Inhaled Atropine Sulfate Research Articles

Cardiopulmonary Responses to Exercise in Chronic Airflow Obstruction: Effects of Inhaled Atropine Sulfate

The purpose of this study was to evaluate the effects of inhaled atropine sulfate on the exercise capacity and cardiopulmonary responses to exercise in patients with chronic airflow obstruction (CAO). Eighteen patients underwent duplicate incremental (15 watts/min) maximal cycle ergometer exercise tests 60 minutes after either inhaled atropine (0.075 mg/kg) or placebo, in double blind randomized fashion on consecutive days. Bronchodilator medications were withheld before each study. Spirograms were obtained before and 60 minutes after each aerosol treatment. Atropine increased the FEV1 by 25 percent, from 1.37 +/- 0.49 to 1.71 +/- 0.52 L (p less than 0.001), as compared to placebo. Although the ventilation at exhaustion (VEmax) increased significantly (from 52.3 +/- 11.5 to 55.9 +/- 10.0 L/min, P less than 0.05) after atropine, the increase in the mean maximum work load (95 +/- 28 vs 101 +/- 19 watts) did not achieve significance. The drug resulted in a significant decrease in oxygen consumption at all equivalent workloads greater than "0" watts (unloaded cycling), presumably because the improvement in airway mechanics decreased the oxygen cost of ventilation. Atropine-induced increases in FEV1 did not result in a significant group mean increase in maximum exercise capacity, but the drug did result in a lower oxygen cost of performing work in patients with CAO.

Central and local cholinergic components of histamine-induced bronchoconstriction in dogs.

To determine the importance of central and local reflexes in the bronchoconstriction produced by inhaled aerosolized histamine, chloralose-urethan-anesthetized dogs were intubated with a double-lumen catheter, ventilated with a dual cylinder respirator, and instrumented for the measurements of pulmonary conductance (GL) and dynamic compliance (Cdyn) in each lung. In each dog, dose-response curves to inhaled aerosolized histamine were obtained in both lungs separately but synchronously. Four series of experiments were performed. In the first series (n = 10) the responses of the right and left lungs were compared and found to be approximately equal, indicating that one lung could be used as a control for the other. In the second and third series the dose-response curve of one lung that had either been treated with inhaled atropine sulfate (n = 6) (4 mg/ml) or vagotomized (n = 4) was compared with the contralateral control lung. At low concentrations of histamine, GL and Cdyn decreased more in the control lungs than in their atropine-treated or vagotomized counterparts, and approximately 40% of the bronchoconstriction induced was reflex in origin. At higher concentrations of histamine the responses of the control and atropine-treated or vagotomized lungs were not significantly different. In the fourth series of experiments (n = 6) histamine dose-response curves were obtained following combined bilateral vagotomy and unilateral delivery of inhaled aerosolized atropine. In these dogs GL, but not Cdyn, fell to a greater extent in the control than in the atropine-treated lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromuscular response to resistive unloading: helium vs. bronchodilation.

To evaluate the neuromuscular response to resistive unloading, we compared the ventilatory and occlusion pressure (P100) response of normal subjects breathing 20.9% O2 in helium (He-O2) with their response to unloading produced by inhaled atropine sulfate. During He-O2 breathing airway resistance (Raw) fell by 49% of the base-line value on air, and P100 decreased by 20.8%. Minute ventilation, tidal volume, respiratory frequency, end-tidal Pco2, inspiratory and expiratory duration, and mean inspiratory flow were not significantly different when air was replaced by He-O2. In contrast, although atropine reduced Raw by an equivalent amount, there was no change in P100. Atropine had no significant effect on other respiratory variables, although a trend toward higher minute ventilation was noted. Fowler dead space increased after atropine but was not affected by He-O2. We conclude that, unlike He-O2 unloading, atropine unloading does not cause a reduction in occlusion pressure. This may be due to the effect of atropine on anatomical dead space which stimulates ventilation sufficiently to offset the fall in neuromuscular output due to resistive unloading.

Atropine and Terbutaline Aerosols in Chronic Bronchitis: Efficacy and Sites of Action

To examine the additive properties and the sites of action of inhaled atropine sulfate (0.05 mg/kg of body weight) and terbutaline sulfate (0.005 mg/kg) in patients with chronic airflow obstruction, we tested these aerosols separately and together in a double-blind random sequence. Twelve patients with chronic bronchitis and perennial obstruction of airflow were studied by measuring three indices of efficacy (specific airway conductance [Gaw/VL], the forced expiratory volume in one second [FEV1] and the forced vital capacity [FVC]) and three indices of the site of action within the airway (delta [(Gaw/VL)/FEV1], the difference between the change in forced expiratory flow at 75 percent of vital capacity and the change in forced expiratory flow at 25 percent of vital capacity, and the change in density dependence of maximal airflow at 50 percent of vital capacity). Both atropine and the combination of atropine and terbutaline improved all indices of efficacy significantly more than did terbutaline. With individual exceptions, the addition of terbutaline to atropine improved Gaw/VL but not forced airflow. All measures of site of action suggested an advantage for atropine in relatively proximal airways. These results indicate that combined therapy with beta-adrenergic and anticholinergic bronchodilator drugs is marginally more effective than therapy with atropine alone in these patients and suggest that anticholinergic aerosols dilate larger airways more effectively than the beta-agonists.

Atropine and Exercise-Induced Bronchoconstriction

Six asthmatic children were studied to determine whether supplemental, parenteral atropine would increase the effects of bronchodilation and protection against exercise-induced bronchoconstriction after maximal effects had been achieved by inhalation. First, we determined the amount of inhaled atropine sulfate that would give maximal bronchodilation for each patient at rest. This quantity of atropine was designated as "A." Then all subjects exercised for five sessions with the following pre-exercise treatments in a random order: (a) inhaled distilled water plus intramuscular (IM) saline solution; (b) inhaled A dose of atropine plus IM saline solution; (c) inhaled distilled water plus 0.35 mg IM atropine; (d) inhaled A dose of atropine plus 0.35 mg IM atropine; and (e) inhaled double the A dose plus IM saline solution. The results showed that the combination of inhaled and IM atropine had the greatest bronchodilation effect and the greatest protection against exercise-induced bronchoconstriction. Atropine inhalation alone (A dose) or IM injection (0.35 mg) was not as effective in bronchodilation or in alleviation of exercise-induced bronchoconstriction. Doubling the dose of inhalation (2A) did not increase the effects of the A dose. These results support the hypothesis that inhaled atropine does not reach all the airways where cholinergic receptors are present.

Inhaled atropine sulfate in acute asthma.

We administered inhaled atropine sulfate to acute asthmatics already receiving therapeutic doses of adrenergic agonists, theophylline, and corticosteroids. Following atropine, hyperinflation diminished whereas vital capacity and expiratory flow rates breathing air and helium-oxygen increased (p less than 0.025 - p less than 0.005). Initial density dependence correlated inversely with changes in density dependence after atropine (r = -0.69, p less than 0.001). We conclude that: (1) inhaled atropine sulfate was effective therapy for acutely ill asthmatics already being treated with multiple antiasthmatic agents; (2) atropine caused large and peripheral airways bronchodilatation, and (3) the predominant site of bronchodilatation after atropine was related to the site of flow limitation before atropine.

Atropine-Induced Psychosis: An Unusual Complication of Therapy with Inhaled Atropine Sulfate

An acute organic brain syndrome occurred in a patient being treated with inhaled atropine sulfate. Immediate reversal of the patient's mental status was achieved with intravenous administration of physostigmine.

Lower threshold and greater bronchomotor responsiveness of asthmatic subjects to sulfur dioxide.

To determine whether subjects with mild asthma or seasonal rhinitis have greater bronchomotor responses to sulfur dioxide (SO2) than normal subjects, we undertook a study in 7 asthmatic, 7 atopic, and 7 normal subjects, 23 to 37 yr of age. We measured the change in specific airways resistance (SRaw) provoked by 10 min of breathing 1, 3, and 5 ppm of SO2 delivered by mouthpiece on separate days at least 48 h apart. To assess the significance of parasympathetic pathways in the bronchomotor responses to SO2, we also measured the change in SRaw provoked by 5 ppm of SO2 in 17 of the subjects after they inhaled atropine sulfate aerosol (0.1 mg/kg). We found that in the asthmatic subjects, SRaw increased only at 5 ppm. In the asthmatic group, SRaw increased more than in either of the other groups at 5 ppm (p < 0.005), and was sometimes associated with marked dyspnea requiring bronchodilator therapy. The increases in SRaw produced by inhalation of SO2 were prevented by treatment with atropine in asthmatic and nonasthmatic subjects, which suggested the involvement of parasympathetic pathways. These results indicated that subjects with mild asthma develop bronchoconstriction after exposure to concentrations of SO2 well below currently accepted standards for occupational exposure, and that SO2-induced bronchoconstriction is mediated by parasympathetic pathways.