Long-term recurrent hypoxia in developing rat attenuates respiratory responses to subsequent acute hypoxia

Whereas definitive treatment of pediatric conditions associated with hypoxemia reverses many pathologic symptoms, some physiologic dysfunctions appear to persist. These abnormalities are attributed to long-lasting central effects of prior hypoxia. To investigate such effects in an animal model, male rats were exposed to FiO2 = 0.12 continuously for 7 h daily from postnatal day (p) 17 (representing early childhood) through p33 (representing adolescence), defined as recurrent hypoxia. Respiratory responses during and following 20 min FiO2 = 0.12 were measured on p35 and p47. To control for early weaning on p15 (normal weaning = p21), male rats were weaned on either p15 or p21, raised in normoxia, and also tested for respiratory responsiveness to acute hypoxia. To assess sex differences, female rats were assigned to similar groups and protocols. Minute ventilation, respiratory frequency, tidal volume, and respiratory drive were measured in unsedated animals using whole-body plethysmography. After recurrent hypoxia, male rats displayed an attenuation of ventilation, frequency, and drive during hypoxia, and of all functions after hypoxia on both p35 and p47. There were no differences between test days during hypoxia, and greater attenuation of tidal volume and respiratory drive on p47 during recovery from hypoxia. Respiratory responses displayed no effect of sex on p35, and occasional effects of early weaning on p35 and p47. Thus, recurrent hypoxia produces long-lasting attenuation in respiratory responsiveness to subsequent acute hypoxia. Such long-lasting attenuation, if present in humans, may diminish the protection of children with a history of recurrent hypoxemia against future hypoxic events.