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Biomedical subjects

A Wanner

Publications and source records attributed to A Wanner.

At least 163 records · Page 9Linked to original sources

Role of H1- and H2-receptors in airway reactions to histamine in conscious sheep.

We investigated the role of histamine H1- and H2-receptors in the control of airway function in six conscious sheep. In five of these, inhalation of histamine (combined H1- and H2-receptor stimulation) caused an increase in pulmonary resistance (RL) and functional residual capacity and had a variable effect on distribution of ventilation as measured by N2-clearance delay. Pretreatment with the H1-antagonist, chlorpheniramine, prevented these functional effects of histamine challenge, whereas pretreatment with the H2-antagonist, metiamide, potentiated the effects of histamine on RL and caused a uniform increase in N2-clearance delay. Pretreatment with both chlorpheniramine and metiamide prevented the effects of histamine on all parameters indicating effective blockade of H1- and H2-receptors at the dosages used. In one sheep, an increase in RL and N2-clearance delay in response to histamine was only observed after metiamide pretreatment. With or without pretreatment, histamine failed to alter the static pressure-volume curve of the lung. We conclude that in conscious sheep a) inhalation of histamine produces bronchoconstriction and pulmonary hyperinflation without changing lung elastic recoil, b) the observed effects of histamine are mediated by H1-receptors, and H2-receptors have a modulating role, and c) variable effects of histamine on RL and distribution of ventilation may be related to differences in the distribution of H1- and H2-receptors in central and peripheral airways.

Aerosols↗

Clinical indications for and effects of bland, mucolytic, and antimicrobial aerosols.

The clinical usefulness of bland, mucolytic, and antimicrobial aerosols in the management of obstructive airway disease or bronchopulmonary infections was critically reviewed at th last Conference on th Scientific Basis of Respiratory Therapy in 1974. From the information available at that time, it was cocluded that there was little scientific basis for these therapeutic modalities. It was also suggested that the value of aerosol therapy should be evaluated by objective tests. The relatively few studies reported during the last 5 years have not generated new data in support of such aerosol therapy. Three criteria have been used to assess the efficacy of bland and mucolytic aerosols: respiratory function, mucociliary function, and subjective symptoms. Although respiratory and mucociliary function have generally been found to remain unaltered or to deteriorate after administration of bland or mucolytic aerosols, some investigators have observed facilitated expectoration or improved cough efficiency. The effectiveness of antimicrobial aerosols is more difficult to evaluate, and their value in patients with bacterial or fungal pulmonary infections remains to be demonstrated. Considering the cost and potential hazards of aerosol therapy, its use should be restricted to forms of aerosols whos clinical value has been objectively demonstrated; a reassessment of the literature suggests that bland and currently used mucolytic and antimicrobial aerosols do not meet this requirement.

Adult↗

The role of mucociliary dysfunction in bronchial asthma.

Abnormalities of mucociliary function in the airways of patients with bronchial asthma are suggested by the clinical observation of excessive tracheobronchial secretions which are difficult to expectorate and may contribute to bronchial obstruction. Pathologic and functional studies in animals and patients have demonstrated an impairment of mucociliary transport mechanisms, but the pathogenesis of this abnormality is still poorly understood. In patients with allergic asthma, the elaboration of chemical mediators in the lung seems to depress mucociliary function. Although pharmacologic agents which increase mucous transport rates have been identified, more potent stimulators will probably be needed to produce a clinical improvement in patients with bronchial asthma.

Animals↗

Antigen-induced bronchospasm in conscious sheep.

In 10 conscious ewes with cutaneous sensitivity to Ascaris suum, measurements of pulmonary resistance (RL), static lung compliance (Cst), functional residual capacity (FRC), and arterial blood gas composition along with arterial plasma histamine concentration (H) were obtained before and after inhalation challenge with A. suum extract. Five animals showed no changes in respiratory mechanics after A. suum challenge; in these H did not change. The remaining five animals responded to A. suum challenge with bronchospasm reflected by the following maximum changes in mean values that were significant 15 and 30 min after beginning of challenge, respectively: RL 248% , FRC 126%, specific pulmonary conductance 33%, and arterial PO2 63% of base line. These parameters returned towards base line by 120 min. No changes occurred in Cst, arterial PCO2, and pH. Five minutes after beginning of A. suum challenge, mean H was increased to 423% of base line with a return to base line 10 min later. In the same 5 animals, no changes were observed in pulmonary function or H after inhalation of ragweed extract (control). These results suggest that antigen-induced bronchospasm in sensitized conscious sheep represents an anaphylactic airway response and shares distinct physiological features with human bronchial asthma including pulmonary hyperinflation.

Airway Resistance↗

Determination of pulmonary blood flow by the rebreathing technique in airflow obstruction.

To test the hypothesis that the effect of nonuniform gas distribution on the uptake of inhaled soluble gases in the lung is minimized by rebreathing, we measured pulmonary blood flow by the thermodilution technique, and pulmonary capillary blood flow, combined pulmonary tissue and capillary blood volume, diffusing capacity of the lung for CO, and alveolar volume by a rebreathing technique in conscious sheep before and immediately after inhalation of a histamine aerosol (4% solution). We also measured pulmonary resistance, distribution of ventilation by multiple-breath N2 washout, and arterial blood gases to monitor airway responses. Histamine inhalation produced a mean pulmonary resistance increase to 621% of baseline accompanied by uneven distribution of ventilation and a decrease in arterial Po2. Despite these alterations in airway function, there were no concomitant changes in pulmonary capillary blood flow, combined pulmonary tissue and capillary blood volume, diffusing capacity of the lung for CO, alveolar volume, or the ratio of diffusing capacity for CO to alveolar volume. Mean pulmonary capillary blood flow and pulmonary blood flow did not differ from each other before and after histamine inhalation. We conclude that the rebreathing technique for noninvasive measurement of pulmonary hemodynamics is satisfactory in the presence of airflow obstruction.

Airway Obstruction↗

Distribution of ventilation in normal children.

Measurements of closing volume and the distribution fo ventilation by both single-breath (SBN2) and multiple-breath nitrogen washout methods were obtained in 376 healthy boys and girls, ages 6 to 18 years. A closing volume could be demonstrated in 39 percent of the subjects, and closing volume expressed as percentage of vital capacity did not change with height. Closing capacity expressed as percentage of total lung capacity showed a slight decrease with height. The slope of phase III of the SBN2 curve decreased with height. Single compartment N2 washout curves were observed in 72 percent of the subjects, and the incidence of single compartment curves increased with age. In those subjects with two compartment N2 washout curves, the relative compartmental ventilation became more even with increasing height. Our observations suggest that parallel units among peripheral airways grow at different rates.

Adolescent↗

Respiratory mechanics in conscious sheep: response to methacholine.

Most currently used animal models of allergic airway diseases differ from human asthma in that induced bronchospasm in the former is not accompanied by pulmonary hyperinflation. In the present investigation, we chose unsedated, restrained sheep to determine the effect of cholinergic bronchial provocation on respiratory mechanics, functional residual capacity (FRC), and arterial blood gases. Seven animals had been actively sensitized by intramuscular injections of Ascaris suum extract, and four untreated animals served as controls. After inhalation of nebulized 1% methacholine solution, mean pulmonary resistance increased significantly in the sensitized sheep from a base line of 2.4 +/- 0.7 (SD) cmH2O/(l/s) to a peak value after 5 min of 7.9 +/- 4.0 cmH2O/(l/s). This was accompanied by a significant increase of mean FRC from 0.99 +/- 0.14 liters to 1.31 +/- 0.24 liters. The observed changes were transient, and after 60 min, pulmonary resistance and FRC had returned to base-line values. No significant changes occurred in static lung compliance, PaO2, PaCO2, and pH. In the control animals, methacholine provocation did not produce changes in pulmonary function. These results indicate that, in sensitized conscious sheep, induced bronchospasm is associated with pulmonary hyperinflation.

Animals↗

Effects of sulfuric acid aerosol on cardiopulmonary function of dogs, sheep, and humans.

Submicronic aerosol of sulfuric acid (H2SO4) originates from the burning of fossil fuels and discharge of vapor from the automobile engine equipped with the catalytic converter. This study was conducted to determine whether brief exposure to this aerosol in high concentrations adversely affects the cardiopulmonary system. In all studies, submicronic aerosol of sodium chloride was used as a control. Anesthetized dogs that breathed H2SO4 aerosol in concentrations up to 8 mg per m3 showed no effects on respiratory resistance, static lung compliance, and functional residual capacity. A 4-hour exposure to H2SO4 aerosol (4 mg per m3) produced no significant changes in mechanics of breathing, functional residual capacity, pulmonary and systemic arterial blood pressures, cardiac output, heart rate, and arterial blood gas tensions. Conscious sheep that breathed H2SO4 aerosol in concentrations up to 14 mg per m3 for 20 min had no alteration of tracheal mucous velocity in an immediate 3-hour follow-up period or 5 to 10 days later. Conscious sheep that breathed H2SO4 aerosol (4 mg per m3) for 4 hours had no significant alteration of tracheal mucous velocity immediately and 2 hours thereafter. Both normal and asthmatic adults breathing H2SO4 aerosol in concentrations up to 1 mg per m3 for 10 min showed no significant alteration of lung volumes, distribution of ventilation, ear oximetry, dynamic mechanics of breathing, oscillation mechanics of the chest-lung system, pulmonary capillary blood flow, diffusing capacity, O2 consumption, and pulmonary tissue volume. No delayed effects in pulmonary function nor exacerbation of bronchial asthma were observe during a follow-up period of a few weeks. The present study indicates that single exposure to submicronic H2SO4 aerosol does not produce an immediate or a delayed adverse effect on cardiopulmonary function in anesthetized dogs, conscious sheep, and normal and asthmatic adults.

Aerosols↗

Mucociliary transport in allergic patients with antigen-induced bronchospasm.

Tracheal mucous velocity (TMV) and respiratory mechanics were measured in asymptomatic asthmatic patients with ragweed hypersensitivity before and after inhalation of specific antigen, and with or without cromolyn sodium pretreatment. TMV was measured radiographically, and the airway response to bronchial provocation was monitored by measurements of forced expiratory volume in one sec and specific airway conductance. TMV was significantly less (6.3 +/- 2.3 mm per min, mean +/- SD) in the 6 asymptomatic asthmatic patients than in 7 normal subjects (11.6 +/- 3.6 mm per min, mean +/- SD). In the asthmatic patients, mean TMV diminished to 72 per cent of baseline immediately after bronchial provocation when specific airway conductance was decreased to 65 per cent of baseline or less, with a further decrease in TMV to 47 per cent of baseline after one hour, at which time respiratory mechanics had returned to baseline values. Pretreatment with cromolyn sodium prevented the decrease in TMV after bronchial provocation. We concluded that in asymptomatic patients with allergic asthma, (1) baseline TMV is impaired, (2) inhalation of specific antigen causes a marked decrease in TMV independent of the degree of bronchospasm, and (3) the decrease in TMV may be related to the release of chemical mediators.

Adolescent↗

Failure of hypoxic pulmonary vasoconstriction in the canine asthma model. Effect of prostaglandin inhibitors.

Measurements of respiratory mechanics, arterial blood gases, and pulmonary vascular resistance were made before and 15 min after inhalation challenge with Ascaris suum extract in dogs with natural sensitivity to this antigen. 25 of 47 dogs were treated before inhalation challenge with a prostaglandin inhibitor (90 mg/kg of aspirin or 2 mg/kg of indomethacin by intravenous infusion). In response to the challenge, bronchospasm developed in approximately half (responders) of each group reflected by decreases in mean specific respiratory system conductance and arterial oxygen tension. While the dogs were breathing room air, pulmonary vascular resistance remained unchanged after antigen challenge in the responders not given aspirin or indomethacin, but increased significantly and was associated with a lesser degree of arterial hypoxemia in the responders pretreated with either of the prostaglandin inhibitors. Prevention of arterial hypoxemia by oxygen breathing blocked an increase in pulmonary vascular resistance in four pretreated responders. No changes in respiratory mechanics, pulmonary hemodynamics, or arterial blood gases were noted in the 21 dogs who did not develop bronchospasm regardless of whether or not they were pretreated. 12 additional dogs in whom arterial hypoxemia was produced by 10% oxygen breathing, showed an increase in pulmonary vascular resistance that was not potentiated by pretreatment with aspirin in 6. We conclude that in acute experimental canine asthma, vasodilator prostaglandins appear to blunt the hypoxic pulmonary vasoconstrictor response, thereby further compromising gas exchange but preventing the development of pulmonary hypertension.

Animals↗

Accuracy of Drager and Wright ventilation meters.

Simple compact mechanical ventilation meters for bedside monitoring are in wide-spread use in this country. We investigated the accuracy of two such ventilation meters, the Drager Volumeter and the Wright Respirometer. Volume measurements on 16 units were made at fixed flow rates between 6 and 12 l/min. Both types of spirometer showed similar magnitudes and patterns of inaccuracy. For 14 used units, the mean deviation from the actual value was the smallest between the flow rates of 15 and 30 l/min, with a mean systematic underestimation of about 15 per cent and maximum variability among individual units (S.D. 10--12 per cent) at lower flow rates. Measurements at flow rates above 120 l/min were unsatisfactory due to locking of the ventilation meter mechanism. The single new Drager Volumeter tested was relatively accurate at all flow rates measured, whereas the single new Wright Respirometer tested showed inaccuracies comparable to the mean values of the used units. We conclude that these devices are satisfactory to monitor patients on continuous mechanical ventilation but may not be adequate for bedside spirometry.

Evaluation Studies as Topic↗

Volume characteristics of extra- and intraparenchymal segments of the canine pulmonary artery.

The volumes of the extraparenchymal segment (VpaEP) and intraparenchymal segment (VpaIP) of the pulmonary arterial tree were determined in intact anesthetized dogs during room air breathing and acute hypoxia. Total pulmonary arterial blood volume (Vpatotal) was calculated as the product of pulmonary blood flow and pulmonary arterial circulation time. An angiographic technique was used to estimate VpEP. VpaIP was calculated by subtracting VpaEP from Vpatotal. During room air breathing at functional residual capacity, mean +/- SD of VpaEP was 17.1 +/- 5.1 ml and of VpaIP was 31.7 +/- 20.8 ml, representing 40% and 60%, respectively, of Vpatotal. Vpatotal increased 22.2 +/- 10.5 ml during lung inflation, with proportional increases in VpaIP and VpaEP. VpaEP was found to be influenced equally by changes in transmural pulmonary arterial and transpulmonary pressures. Acute hypoxia was accompanied by an increase in pulmonary vascular resistance and a decrease in volume distensibility of the extraparenchymal segment. Vpatotal increased 76% without changes in the relative volume distribution of VpaEP and VpaIP. These findings can be best explained by active vasomotion with an increase in down-stream pulmonary vascular resistance.

Animals↗

Continuous measurement of respiratory resistance in asthmatic children.

In 13 children (7-13 years old) with bronchial asthma in remission, respiratory system resistance was continuously measured by the forced oscillation method at 10 Hz, using on-line digital computer analysis. Corrections were made for mouth impedance which was determined from a prior Valsalva maneuver. Functional residual capacity was also periodically determined by the body plethysmographic technique in order to allow calculation of specific respiratory system conductance (SGRS). The total observation period of 45 min consisted of quiet breathing interrupted by vital capacity maneuvers. In a single-blind design, eight children were given 0.15 mg isoproterenol sulfate from a proprietary spray delivered in the beginning of an inspiratory vital capacity maneuver while five received a placebo (freon propellent alone). A significant increase in SGrs (+53%) was observed 75 sec after isoproterenol sulfate administration. SGrs peaked after 2 min (+ 61%) and remained elevated significantly for 10 min. No significant changes occurred in the placebo group. The immediate decrease in SGrs which was observed following control vital capacity maneuvers, was prevented by isoproterenol sulfate but not by the freon propellent. Our findings suggest that although peak bronchodilation does not occur before 2 min following isoproterenol sulfate inhalation, an effect, namely prevention of bronchoconstriction induced by a deep breath, is already detectable within seconds.

Adolescent↗