Vulnerability of neonatal respiratory neural control to sustained hypoxia during a uniquely sensitive window of development

摘要

The first postnatal weeks represent a period of development in the rat during which the respiratory neural control system may be vulnerable to aberrant environmental stressors. In the present study, we investigated whether sustained hypoxia (SH; 11% O_2) exposure starting at different postnatal ages differentially modifies the acute hypoxic (HVR) and hypercapnic ventilatory response (HCVR). Three different groups of rat pups were exposed to 5 days of SH, starting at either postnatal age 1 (SH_(1-5)), 11 (SH_(11-15)), or 21 (SH21-25) days. Whole body plethysmography was used to assess the HVR and HCVR the day after SH exposure ended. The primary results indicated that 1) the HVR and HCVR of SH_(11-15) rats were absent or attenuated (respectively) compared with age-matched rats raised in normoxia; 2) there was a profoundly high (-84% of pups) incidence of unexplained mortality in the SH_(11-15) rats; and 3) these phenomena were unique to the SH_(11-15) group with no comparable effect of the SH exposure on the HVR, HCVR, or mortality in the younger (SH_(1-5)) or older (SH_(21-25)) rats. These results share several commonalities with the risk factors thought to underlie the etiology of sudden infant death syndrome, including 1) a vulnerable neonate; 2) a critical period of development; and 3) an environmental stressor.