Dyspnea, an unpleasant sensation of difficulty in breathing, is a common symptom in patients with cardiopulmonary diseases, but the underlying mechanisms are unclear. Amongst the various neural pathways, unmyelinated vagal C fibers arising from the lungs and airways have been implicated. The long-term objectives are to increase understanding of the mechanisms of dyspnea and specifically the role of pulmonary C fibers. Adenosine is a commonly used therapeutic intravenous drug for treatment of supraventricular tachycardia; it has been frequently reported to cause dyspnea. Recent studies from our laboratory reported the first evidence showing that adenosine stimulates pulmonary C fiber receptors in anesthetized rats. Preliminary human studies from our laboratory indicate that intravenous adenosine causes dyspnea and increase ventilation, and neither affect is associated with bronchoconstriction. Adenosine is known to increase ventilation by stimulating the carotid body chemoreceptors; such reflex stimulation would increase central motor command and could lead to the development of dyspnea. Our hypothesis is that adenosine causes dyspnea by direct activation of pulmonary C fiber, and it is not an indirect effect related to the increase in ventilation.
The specific aims of the proposed study are: 1) to determine the latency and magnitude of dyspneic response, change in airway resistance, and ventilatory response to intravenous injection of adenosine in normal subjects and stable asthmatics; 2) to evaluate the effects of pretreatment with theophylline, and adenosine receptor antagonist, on the intensity of dyspnea and the ventilatory effects of intravenous adenosine; 3) to examine whether directly blocking pulmonary C fibers with inhaled lidocaine abolishes the sensation of dyspnea induced by adenosine in these subjects/patients; 4) to investigate if pretreatment with 100 percent O2, by reducing carotid chemoreceptor sensitivity, alters the dyspnogenic and ventilatory effects of intravenous adenosine. These studies should bring a better understanding of the underlying mechanism of adenosine-induced dyspnea and the role of bronchopulmonary C fibers.
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