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Biomedical subjects

R H Ingram

Publications and source records attributed to R H Ingram.

At least 109 records · Page 6Linked to original sources

A reassessment of the effects of oropharyngeal anesthesia in exercise-induced asthma.

To investigate the possibility that stimulation of neural receptors in the posterior pharynx plays a role in the pathogenesis of exercise-induced asthma, we had 10 asthmatic subjects simulate the hyperpnea of exercise by performing eucapnic hypervenilation in the presence and absence of oropharyngeal anesthesia induced by lidocaine. During these studies, the amount of ventilation and temperature and water content of the inspired air were rigorously controlled in order to keep respiratory heat loss constant for each trial. Multiple aspects of pulmonary mechanics were measured before and after the pharynx was sprayed with either water or lidocaine, as well as after the completion of the bronchial challenge. Neither agent, in and of itself, produced alterations in lung function at rest. Eucapnic hyperventilaltion was followed by a significant reduction in pulmonary mechanics in both situations, and there were no significant differences between the effects of lidocaine or water. Thus, we were unable to find any evidence for the existence of "irritant-like" receptors essential to the pathogenetic consequences of airway cooling in the posterior pharynx.

Adult↗

Comparison of the responsiveness to histamine and to Ascaris suum challenge in dogs.

The pulmonary and dermal sensitivity of a group of mongrel dogs to an extract of Ascaris suum protein was compared with the pulmonary and dermal sensitivity to histamine in this same group. We found a modest but significant correlation in the entire population between skin test reaction to histamine and to A. suum protein (r = 0.52, p < 0.05), but when the skin test results were compared with those of aerosol challenge, no significant correlation was found. However, when those dogs with reactions to histamine challenge that fell within a narrow range were considered as a separate group, there was a significant correlation between the reactions of aerosol challenge with A. suum and those of the skin tests with A. suum (r = 0.56, p < 0.025). These findings were consistent with the hypothesis that aerosol bronchoconstrictor responsiveness and immunologic responsiveness are separate attributes that combine to determine airway responsiveness to a specific antigen.

Animals↗

Evaluation of role played by mediators of immediate hypersensitivity in exercise-induced asthma.

To determine whether mediators of immediate hypersensitivity played a role in the pathogenesis of exercise-induced asthma, we measured the concentration of histamine and neutrophil-chemotactic activity present in systemic arterial blood during thermal challenges in five asymptomatic asthmatics. Because exercise-induced asthma has been shown to be a result of respiratory heat loss and because respiratory heat loss during isocapnic hyperventilation has been shown to give identical responses, we chose the latter provocational method in order to minimize increases in cardiac output that might interfere with the interpretation of mediator concentrations in arterial blood. Multiple aspects of pulmonary mechanics were also recorded before and after provocation. The results of these studies were then compared with the effects observed when the same subjects inhaled aerosols of specific antigens on the same day. Each challenge produced identical alterations in lung function, and neither was associated with consistent changes in arterial histamine. However, antigen provocation evoked a sustained and prolonged release of neutrophil chemotactic activity in each subject, whereas isocapnic hyperventilation with cold air was without effect. These data strongly suggest that mast-cell derived mediators are not involved in the development or maintenance of the bronchial obstruction that follows exercise in asthmatics.

Adult↗

Cold air inhalation and esophageal temperature in exercising humans.

This study was performed to examine the dynamics and localization of respiratory heat exchange in exercising humans breathing cold air. Eight normal individuals performed 10 min of exercise at 80% of their predicted Vo2max with inspired air at 22 degrees C, saturated with water vapor; or at -40 degrees C, dry. Rectal temperature (Tre) and temperature at various locations along the length of the esophagus were measured during the exercise period. Temperature in the lower third of the esophagus was in close agreement with Tre and was unaffected by the level of respiratory heat exchange. Upper esophageal temperature decreased substantially during exercise, the magnitude of the decrease being dependent upon proximity to intrathoracic airways and the level of respiratory heat exchange (RHE). We conclude that with high levels of RHE, the capacity of the nasopharynx and upper airways to completely condition inspired air is exceeded. As a consequence, heat and water exchange occur in regions of the respiratory tract not normally involved in this function.

Body Temperature↗

Role of respiratory heat exchange in production of exercise-induced asthma.

We have hypothesized that it is the total heat flux in the tracheobronchial tree during exercise that determines the degree of postexertional obstruction in asthma, and have developed quanititative expressions that relate these two events. We tested this hypothesis by comparing the observed responses to exercise, while our subjects inhaled dry air at various temperatures ranging from subzero to 80 degrees C in a random fashion, to those that we predicted would occur based upon calculations of respiratory heat exchange. We further determined if heat could be transferred from the inspired air to the mucosa so as to offset evaporative losses from the airways. The observed responses fell as air temperature was increased from -11 to +37 degrees C and exactly matched theoretical predictions. Above 37 degrees C, the observed response exceeded predictions, indicating that it was not possible to provide sufficient heat per se in the air to offset the vaporization of water. However, when small amounts of water vapor were added to the inspirate at high temperatures, bronchospasm was virtually abolished and the response again closely matched theoretical expectations. We conclude that the magnitude of exercise-induced asthma is directly proportional to the thermal load placed on the airways and that this reaction is quantifiable in terms of respiratory heat exchange.

Adult↗

Esophageal temperature during exercise in asthmatic and nonasthmatic subjects.

We measured the temperature in the rectum and two esophageal sites (retrocardiac and retrotracheal) during exercise in eight asthmatic and six normal subjects while they breathed air at subfreezing, ambient, and body conditions. Various aspects of pulmonary mechanics were recorded before and after exercise. The asthmatic subjects developed the greatest airway obstruction following exercise with cold air and no response at body conditions. There were no changes in pulmonary mechanics in the postexercise period in the normal individuals with any of the inspired air conditions. Despite these divergent mechanical responses retrotracheal temperatures fell by the same magnitude below core values in both groups of subjects, indicating that identical degrees of airway cooling occurred. We conclude that rather than having a defect in the ability to condition inspired air, asthmatic subjects are more responsive to the effects of incompletely conditioned air.

Adult↗

Rib cage deformation during static inspiratory efforts.

Patterns of rib cage (RC) deformation were studied in six normal subjects during moderate static inspiratory efforts such that esophageal pressure (Pes) as an index of transthoracic pressure fell to between -30 and -60 cmH2O during each maneuver. At lung volumes below 50% inspiratory capacity (IC), static inspiratory efforts deformed RC to a more elliptical shape; RC lateral diameter became smaller and RC lateral diameter became larger. However, at high lung volumes (greater than 50% IC) the opposite change in RC dimensions occurred despite similar changes in Pes, i.e., the RC became more circular. These differences in RC deformation did not appear to be a possive consequence of increased lung volume because the RC could be voluntarily deformed to a more circular shape at low lung volume when a) subjects performed static inspiratory efforts mainly with their intercostal and accessory muscles rather than their diaphragm as judged by a smaller change in transdiaphragmatic pressure for the same Pes; or b) subjects statically contracted their diaphragm with it held in a relatively flattened configuration as assessed by a large abdominal AP dimension. We suggest that deformation of the RC during static inspiratory efforts is not as predictable as has previously been suggested but depends on the pattern of contraction and configuration of the respiratory muscles.

Adult↗

Vagal effects on histamine, carbachol, and prostaglandin F2 alpha responsiveness in the dog.

To investigate whether an individual dog's responsiveness to histamine correlates with its responsiveness to other bronchoconstrictor agents and to investigate whether varying vagal effects account for the previously described range of histamine responsiveness, we compared dose-effect relationships of histamine to those of two pharmacological dissimilar agents, carbachol and prostaglandin F2 alpha before and after vagal blockade. There was a highly significant correlation between histamine and both carbachol (P less than 0.001) and prostaglandin F2 alpha (P less than 0.001) responsiveness. The range of responsiveness to prostaglandin F2 alpha was greater than that for histamine or carbachol. When histamine and carbachol were given simultaneously, a purely additive effect was found. Vagal blockade had no significant effect on histamine or carbachol responsiveness, but significantly diminished the responsiveness to prostaglandin F2 alpha; however, it neither narrowed the range nor changed the rank order of responsiveness. We conclude that the range of responsiveness is not specific for any one agent and that vagal mechanisms do not play a role in producing this range.

Airway Resistance↗

Pattern and mechanism of airway response to hypocapnia in normal subjects.

We examined the bronchoconstriction produced by airway hypocapnia in normal subjects. Maximal expiratory flow at 25% vital capacity on partial expiratory flow-volume (PEFV) curves fell during hypocapnia both on air and on an 80% helium- 20% oxygen mixture. Density dependence also fell, suggesting predominantly small airway constriction. The changes seen on PEFV curves were not found on maximal expiratory flow-volume curves, indicating the inhalation to total lung capacity substantially reversed the constriction. Pretreatment with a beta-sympathomimetic agent blocked the response, whereas atropine pretreatment did not, suggesting that hypocapnia affects airway smooth muscle directly, not via cholinergic efferents.

Adult↗

A critical assessment of the mechanism by which hyperoxia attenuates exercise-induced asthma.

Recent data demonstrate that the magnitude of the heat loss that occurs from the respiratory tract during exercise correlates with the degree of post-exertional obstruction that develops in asthmatics. Respiratory heat loss relates directly to the minute ventilation and heat capacity of the inspired gas and inversely to its water content and temperature. Because it has been shown that inhaling 100% oxygen during exercise blunts the obstructive response, we wondered if this effect could be accounted for by differing values of heat exchange with air and oxygen breathing. To examine this question, we studied 10 asthmatics by measuring multiple aspects of pulmonary mechanics before and after four bouts of exhausting leg work during which the subjects inhaled either air or oxygen conditioned to provide widely differing thermal burdens on their airways. Under all inspired gas conditions, oxygen breathing produced significantly less obstruction than air. Minute ventilation was also significantly less with oxygen as was the total heat lost. As the latter fell, so did the magnitude of the postexercise obstruction. When the differences in ventilation and respiratory heat loss between air and oxygen were eliminated by eucapnic hyperventilation, the differences in the obstructive responses also disappeared. Thus, the effects of hyperoxia on exercise-induced asthma can be accounteed for solely by alterations in heat exchange.

Adult↗

Apical fibrobullous disease with rheumatoid arthritis.

We describe a patient who developed noninfectious apical fibrobullous disease 12 years after the diagnosis of seropositive, nodular, deforming rheumatoid arthritis. Fibrobullous disease of the pulmonary apices is a rare entity that is usually found in association with ankylosing spondylitis. Its appearance with rheumatoid arthritis has not been reported. Speculative factors which may predispose to apical fibrobullous disease, such as a stiff chest wall, impaired esophageal motiligy, and HL-A antigen B27, were not present in our patient.

Adult↗

Bilateral diaphragmatic paralysis with hypercapnic respiratory failure. A physiologic assessment.

Bilateral diaphragmatic paralysis was suspected in a patient presenting with hypercapnic respiratory failure who exhibited paradoxic (i.e., inward) abdominal movement on inspiration during tidal breathing in the supine posture; no paradoxic abdominal motion was observed at the bedside with the patient upright. Transdiaphragmatic pressure measurements established the diagnosis of diaphragmatic paralysis, although 20 cm H2O pressure developed across the diaphragm during the latter part of a forced expiration, presumably due to the development of passive tension in the diaphragm as it was stretched near residual volume. Analysis of the relative motion of the rib cage and abdomen during breathing by the use of magnetometers confirmed the presence of abdominal paradox throughout the breathing cycle when the patient was supine, and established that paradoxic motion of the abdomen also occurred when the patient was in the erect posture but only in the latter half of inspiration. Our findings confirm that the use of transdiaphragmatic pressure measurements and magnetometry will help to quantify diaphragmatic function, that passive tension develops in the paralyzed diaphragm near residual volume and should not be confused with active contraction, and that paradoxic motion of the abdomen may be masked from the clinician when the patient is erect.

Aged↗

Effects of prostaglandin F2alpha on lung mechanics in nonasthmatic and asthmatic subjects.

Prostaglandins have been implicated as secondary pharmacologic mediators in allergic bronchial asthma. We have studied the effects of the intravenous infusion of prostaglandin F2alpha (PGF2alpha) on pulmonary mechanics in nonasthmatic and asthmatic volunteers. Before and during the infusion, measurements were made of total lung capacity and its subdivisions, static deflational transpulmonary pressure-volume relationships (PV), and maximal expiratory flow-volume curves with air and after a washing of an 80% helium-20% oxygen mixture. In both groups, PGF2alpha caused significant decreases in vital capacity and maximal flow and increases in residual volume. There were not significant differences between groups in either the absolute magnitude or the percent change in the variables, a result which may have been due to the similarity of the pulmonary mechanics in both groups prior to infusion. Changes in density dependence were bidirectional in both groups, indicating that relative contributions of large and small airways to flow limitation changed differently among individuals. The single between-group difference in responses noted was a leftward shift of the PV curve in the asthmatics, suggesting recoil of the lung which occurs in asthma.

Adult↗