1660 MATURATIONAL RESPIRATORY RESPONSE TO ENDOGENOUS OPIATES IN NEWBORN RABBITS

Abstract

Significant changes in respiratory control occur in the human neonate during the early post-natal period. These changes may be related to the action of endorphins, which have been isolated from amniotic fluid and cord blood, and are known to affect respiration. To determine the maturational effects of these agents on respiration, we measured ventilation (V_E), tidal volume (V_T) and respiratory frequency (f) in 18 rabbit pups (age range: 1 to 19 days) before and after systemic administration of D-Ala²,D-Leu⁵ enkephalin (ENK). Tracheostomy and carotid artery catheterization were performed under light ether anesthesia. After anesthetic recovery the pups were placed in a body plethysmograph. Saline infusion had no effect. Twenty minutes after infusion of 0.5 ug/g ENK, however, V_E was significantly reduced in all pups, ranging from 25 to 80% below control. The V_E changes were secondary to decreases in f, although V_T increased (+15 to +65%) due to prolongation of inspiratory duration. The degree of V_E depression varied inversely with age, being most marked in pups < 4 days old. Indeed, in 4 of 7 pups < 4 days old, ENK produced periodic breathing with apnea. All effects of ENK were abruptly reversed with infusion of naloxone (0.8μg/g), an opiate antagonist. These data provide evidence that: a) opiate-like peptides depress ventilation but their effect diminishes with age; b) early in post-natal life these agents may cause periodic breathing with apnea.

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