The incidence of asthma is increasing worldwide with a 250% increase in the US over the past 20 years. In 2001 the NIH estimated that 17 million Americans suffer from asthma and 12.1 million from COPD. An increasing number of patients with these diseases require anesthesia and bronchospasm especially during induction and emergence from anesthesia carries significant morbidity. A better understanding of therapies that minimize bronchospasm during anesthesia will make anesthetic care safer for a growing number of patients with asthma and COPD. Intubation of the trachea during induction or the presence of an endotracheal tube during emergence from anesthesia initiates a neurally-mediated irritant reflex in the airway promoting bronchoconstriction. Neural control of airway tone is modulated by both cholinergic nerves traveling within the vagus nerve and by nocioceptive C fibers that send afferent signals to the CMS that modulate cholinergic outflow and locally release tachykinins into the airway wall. In brain, tachykinins release v-amino butyric acid (GABA), the primary neuronal inhibitory neurotransmitter. The cholinergic component of this reflex has been extensively explored in animal models and humans but little is known regarding the contribution of C fibers, released tachykinins or GABA to reflex-induced bronchoconstriction. Propofol is known to allosterically enhance the activity of GABA at GABAA receptors in the brain and is recognized as the intravenous anesthetic induction agent of choice in patients at risk for bronchospasm but its mechanism of airway protection is poorly understood. Elucidating the mechanisms of propofol's protective airway effects may provide novel therapies for bronchoconstriction from many causes. Exciting preliminary data demonstrate that [1] GABA is locally present near airway smooth muscle, [2] airway smooth muscle expresses GABAA receptors, [3] GABAA agonists relax airway smooth muscle and [4] propofol selectively attenuates NK2-mediated airway constriction via GABAA receptors. Based on these preliminary data we hypothesize that airway irritation releases tachykinins which activate NK2 receptors on airway nerves to release GABA which allows for the allosteric potentiation at airway smooth muscle GABAA receptors by propofol to facilitate relaxation.
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