A. M. Roberts

Stimulation of pulmonary vagal afferent C-fibers by lung edema in dogs.

In anesthetized, open-chest dogs we examined the effect of pulmonary edema on the firing frequency of afferent vagal fibers arising from the lung. We recorded impulses from slips of the cervical vagus nerves and infused isotonic Krebs-Henseleit solution (20% of body weight) intravenously to increase net filtration pressure in the lung microvasculature. Measurement of extravascular lung water (6.0 ± 0.4 g/g dry lung), and morphological examination of lung tissue (revealing various degrees of perivascular and peribronchial cuffing) confirmed that edema was present. At the end of the infusion when the lungs were congested (lung microvascular pressure, 37 cm water) and edematous, the impulse frequency of pulmonary and bronchial C-fibers and rapidly adapting receptors had increased 5–6 times. The only significant change in slowly adapting receptor activity was an increase during deflation. When lung water was still elevated but lung microvascular pressure had been restored to control by withdrawal of blood, impulse activity of rapidly and slowly adapting receptors reverted to or below control. Pulmonary C-fiber activity, although less than during congestion, remained significantly above control, several C-fibers being stimulated by interstitial edema in the absence of alveolar edema. Bronchial C-fibers were stimulated in severely edematous lung showing pronounced peribronchial cuffing and alveolar edema, but were not stimulated in milder grades of edema. Our results support the hypothesis (Paintal, 1969) that pulmonary C-fibers (J-receptors) are stimulated by an increase in interstitial pressure secondary to edema.

Rapid shallow breathing evoked by selective stimulation of airway C fibres in dogs

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).

Attenuation of pulmonary afferent input by vagal cooling in dogs

In open chest, artificially ventilated, anesthetized dogs, we examined the effect of vagal cooling on the pulmonary afferent input evoked by hyperinflating the lungs to 3 VT, recording the activity of slowly adapting pulmonary stretch receptors (PSRs), rapidly adapting receptors (RARs) and pulmonary C fibers rostral to the cooling platform. At 15 degrees C and below, input in all three types of fiber was significantly reduced, attenuation being least marked in C fibers. Between 12 degrees C and 7 degrees C, attenuation of RAR input was significantly less than that of PSRs. At 7 degrees C, virtually none of the hyperinflation-evoked increase in PSR activity and only 10% of that in RARs passed the cooling platform--indeed RAR input was less than during normal ventilation at 37 degrees C; by contrast, 40% of the hyperinflation-evoked increase in C fiber activity was still transmitted. Cooling had similar effects on C fiber input evoked by capsaicin. If reflexes are attenuated in proportion to the attenuation of afferent input, our results suggest that a hyperinflation-evoked reflex that survives vagal cooling below 6 degrees C is almost certainly triggered by C fibers.

Vagal chemoreflex coronary vasodilation evoked by stimulating pulmonary C-fibers in dogs.

We performed experiments on anesthetized, open-chest dogs to determine whether the pulmonary chemoreflex (bradycardia and systemic hypotension) evoked by stimulating pulmonary C-fibers also involves reflex changes in coronary vascular resistance. We perfused the circumflex coronary artery at constant pressure (usually 100 mm Hg) and recorded mean circumflex blood flow. Stimulation of pulmonary C-fibers by right atrial injection of capsaicin (10 micrograms/kg) decreased arterial blood pressure and heart rate and increased circumflex blood flow by 32-109% (P less than 0.001). Circumflex blood flow also increased, by 26-100% (P less than 0.001), when heart rate was kept constant by pacing. Coronary vasodilation was not secondary to the reflex decrease in arterial blood pressure. Injecting capsaicin (10 micrograms/kg) into the left atrium did not increase circumflex blood flow. Reflex coronary vasodilation could still be evoked when myelinated nerve fibers were blocked selectively by cooling the cervical vagus nerves to 7-8 degrees C but was abolished by cooling to 0 degrees C, by cutting the pulmonary vagal branches, or by giving atropine. Reducing coronary perfusion pressure shifted the stimulus (dose of capsaicin)-response (increase in coronary blood flow) curve to the right, but, even at low perfusion pressures, significant reflex vasodilation still occurred. Regional (transmural) distribution of myocardial blood flow was measured by the microsphere technique at various perfusion pressures. The endocardial:epicardial blood flow ratio decreased significantly as perfusion pressure was reduced, but was not altered by right atrial injection of capsaicin at any perfusion pressure. Our results indicate that stimulation of pulmonary C-fibers triggers reflex cholinergic vasodilation in all layers of the myocardium.

Reciprocal action of pulmonary vagal afferents on tracheal smooth muscle tension in dogs.

Tracheal smooth muscle usually relaxes when the lungs are transiently inflated, an effect attributed to inhibitory input from pulmonary stretch receptors (PSRs). Relaxation is often followed by contraction, however, and occasionally contraction is the sole response. We attempted to identify the afferents responsible for this reflex contraction. In anesthetized, artificially ventilated dogs with open chest we recorded transverse tension in an upper tracheal segment innervated only by the superior laryngeal nerves and periodically hyperinflated the lungs as the cervical vagus nerves were cooled. Hyperinflation usually evoked tracheal relaxation when vagal temperature was 37 degrees C, but contraction became more frequent as temperature decreased and was the sole response below 8 degrees C. We hypothesise that above 6 degrees C contraction was triggered by rapidly adapting receptors and lung C fibers, whereas below 6 degrees C only C fibers were involved. Contraction, which appeared to represent the bronchomotor counterpart of Heads paradoxical reflex, was abolished below 2 degrees C. Cooling alone without periodic hyperinflation increased baseline tracheal tension to a maximum at 7-8 degrees C; further cooling often decreased tension, sometimes to control levels. Cutting the pulmonary vagal branches abolished these effects. Our results indicate that PSRs and C fibers act reciprocally, one causing bronchodilation, the other bronchoconstriction, and that background activity in C fibers may contribute to bronchomotor tone, an effect unmasked by selectively blocking A fibers.