Abstract
Evidence has accumulated from previous studies that vagal fibers in the lungs are involved in the genesis of dyspnea. In a series of human studies, based on our previous animal data (J Physiol 1998; 508:109-18; J Appl Physiol 1998; 84:417-24; J Appl Physiol 2003; 95:1315-24) we established that intravenous adenosine has a dyspnogenic effect (J Appl Physiol 2005; 98:180-5; Respir Res 2006; 7:139; Pulm Pharmacol Ther 2008; 21:208-13), strongly implicating a role for vagal C-fibers in the genesis of dyspnea. We have now analyzed the relative effects of blockade of vagal C-fibers by two methods and routes of delivery: by inhibition of the sodium channel and interruption of action potential conduction in the nerve by inhaled local anesthetic (lidocaine), and by blockade by systemic theophylline, a known, nonselective adenosine receptor antagonist. Both techniques significantly (p < 0.05) attenuated the dyspneic response to intravenous adenosine. However, the attenuation was significantly (p < 0.05) greater with pretreatment with systemic theophylline (mean change in response, DeltaAUC -44%) versus pretreatment with inhaled lidocaine (mean change in response, DeltaAUC -11.8%). These differences in the results of airway sensory nerve blockade probably reflect different populations of C fiber receptors and may explain conflicting results of previous studies of dyspnea and airway anesthesia.