methylatropine and Hypoxia

Adrenergic bronchodilators have the potential drawback that they may increase hypoxemia in spite of relieving air-flow obstruction in patients with asthma. Anticholinergic bronchodilators are of interest as alternatives to beta-adrenergic agents, particularly in patients with chronic bronchitis and emphysema, yet little is known of the effects of either class of agent on gas exchange in patients with this diagnosis. We compared their effects on gas exchange in 12 patients with chronic bronchitis and emphysema who also had arterial hypoxemia in a double-blind crossover study. We found that nebulized atropine methonitrate, a quaternary ammonium anticholinergic bronchodilator, resulted in only minor and statistically insignificant effects on gas exchange at all times for as long as 60 min after its inhalation. In contrast, the beta-adrenergic bronchodilator metaproterenol hydrochloride resulted in a statistically significant decrease in the PaO2, the greatest mean decrease being 5.0 +/- 2.5 mm Hg (mean +/- 1 SD). The effects of metaproterenol on arterial blood gases in this population of patients were more prolonged than those previously reported in asthmatic subjects with lesser degrees of hypoxemia. An anticholinergic bronchodilator might be preferable in patients with hypoxemia caused by chronic bronchitis and emphysema in that it does not carry the risk of worsening systemic hypoxemia.

Topics: Aged; Atropine Derivatives; Bronchodilator Agents; Carbon Dioxide; Forced Expiratory Volume; Humans; Hypoxia; Lung Diseases, Obstructive; Metaproterenol; Middle Aged; Oxygen; Pulmonary Gas Exchange

Lung resistance may be influenced by chemoreceptor activity and modulated by inspiratory neural output; however, it is unknown whether the contractile elements of lung tissue participate in these changes during early development. In anesthetized paralyzed open-chest piglets, we measured phrenic electroneurogram, lung resistance (RL), and tissue resistance utilizing alveolar capsules to partition the hypercapnic and hypoxic responses of RL into tissue (Rti) and airway resistance (Raw) components. Inhalation of 7% CO2 significantly increased RL (7.4 +/- 0.5 to 11.3 +/- 0.6 cmH2O.l-1.s), Rti (5.2 +/- 0.5 to 6.9 +/- 0.5 cmH2O.l-1.s), and Raw (2.2 +/- 0.2 to 4.4 +/- 0.4 cmH2O.l-1.s). Inhalation of 12% O2 caused more modest increases in RL, Rti, and Raw. Oscillations in tracheal and alveolar pressures appeared in synchrony with phrenic activity in response to both chemoreceptor stimuli. Cholinergic blockade eliminated these oscillations and significantly reduced the hypercapnic and hypoxic responses of RL, Rti, and Raw. These data demonstrate for the first time that hypercapnia and hypoxia elicit a cholinergically mediated increase in Rti which, just like the airway component of RL, is modulated by inspiratory neural output and is present during early development. Such coordination in neural function throughout the respiratory system may serve to optimize gas exchange during early postnatal life.

Topics: Airway Resistance; Animals; Animals, Newborn; Atropine Derivatives; Blood Gas Analysis; Female; Hypercapnia; Hypoxia; Lung; Male; Parasympatholytics; Phrenic Nerve; Pulmonary Gas Exchange; Swine

The sustained increase in ventilation (V1) that occurs during acute hypoxemia in adults is not characteristic of the neonate as V1 falls to or below baseline values soon after onset of the hypoxic stimulus. Associated with this decline in V1 is a decrease in tidal volume, lung compliance, inspiratory duration, and an increase in functional residual capacity and respiratory frequency. We hypothesized that hypoxemia induced small airway constriction and pulmonary time constant inequalities resulting in a frequency dependent fall in lung compliance and tidal volume and retention of lung volume. In seven newborn subhuman primates, responses to acute hypoxemia were measured prior to and after administration of atropine methyl bromide to prevent vagally mediated narrowing of peripheral airways. The increase in frequency and fall in inspiratory duration characteristic of the ventilatory decline during hypoxemia was eliminated by the drug but functional residual capacity and lung compliance were unaffected. Also, the initial rise in V1 was blunted or blocked in all subjects. Bilateral vagotomy caused V1 to fall significantly requiring oxygen supplementation but responses to hypoxemia were still biphasic in nature. These findings suggest that cholinergically mediated mechanisms in the airways do not alter effective lung distensibility related to respiratory rate. Acetylcholine may be important at the peripheral chemosensor since cholinergic blockade eliminated the initial ventilatory increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Animals, Newborn; Atropine Derivatives; Functional Residual Capacity; Hypoxia; Macaca nemestrina; Respiration; Tidal Volume; Vagotomy; Vagus Nerve