|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1998 : ¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1997 : ¥1,300,000 (Direct Cost : ¥1,300,000)
We hypothesized that neonatal deprivation of peripheral chemoreceptor inputs by perinatal hyperoxia (hyperoxic denervation) irreversibly impairs the hypoxic ventilatory response in adults rats. To test the hypothesis, the pregnant rats were put into chambers flushed continuously with 50-60 % oxygen or air (hyperoxic group, HOG ; normoxic group, CONT). Litters (n=10 for HOG and n=8 for CONT) were born two days after starting hyperoxic exposure, which then continued for 4 weeks. Eight to twelve weeks after hyperoxic exposure, animals were anesthetized with urethane (1 .2g/kg, i.p.). The arterial blood gas (Paco_2 and Pao_2), ventilatory parameters (VT, tidal volume ; f, respiratory frequency ; VE, minutes ventilation) and the ventilatory response to hypoxia (F_<IO2> = 0.40, 0.21, 0.15, 0.10) were measured. During breathing air, there were no significant differences in ventilatory parameters and Paco_2 or Pao_2 between both groups. However, the ventilatory response to hypoxia was attenuated by 45% in HOG as compared to CONT.
Our results indicated that the hyperoxic denervation by perinatal hyperoxia irreversibly impaired the hypoxic ventilatory responsiveness without any changes in the baseline ventilatory parameters and arterial blood gas values. Neonatal deprivation of peripheral chemoreceptor inputs by perinatal hyperoxia induced the developmental plasticity of the neuronal circuit involved in the hypoxic ventilatory response, and hence attenuated the ventilatory responsiveness to hypoxia.