Characteristic plethysmographic findings in a guinea pig model of COPD.
1. We have examined the reflex changes in breathing evoked in anaesthetized dogs by stimulation of the afferent vagal C fibres that supply the intrapulmonary and lower extrapulmonary airways. We stimulated bronchial (intrapulmonary) C fibres selectively by injecting bradykinin into the right bronchial artery (the chest had been opened briefly for insertion of a bronchial arterial catheter).2. Bronchial arterial injection of bradykinin (0.15-1.5 mug in 3-6 sec) usually caused a brief bout of rapid shallow breathing, which was sometimes preceded by apnoea. Infusion of bradykinin (0.2-2.0 mug min(-1) for 2-12 min) caused prolonged rapid shallow breathing, the breathing frequency (f) increasing by 19-102% and tidal volume (V(T)) decreasing by 13-87%; end-tidal P(CO2) decreased by 2-9 mmHg in several experiments. Rapid shallow breathing was also evoked by administration of bradykinin aerosol through a lower tracheal cannula.3. Cutting the vagus nerves or cooling them to 0 degrees C abolished the prolonged rapid shallow breathing evoked by bradykinin, but intermittent disturbances of breathing could still be elicited in some dogs. These residual effects often consisted of irregular spasmodic inspirations, which were abolished by avulsion of the right upper thoracic sympathetic chain.4. Rapid shallow breathing was accompanied by contraction of airway smooth muscle in an innervated segment of the upper trachea; contraction was abolished by cutting or cooling the vagus nerves.5. Arterial blood pressure often decreased briefly when bradykinin was injected into the bronchial artery; changes in pressure were smaller and less frequent when bradykinin was infused slowly, and pressure was usually unaltered when bradykinin was administered as an aerosol. Rapid shallow breathing occurred whether pressure decreased, increased or was unchanged. A number of other observations indicated that the changes in breathing were independent of the changes in blood pressure. Changes in heart rate were complex and appeared to result from the interplay of several reflexes. Marked cardiac slowing was evoked by bradykinin aerosol.6. Bradykinin injected into a bronchial artery is known to stimulate bronchial (intrapulmonary) C fibres. Results of recording afferent vagal impulses in the present study indicated that bradykinin administered as an aerosol stimulated bronchial C fibres and also C fibres with endings in the lower trachea and extrapulmonary bronchi. Irritant and pulmonary stretch receptors were not stimulated unless aerosols were administered repeatedly and in higher concentration. Hence airway C fibres appeared to be responsible for the reflex effects of bradykinin aerosol.7. Bronchial C fibres are stimulated by substances (bradykinin, prostaglandins and histamine) known to be released by the lungs and airways in a variety of pathophysiological circumstances. Results of this and previous studies are compatible with the hypothesis that stimulation of bronchial C fibres plays a major role in evoking the rapid shallow breathing, bronchoconstriction and increased secretion by airway submucosal glands that are part of the pulmonary defence response.