Respiratory influence of peripheral chemoreceptor stimulation in maturing rabbits

To evaluate whether the influence of peripheral chemoreceptor (PCR) stimulation is centrally modulated by hypoxia, the respiratory effects of sodium cyanide (NaCN) infusion were compared during room air and 10% O2 inhalation in 18 lightly anesthetized, tracheotomized rabbits of varying postnatal age (1-33 days). During normoxia, noncumulative infusions of NaCN (5-400 micrograms/kg body wt) produced dose-dependent ventilatory (VE) stimulation. Maximal VE stimulation (VEmax) and ventilatory sensitivity to NaCN [i.e., log dose producing 50% of VEmax (log ED50)] did not significantly vary with age, with the average VEmax and log ED50 values amounting to 238% above base line and 1.564 micrograms/kg, respectively. During hypoxia, after initial stimulation (average: 152%), VE progressively decreased and stabilized to 67% above the normoxic base-line level. In contrast to normoxia, subsequent NaCN administration during steady-state hypoxia produced dose-dependent VE depression, occasionally manifested by abrupt apnea. The NaCN effect during hypoxia was significantly related to age (P less than 0.05), as well as to the estimated change in CO2 production during hypoxia (P less than 0.01). Both the respiratory depressant effects of hypoxia alone and in combination with NaCN were abolished after denervation of the peripheral chemoreceptors. These findings demonstrate that while PCR stimulation during normoxia produces ventilatory stimulation, the influence of enhanced PCR input during hypoxia is centrally modulated to produce ventilatory depression.