar bronchial responsiveness, but children and young adults (24 yr of age and younger) were significantly more likely to be responders than were older subjects (p less than 0.001). Children with a doctor's diagnosis of asthma at any time in the past were twice as likely (42.9%) to be responders as were nonasthmatic children (19%) (p = 0.004). Ninety-two percent (11/12) of currently active asthmatics were responders. However, a large percentage of asymptomatic children had increased levels of bronchial responsiveness (18.9%). This cross-sectional study demonstrates the feasibility of measurement of nonspecific bronchial responsiveness in epidemiologic studies, and its relationship to age and wheeze symptoms in children.

Adult↗
PubMed1984

The relationship of airways responsiveness to cold air, cigarette smoking, and atopy to respiratory symptoms and pulmonary function in adults.

The response to eucapnic hyperventilation with subfreezing air was studied in a population based sample of 171 adults, all of whom also completed a respiratory questionnaire, spirometry, and skin testing. A positive response to the cold air challenge was defined as [initial FEV1-post-challenge FEV1)/initial FVC) X 100) greater than or equal to 9%. Cigarette smoking was with a positive cold air response: 12 of 128 current and ex-smokers (9.4%) versus 1 of 43 nonsmokers (2.3%) (p = 0.095). Among current and ex-smokers, a positive response to the cold air challenge was significantly associated with asthma (p = 0.046). Using a logistic regression model, both current smoking and response to cold air were significant predictors of the presence of "persistent wheeze" or asthma. A positive skin test to any of the 4 environmental antigens used (ragweed, housedust, trees, and grasses) was significantly associated with cigarette smoking (p = 0.018) and hay fever (p = 0.003 among current and ex-smokers) but not with wheezing or asthma. Though not statistically significant, cold air responders had a lower percentage of positive skin test reactivity than nonreactors. The findings of this cross-sectional analysis suggest that in adults, both airways responsiveness and cigarette smoking are important predictors of wheezing and asthma. Furthermore, the data suggest that airway hyperresponsiveness and atopy are independent traits. However, in adults, these traits are associated with cigarette smoking, a common environmental exposure.

Child↗
PubMed1983

Relationship between bronchial responsiveness to hyperventilation with cold and methacholine in asthma.

Twenty-seven subjects with asthma and normal baseline lung function were challenged with aerosols of methacholine (M) and by isocapnic hyperventilation with cold air (HV). Stimulus-effect relationships were determined for each provocational technique on separate days and were expressed as the dose required to produce a 20% fall in forced expired volume in 1 sec (FEV1) obtained by linear interpolation from log stimulus vs. response curves (PD20). Each stimulus was applied with a sufficient intensity to produce a 20% or greater fall in FEV1 in each subject. The PD20 for M correlated significantly with the PD20 for HV (p less than 0.001) when the latter was expressed in liters per minute. The correlation between cumulative M PD20 and HV PD20 expressed as a percent of maximal voluntary ventilation was significant but less strong. We conclude that the airway response to HV reflects nonspecific bronchial hyperresponsiveness and that the dose of HV is best determined as the absolute level of ventilation.

Adolescent↗
PubMed1983

Exercise-induced airway obstruction.

Many previous discrepancies and conflicts concerning the pathophysiology of EIAO have been explained or reconciled by the observation that respiratory heat loss and concomitant airway cooling relate directly and probably causally to both the occurrence and magnitude of the airway obstruction that develops. Recent measurements have documented and quantitated observations made centuries ago. Controversy continues concerning the role of mediator release and the relative contribution of vago-vagal reflexes to the response induced by airway cooling. Recent attempts to study the effects of cooling on both the responsiveness and metabolic processes of airway smooth muscle may well ascend the phylogenetic scale to the intact organism, eventually allowing the testing of hypotheses raised along the way. Meanwhile, we think it likely that airway cooling and the response to it will represent another example of nonspecific airway responsiveness, and that the links between this stimulus and the subsequent response will be multifactorial. The relative roles and interactive potentials of diverse processes will make the next step in understanding difficult, though not impossible.

Asthma↗