Interrelationships among airway CO2, airway pressure, and breathing frequency.

The breathing frequency response to changes in airway CO2 of a vascularly isolated lobe of the canine lung has previously been shown to be primarily dependent on CO2-mediated changes in airway pressure. This study was carried out to determine what contribution changes in airway pressure make in the whole lung airway CO2-mediated breathing frequency response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. Diaphragm electromyogram (EMG) was used to monitor respiratory center output and to trigger ventilation of the lungs. Isoproterenol administered to the lungs prevented hypocapnic airway constriction but only partially blocked the decrease in breathing frequency, suggesting that in the whole lung preparation, airway CO2 in part alters breathing frequency through a direct effect on pulmonary receptors. At constant positive end-expired pressures (1-6 Torr), 0% airway CO2 produced greater increases in expiratory time than 10% CO2. Thus airway CO2 can affect breathing frequency in the absence of CO2-related changes in airway pressure at pressures that would produce lung volumes similar to those observed at end expiration in the intact animal. An argument is presented that the receptors directly affected by CO2 are probably not located in the airways constricted by hypocapnia.

Location of lung receptors mediating the breathing frequency response to pulmonary CO2.

Pulmonary stretch receptors are thought to mediate the breathing frequency (bf) response to changes in pulmonary CO2. However, the location and distribution of these receptors is disputed. The purpose of this study was to determine what contribution the extrapulmonary receptors make in the pulmonary CO2 bf response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. The diaphragm electromyogram was used to monitor respiratory center output and to trigger a ventilator. Exposure of an upper airway segment to CO2 or positive end-expired pressure failed to produce changes in the bf. Denervation of the upper airway down to but not including the hilum caused similar insignificant changes in the CO2 bf response. Lungs collapsed by suction showed minimal Hering-Breuer inhibition when compared with inflated lungs. Bronchial arterial perfusion with hypocapnic followed by hypercapnic blood failed to produce changes in the bf while similar perfusion of the pulmonary arterial system resulted in significant increases in bf. It appears that the receptors mainly responsible for the pulmonary CO2 response are located in the more peripheral regions of the lung.

Effect of verapamil on pulmonary reflexes in the vascularly isolated canine lung: physiology.

Breathing frequency (BF) may be affected by changes in the percent inspired CO2 administered to vascularly isolated lungs. Pulmonary CO2 probably affects BF, in part, through a secondary effect of CO2 on airway smooth muscle. To further determine the role of pulmonary mechanics in the pulmonary CO2-mediated BF response, Verapamil, a Ca++ blocking agent which blocks hypocapnic airway constriction, was administered to the vascularly isolated lungs of the dog. Verapamil blocked the hypocapnic airway constriction which occurred when pulmonary CO2 was reduced; however, the decrease in BF was not only blocked but in some animals there was an increase in BF. Also, the decrease in BF produced by hyperinflation of the lungs (Hering-Breuer reflex) was either blocked or an increase in BF occurred after administration of Verapamil.

Breathing frequency responses to pulmonary CO2 in an isolated lobe of the canine lung.

Recent studies have indicated that the breathing frequency responses to inspired CO2 in part result from changes in pulmonary stretch receptor activity. Pulmonary CO2 may alter frequency by direct inhibition of stretch receptor discharge, or secondarily, by changes in airway mechanics. The vascularly isolated left lower lobe (LLL) of the canine lung was used to determine the effect of hypocapnic airway constriction on the pulmonary CO2 reflex. The upper and middle lobes of the left lung were removed and the right vagus nerve sectioned. Blood was recirculated through the LLL. Diaphragm electromyogram was used as an index of respiratory center activity and to trigger ventilation of the left lower lobe. Lobar hypocapnia increased peak airway pressure and reduced respiratory rate. However, infusion of isoproterenol or the use of a mechanical overflow system to block the airway pressure response prevented the frequency changes associated with CO2. Although both the direct and mechanical effects of CO2 on stretch receptors may contribute to the reflex, in the LLL preparation the mechanical effects predominate.