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388 RESPIRATORY EFFECTS OF AN ADENOSINE ANALOGUE AND THEOPHYLLINE IN NON ANAESTHETIZED RABBIT PUPS

Recent studies have indicated that the respiratory stimulatory effect of theophylline in neonates is rather due to antagonism of endogenously released adenosine than by inhibition of phosphodiesterase. This was tested in non-anaesthetized rabbit pups. A adenosine analogue L-N6-phenyl-isopropyl-adenosine (PIA) was injected i.p. in 17 pups. Respiratory volumes were recorded with the barometric method during natural sleep. Ventilatory volumes decreased 65.2 ± 6.0% (SD, n=4) 15 min. after PIA was given to the one day old pups, while the effect was less pronounced in the 3 and 8 days old pups (-43.4 + 5.8%, n=4; -31.0 ± 13.5%, n=3). A linear dose-dependent respiratory depression was found in the concentration range from 0.01-1.0 umol/kg. The respiratory depressive effect could be completely blocked with theophylline pretreatment (10 mg/kg). We found a higher affinity for PIA in the brains from the youngest pups possibly explaining their higher susceptibility. PIA was also found to decrease body temperature, oxygen consumption and cause sedation of the animal. All these effects were reversed with theophylline. These results indicate that adenosine which is released by hypoxia, might be one factor causing respiratory depression--effects which can be antagonized by theophylline.