THE EFFECT OF CENTRALLY ADMINISTERED ADENOSINE ON FETAL BREATHING MOVEMENTS

The central effects of the adenosine analogue L-2-N6-(phenylisopropyl) adenosine (L-PIA) on breathing movements was determined by making injections into the fourth ventricle in unanesthetized fetal sheep. Administration of 0.5-mu-g L-PIA reduced the percent time during which fetal breathing occurred from 48.0 +/- 5.2 (SEM) to 19.5 +/- 6.1. Inspiratory slope was reduced to 62 +/- 5.5 and to 43 +/- 5.7 percent of the control values when 0.2 and 0.5-mu-g L-PIA were given respectively. The effects of L-PIA on the percent time fetal breathing movements occurred and on inspiratory slope were prevented by the prior systemic administration of theophylline (plasma concentrations approximately 15-mu-g/ml). When the vehicle for L-PIA, dimethyl sulfoxide in Ringer solution was given into the fourth ventricle or when 0.5-mu-g L-PIA was given systemically, there was no effect on fetal breathing. None of these protocols resulted in a change in sagittal sinus blood pH, P(o2) or, P(co2). These data indicate adenosine acts at the brain stem to depress fetal respiratory drive.