Subject(s)
Cheyne-Stokes Respiration/therapy , Heart Failure/physiopathology , Positive-Pressure Respiration , Sleep Apnea, Central/therapy , Cheyne-Stokes Respiration/complications , Endpoint Determination , Exercise Tolerance , Heart Failure/complications , Humans , Sleep Apnea, Central/complications , Stroke Volume , Survival Rate , Time , Treatment OutcomeABSTRACT
Effects of experimental exposure to O3 (0.33 ppm) or filtered air on regional lung function were assessed in nine healthy male subjects. Immediately after 2-h chamber exposures, regional ventilation and particle dosimetry were measured by gamma camera imaging. The vertical distributions of a radiolabeled gas (133Xe) and aerosol (3.5-microns-diam insoluble 99mTc-tagged Fe2O3 particles) were quantitated for upper, middle, and lower lung regions; distribution data were corrected for regional differences in lung volume and tissue attenuation. Indexes of mechanical function, inspiratory capacity, and mid-maximal expiratory flow rates were significantly reduced after O3, but functional residual capacity remained unchanged. Exposure to O3 significantly enhanced the fraction of respired aerosol retained by the lung and altered the distribution pattern of deposited aerosol by increasing particle deposition to the middle lung region (P < 0.05). Aerosol penetration indexes, i.e., ratio of particle deposition in central lung regions to that in peripheral lung regions, and particle retention 24 h postinhalation (an index of aerosol deposition within alveoli and slowly clearing bronchioles) indicated that particle filtration efficiency had increased for tracheobronchial and parenchymal lung regions. For seven of the nine subjects, regional ventilation after O3 was reduced by 14% to the lung base and enhanced by 8 and 6% to the upper and middle lung regions, respectively; these changes were significant (P < 0.02) compared with ventilation after filtered air.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Lung/drug effects , Ozone/pharmacology , Adult , Aerosols , Gamma Cameras , Humans , Lung/diagnostic imaging , Lung Volume Measurements , Male , Maximal Midexpiratory Flow Rate , Particle Size , Radionuclide Imaging , Respiratory Function Tests , Technetium , Xenon RadioisotopesABSTRACT
The influence of aerosolized atropine sulfate on airway tone was evaluated in nine healthy adult subjects using three modes of inhalation and a dosimeter to deliver equal doses of aerosol. For six of the subjects additional studies with radioaerosols and scintillation scans were accomplished to qualify lung distributions of deposited aerosol. The three breathing patterns, identified as Tidal, IC, and VC, had average inspiratory volumes of 0.66 +/- 0.1, 2.10 +/- 0.4, and 4.31 +/- 0.9 (SD) L and were initiated from the rest position of the lung for the first two patterns, and residual volume for the third pattern. Total nebulization time and concentration inhaled were identical for each pattern at an atropine dose of 0.025 mg/kg body weight. Average inspiratory flow rates had means of 0.40 +/- 0.1, 0.64 +/- 0.2, and 0.82 +/- 0.2 (SD) L/s for the respective inhalations. Functional indices of FEV1, MMF, and Vmax50 and anticholinergic side effects were assessed for a 4-h period after aerosol administration. Functional improvement and duration of effect were maximal with the IC pattern. Within the first hour, absolute increases in FEV1 averaged 240 ml above baseline (6.2% increase). Increases for MMF and Vmax50 were on average greater than 23% above baseline (airflow benefit exceeded baseline by 0.91 +/- 0.4 L/s for MMF and 1.14 +/- 0.4 L/s for Vmax50). Except for xerostomia, which was present after all patterns, systemic side effects (tachycardia, blurred vision, and urinary retention) occurred only with VC pattern.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Atropine/administration & dosage , Bronchi/innervation , Lung/metabolism , Pulmonary Ventilation , Vagus Nerve/physiology , Administration, Inhalation , Adult , Aerosols , Atropine/pharmacology , Female , Humans , Lung/diagnostic imaging , Male , Pulmonary Ventilation/drug effects , Radionuclide Imaging , Technetium Tc 99m Sulfur Colloid , Vagus Nerve/drug effectsABSTRACT
The influence of aerosolized atropine sulfate on lung airway mucus clearance was investigated in healthy human subjects who were nonsmokers. Mucus transport was measured with radiolabeled insoluble particles inhaled by mouth and deposited onto mucosal surfaces; subsequent retention of radiolabel was quantitated over a 4- to 5-h period by a noninvasive, posteriorly aligned, gamma camera. Placebo and atropine clearance tests were matched in a given subject for initial and for final (24-h postinhalation) deposition pattern of labeled aerosol at the onset and conclusion, respectively, of tracheobronchial particle clearance. In seven subjects mucociliary function was delayed after inhalation of 0.025 mg/kg body weight atropine sulfate as compared with placebo (0.9% NaCl). On the basis of the area under the activity versus time curves, retention times during atropine exceeded placebo times by more than 30% (p less than 0.01). At 90 min postatropine inhalation, the Vmax50 exceeded baseline values by 21% (p less than 0.01). Urine retention was present in one subject and xerostomia was present in all subjects after atropine. These data suggest that a single dose of atropine sulfate delivered topically to the airway surfaces delays the continuous flow of airway mucus in healthy subjects and that basal autonomic tone is an inherent factor for optimal secretion and/or removal of tracheobronchial secretions.
Subject(s)
Atropine/administration & dosage , Lung/drug effects , Mucociliary Clearance/drug effects , Administration, Inhalation , Adult , Aerosols , Female , Forced Expiratory Volume/drug effects , Forced Expiratory Volume/physiology , Humans , Lung/diagnostic imaging , Lung/physiology , Male , Mucociliary Clearance/physiology , Radionuclide Imaging , Reference Values , Technetium Tc 99m Sulfur Colloid , Time Factors , Vital Capacity/drug effects , Vital Capacity/physiology , Xenon RadioisotopesABSTRACT
Previous investigators, using 99mTc-DTPA aerosol as a marker to assess epithelial permeability in asthma, did not find an increased permeability in this group. However, they either failed to deliver the aerosol to the optimal site (bronchial mucosa, not alveoli) or failed to account for mucociliary clearance in analyzing their results. We studied 10 asthmatics and eight age-matched control subjects using a dosimeter (Spira-Elektra 2) and a carefully controlled breathing pattern to deliver aerosol to the subjects' airways. Two aerosols were delivered on separate days in each patient; 99mTc-DTPA aerosol, and 99mTc-HSA (human serum albumin), using similar breathing patterns to ensure reproducibility of the deposition pattern with the two aerosols. From measurements of retention versus time over a 1-h period, rate constants Ktot and Km were determined for the clearance of 99mTc-DTPA and 99mTc-HSA, respectively. By modelling the airways as a single compartment with two possible routes of clearance, we determined the permeability rate constant, Kp, as Ktot minus Km. There was no significant difference between Ktot in normal subjects and asthmatics; however, because of the slower mucociliary clearance in the asthmatic group, and the relative importance of mucociliary clearance in determining the washout of 99mTc-DTPA aerosol, there was a significant difference in airway permeability between the normal subjects and the asthmatics (t1/2 = 296 min +/- 141 SD and 126 min +/- 58, p less than 0.01, in normal subjects and asthmatics, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
