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Biomedical subjects

R H Ingram

Publications and source records attributed to R H Ingram.

At least 91 records · Page 5Linked to original sources
PubMed1981

Inhalation patterns and predominant site of bronchoconstriction in healthy subjects.

To determine the relationship between changes in density dependence of maximal expiratory flow and changes in the predominant site of bronchoconstriction, we altered the pattern of inhalation of a methacholine aerosol to achieve deposition either centrally (by short choppy breaths) or peripherally (by slow deep breaths). Partial expiratory flow volume curves on air and on 80% helium-20% oxygen (HeO2) were recorded in six healthy subjects before and after each pattern of methacholine inhalation. We varied concentrations of methacholine and number of inhalations to achieve equivalent degrees of bronchoconstriction as assessed by decreases in maximal flow (Vmax) on air, which fell 27% from control values. Vmax on HeO2 also fell after both inhalation patterns. Density dependence (Vmax on HeO2 divided by Vmax on air) decreased following slow deep breaths of bronchoconstrictor aerosol, and increased following short choppy breaths. In three subjects, inhalation of radiolabeled methacholine aerosol confirmed that the slow deep pattern was associated with a diffuse, more peripheral deposition, whereas the short choppy pattern led to central deposition. We conclude that changes in density dependence reflect the predominant site of obstruction after acute methacholine aerosol challenge in healthy subjects.

Adult↗
PubMed1981

Direct and reflex bronchoconstriction induced by histamine aerosol inhalation in dogs.

Histamine aerosols were administered to nine anesthetized, paralyzed, mechanically ventilated mongrel dogs with the cervical vagi first intact, then sectioned, and then peripherally stimulated at two intensities. Pulmonary resistance (RL) was measured, and dose-response curves were constructed in the four conditions. All dogs had dose-related increases in RL with increasing histamine aerosol concentrations. After the vagi were cut, the degree to which constant levels of vagal stimulation altered the dose-response relationships was assessed by examining the slopes and positions of the RL vs. histamine curves. Four of the nine animals studied showed evidence of increasing vagal efferent activity as the concentration of histamine in the aerosol increased, but three did not. Two of the dogs had equivocal responses in that increasing activity was suggested but not clearly demonstrated. These results indicate that, in addition to direct effects of histamine, the extent of and basis for vagal interaction with this stimulus varies among dogs. The results suggest that the basis of vagal interaction is related to either constant efferent activity (tone) or increasing efferent activity (reflexes).

Aerosols↗
PubMed1981

Alveolar pressure-airflow characteristics in humans breathing air, He-O2, and SF6-O2.

In a system of rigid tubes under steady flow conditions, the coefficient of friction [CF = 2 delta P/(rho V2/A2)] (where delta P is pressure drop, rho is density, V is flow, and A is cross-sectional area) should be a unique function of Reynolds' number (Re). Recently it has been shown that at any given Re, the value of CF using transpulmonary pressure (PL) was lower when breathing He-O2 compared with air (Lisboa et al., J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 48: 878-885, 1980). One explanation for this discontinuity is that PL includes the pressure drop due to tissue viscance, which is independent of V, and thus would lead to an overestimate of CF on air compared with He-O2 at any Re. We tested this hypothesis by measuring V related to alveolar pressure, rather than PL, in normal subjects breathing air, He-O2, and SF6-O2. In each subject, for a given Re, CF was greatest breathing SF6-O2 and lowest breathing He-O2, similar to results using PL. Thus tissue viscance is not the sole cause of the discontinuous plot of CF vs. Re, and this phenomenon must be due to other factors, such as changing geometry or nonsteady behavior.

Adult↗
PubMed1981

Effects of lung inflation on airway and tissue responses to aerosol histamine.

The pulmonary effects of aerosol histamine exposure include an increase in pulmonary resistance (RL) and a decrease in dynamic compliance (Cdyn). These changes are substantially reversed by inflation of the lungs to 30 cmH2O transpulmonary pressure (TLC). Although histamine has been shown to change both the airway and tissue components of RL and Cdyn, it is not known whether lung inflation reverses the changes in airways, in tissue, or in both. We studied six anesthetized, paralyzed, open-chest dogs. We sequentially measured RL and Cdyn during oscillations in lung volume at 0.6 Hz with the airway open and during compression-decompression of the lungs without tracheal airflow. In the control state after saline aerosol, inflation to TLC resulted in a slight increase in compliance and a decrease in the tissue component of RL. Aerosol histamine exposure caused an increase in resistance and a decrease in compliance due to both airway and tissue changes. Inflation of the lungs to TLC largely reversed the changes due to airway constriction without consistently affecting the changes due to tissue. We conclude that after histamine exposure smooth muscle responsible for airway narrowing is stretched by lung inflation but that contractile elements responsible for alterations in air-space distensibility and hysteresis of dynamic lung recoil are either not stretched by lung inflation or are stretched and shorten again rapidly.

Aerosols↗
PubMed1981

Effects of cromolyn sodium on the response to respiratory heat loss in normal subjects.

To investigate whether premedication with cromolyn sodium blunts the bronchoconstrictor response that occurs in normal subjects after extreme degrees of airway cooling, we had 9 adult male inhale either cromolyn or placebo on separate days, in a random, double-blind fashion, before challenges with cold air. The latter consisted of eucapnic hyperventilation to levels in excess of 85% of the indirect maximal breathing capacity while the subjects breathed air at -13 degrees C. Partial and maximal expiratory flow-volume curves were measured before and after medication and after hyperventilation. Neither cromolyn nor placebo inhalation per se significantly affected pulmonary function. The cold-air challenges caused significant decreases in expiratory flows, and these changes were significantly attenuated by cromolyn but not placebo. Thus, in normal subjects, cromolyn has the ability to modify the airway response to respiratory tract heat loss. Because the subjects were free of sensitized airway mast cells, we interpret these findings as further evidence that cromolyn sodium has immunologic and nonimmunologic modes of action.

Adult↗
PubMed1981

CO2 elimination by high frequency ventilation (4 to 10 Hz) in normal subjects.

We measured the rate of CO2 elimination (VCO2) by oscillatory high frequency ventilation (HFV) in 8 normal subjects and studied the effects of varying frequency, stroke volume, lung volume, and bronchodilation on VCO2. Subjects breath-held while a loudspeaker at the mouth sinusoidally forced low volumes (15 to 150 ml) of air at a high frequency (4 to 10 Hz) into the respiratory system. The CO2 eliminated from the lungs was washed out by a bias flow at the mouth. In each of 6 subjects studied, VCO2 was greater at 8 Hz than at 4 Hz (130 versus 74 ml/min; p less than 0.05) with oscillation volumes (VT) of 100 ml. At a fixed frequency of 10 Hz there was a positive linear correlation (p less than 0.01) between oscillation volume and VCO2. At a lung volume 500 ml below total lung capacity VCO2 ranged from 130 to 215 ml/min at a mean VT of 130 ml and 5 to 60 ml/min at a VT of only 10% of the estimated anatomic dead space. In 3 subjects, after inhalation of isoproterenol, there was a greater VCO2 over the entire vital capacity (p less than 0.01). We concluded that HFV can achieve values of CO2 elimination close to the estimated metabolic CO2 production in normal unintubated subjects over short periods of time.

Carbon Dioxide↗
PubMed1981

Airway responsiveness to inhaled mediators: relationship to epithelial thickness and secretory cell number.

Naturally occurring variations in airway responsiveness to inhaled mediators were correlated with various anatomic indexes thought to be related to airway responsiveness. Specifically, the airways of 2 relatively unresponsive and 3 relatively responsive dogs were compared in terms of epithelial thickness, secretory cell number, smooth muscle thickness, and airway mucous gland number and size. More responsive dogs were found to have thinner epithelium and higher secretory cell counts than less responsive dogs. No significant differences between the 2 groups were noted with respect to smooth muscle thickness or mucous gland number and size. Although these observations identify an association between these anatomic features and airway responsiveness, it does not imply a causal relationship.

Airway Resistance↗
PubMed1981

Effects of frequency, tidal volume, and lung volume on CO2 elimination in dogs by high frequency (2-30 Hz), low tidal volume ventilation.

Recent studies have shown that effective pulmonary ventilation is possible with tidal volumes (VT) less than the anatomic dead-space if the oscillatory frequency (f) is sufficiently large. We systematically studied the effect on pulmonary CO2 elimination (VCO2) of varying f (2-30 Hz) and VT (1-7 ml/kg) as well as lung volume (VL) in 13 anesthetized, paralyzed dogs in order to examine the contribution of those variables that are thought to be important in determining gas exchange by high frequency ventilation. All experiments were performed when the alveolar PCO2 was 40 +/- 1.5 mm Hg. In all studies, VCO2 increased monotonically with f at constant VT. We quantitated the effects of f and VT on VCO2 by using the dimensionless equation VCO2/VOSC = a(VT/VTo)b(f/fo)c where: VOSC = f X VT, VTo = mean VT, fo = mean f and a, b, c, are constants obtained by multiple regression. The mean values of a, b, and c for all dogs were 2.12 X 10(-3), 0.49, and 0.08, respectively. The most important variable in determining VCO2 was VOSC; however, there was considerable variability among dogs in the independent effect of VT and f on VCO2, with a doubling of VT at a constant VOSC causing changes in VCO2 ranging from -13 to +110% (mean = +35%). Increasing VL from functional residual capacity (FRC) to the lung volume at an airway opening minus body surface pressure of 25 cm H2O had no significant effect on VCO2.

Animals↗
PubMed1980

Effective pulmonary ventilation with small-volume oscillations at high frequency.

At high oscillation frequencies (4 to 30 hertz), effective alveolar ventilation can be achieved with tidal volumes much smaller than the anatomic dead space. An explanation of this phenomenon is given in terms of the combined effects of diffusion and convection and in terms of data consistent with the hypothesis. Theory and experimental results both show that the significant variable determining the effectiveness of gas exchange is the amplitude of the oscillatory flow rate independent of the individual values of frequency and stroke volume.

Animals↗
PubMed1980

Magnitude and site of airway response to exercise in asthmatics in relation to arterial histamine levels.

In order to determine if there is a relationship among arterial histamine levels, state of disease activity, and the magnitude and site of obstruction in exercise-induced asthma, we recorded airway resistance, lung volumes, spirometry, and density dependence of maximum expiratory flow before and after an exercise challenge in 17 asymptomatic individuals. These observations were then related to the concentration of histamine in systemic arterial blood. This study demonstrates that those individuals whose disease process was the most active at the time of investigation had more depressed lung function and higher baseline histamine levels, and responded to the challenge with severe obstruction that involved the airways in the periphery of the lung. In contrast, those subjects whose underlying disease was more quiescent had lower histamine values and the response to provocation was less severe and predominated in the larger airways. In neither group did the postchallenge values for histamine increase. It is suggested that the factor that determines these patterns of response is the state of inflammation of the airways, for which histamine may serve as a marker.

Adult↗
PubMed1980

In vivo effect of cimetidine on canine pulmonary responsiveness to aerosol histamine.

A series of experiments were designed to discover whether pulmonary histamine H2 receptors might be of physiologic importance in vivo in the dog. Dose-response curves were performed to aerosol histamine in 11 dogs both before and 1 hr after H2 receptor blockade with cimetidine (1 mg/kg as a rapid intravenous infusion). Cimetidine had no significant effect on control values of dynamic compliance or resistance of the lung. In the 11 dogs tested H2 receptor antagonism significantly potentiated (p less than 0.05) the animals' pulmonary responsiveness to aerosol histamine. The potentiation of histamine constrictor e-fects produced by cimetidine were more marked on those dogs initially least responsive to aerosol histamine (p less than 0.01). We have found evidence for the presence of inhibitory H2 receptors in canine airways and for the distribution of these receptors among dogs, explaining in part the previously described differences among dogs in the pulmonary responsiveness to aerosol histamine.

Aerosols↗
PubMed1980

Effects of atropine on respiratory heat loss in asthma.

We have previously observed that although atropine does not alter the magnitude of the response to exercise while breathing cold air, it does cause the predominant site of obstruction to move into the lung periphery. To determine if this effect was due to changes in the conditioning of inspired air, we measured respiratory heat loss (RHL) and retrotracheal (Trt) and retrocardiac esophageal temperature in eight asthmatics while they performed eucapnic hyperventilation with cold air before and after the inhalation of atropine. Multiple aspects of pulmonary mechanics were also recorded. Significant and equivalent airway obstruction developed with and without atropine (control delta FEV1 = 1.0 +/- 0.2 (SE) liter; postatropine = 0.9 +/- 0.3 liter). Despite this, RHL was 17.1% greater and Trt fell 16% more after atropine. These data demonstrate that atropine can influence heat transfer within the lung and alter the sites of conditioning.

Adult↗
PubMed1980

Nonhomogeneous alveolar pressure swings in the presence of airway closure.

When thoracic gas volume (TGV) is determined plethysmographically, it is assumed that the alveolar pressure swings are homogeneous and are appropriately represented by pressure swings at the mouth. However, recent studies have demonstrated differences in total lung capacities derived from TGV measurements made at different levels in the vital capacity. These differences suggested that, in the presence of airway closure, alveolar pressure swings may be nonhomogeneous during a TGV determination. This possibility was tested in six dogs. Pressure at the airway opening (ao) was measured from an endotracheal catheter. A balloon-tipped catheter was passed into the right lower lobe (RLL) bronchus for measurement of RLL pressure. delta PRLL -- delta Pao was monitored during inspiratory efforts with the airway opening occluded. With the RLL balloon inflated, delta PRLL always exceeded delta Pao by an amount averaging 8.2%. Induction of a pneumothorax eliminated all differences between delta PRLL and delta Pao. Thus, during a TGV measurement, the chest wall may apply to the lungs nonhomogeneous forces that, in the presence of airway closure (e.g., chronic obstructive pulmonary disease and asthma) would result in nonhomogeneous alveolar pressure swings and potentially significant errors in the plethysmographic determination of TGV.

Animals↗
PubMed1980

Activation of upper airway muscles before onset of inspiration in normal humans.

Animal studies have shown activation of upper airway muscles prior to inspiratory efforts of the diaphragm. To investigate this sequence of activation in humans, we measured the electromyogram (EMG) of the alae nasi (AN) and compared the time of onset of EMG to the onset of inspiratory airflow, during wakefulness, stage II or III sleep (3 subj), and CO2-induced hyperpnea (6 subj). During wakefulness, the interval between AN EMG and airflow was 92 +/- 34 ms (mean +/- SE). At a CO2 level of greater than or equal to 43 Torr, the AN EMG to airflow was 316 +/- 38 ms (P < 0.001). During CO2-induced hyperpnea, the AN EMG to airflow interval and AN EMG magnitude increased in direct proportion to CO2 levels and minute ventilation. During stages II and III of sleep, the interval between AN EMG and airflow increased when compared to wakefulness (P < 0.005). We conclude that a sequence of inspiratory muscle activation is present in humans and is more apparent during sleep and during CO2-induced hyperpnea than during wakefulness.

Adult↗
PubMed1980

Airway effects of respiratory heat loss in normal subjects.

The increased minute ventilation (VE) associated with exercise produces similar degrees of airway cooling in normal and asthmatic subjects, but only those with asthma develop postexertional bronchoconstriction in response to this stimulus. We have found that when normal subjects breathing subfreezing air perform isocapnic hyperventilation to levels exceeding those associated with even exhausting exercise, 1-s forced expiratory volumes and maximum midexpiratory flow rates fall significantly. When tests more sensitive in detecting bronchoconstriction are employed, changes are seen at lower levels of hyperventilation that simulate the VE associated with moderately heavy work loads. We conclude that normal subjects respond to airway cooling, but are much less sensitive than those with asthma.

Adult↗
PubMed1980

Airway responsiveness to cold air and hyperpnea in normal subjects and in those with hay fever and asthma.

Multiple aspects of pulmonary mechanics were measured before and after bronchial challenges consisting of hyperpnea with cold air inhalation in 20 normal control subjects, 16 subjects with hay fever, and 44 asymptomatic asthmatics. These challenges had no effect on the lung function of the normal subjects. In the hay fever group, however, postchallenge mechanics changed a small, but significant, amount, e.g., mean decrease in forced expiratory volume in one second (FEV1) was -5.1 +/- 1.7% (SEM). The asthmatics had a much more marked response (mean fall in FEV1, -32.7 +/- 2.6%). There was considerable overlap between the responses of the normal subjects and those with hay fever, but no overlap at all between asthmatic and normal subjects. The only subjects with hay fever whose responses overlapped the asthmatic response were those who had histories of occasional episodes of wheezing. This pattern of response suggests that the use of hyperpnea and subfreezing air is a very sensitive and highly specific means of detecting increased air reactivity.

Adult↗
PubMed1980

The effects of cromolyn sodium on the airway response to hyperpnea and cold air in asthma.

In order to determine if cromolyn sodium provided protection against the marked bronchoconstriction that develops when the hyperpnea of exercise is combined with frigid air, we exposed a group of asymptomatic asthmatics to this stimulus, with and without pretreatment with this drug. Respiratory heat loss and retrotracheal and retrocardiac esophageal temperatures were measured during each challenge, and multiple aspects of pulmonary mechanics were recorded before commencement and after completion. The results demonstrated that, unlike anticholinergic agents, cromolyn sodium attenuates the obstructive response observed with these large thermal burdens, and does so without affecting airway cooling.

Adult↗