Ventilatory effect of an adenosine analogue in unanesthetized rabbits during development

The effect of an adenosine analogue N6-L-(R-phenylisopropyl)adenosine (R-PIA) on respiration was studied in rabbit pups (1-8 days old). Respiration was monitored by a noninvasive barometric method during natural sleep. The adenosine analogue was given by an indwelling intraperitoneal catheter. R-PIA given in a dose of 0.1 mumol/kg (380 micrograms/kg) body wt caused a decrease of the ventilation. The respiratory decrease could be reversed or prevented by pretreatment with theophylline (10 mg/kg). R-PIA caused a considerably more pronounced effect in 1- to 3-day-old animals than in 8-day-old animals. This effect was seen both when the ambient temperature was held at 28 (P less than 0.01) and 32 degrees C (P less than 0.05). Determination of R-PIA receptors in whole brains of rabbit pups of various ages showed that R-PIA bound with higher affinity to membranes from newborn animals (Kd 0.53 nM) than older animals (Kd 0.7-1.26). Since adenosine is released during hypoxia, it may be involved in "hypoxic depression" of respiration in neonates and apnea of prematurity. This might also explain the potent therapeutic effect of the adenosine antagonist theophylline on recurrent apnea in preterm infants.