The effects of centrally administered adenosine on fetal sheep heart rate accelerations.

Abstract

We examined the effect of administering a long-acting adenosine analog, L-2-N6-(phenylisopropyl) adenosine, into the cerebrospinal fluid of the fourth ventricle on fetal sheep heart rate accelerations. Pregnant ewes between 123 and 130 days' gestation were anesthetized, and the fetal head was exteriorized. Catheters were placed in the fourth cerebral ventricle through the foramen magnum and in the brachial artery to record fetal heart rate. Studies were performed in unanesthetized fetuses 4 to 7 days after surgery. Accelerations were defined as a 10 beats/min rise in heart rate for at least 5 seconds. The mean number of accelerations before administration of L-2-N6- (phenylisopropyl) adenosine was 3.9 +/- 0.7 (mean +/- SE) per 10-minute epoch, decreasing to 2.0 +/- 0.7 and 1.4 +/- 0.8 after instillation of 0.2 microgram and 0.5 micrograms of L-2-N6-(phenylisopropyl) adenosine, respectively (p < 0.05). Increasing the L-2-N6-(phenylisopropyl) adenosine dose to 10.0 micrograms resulted in loss of heart rate accelerations. Accelerations were not reduced when theophylline, an adenosine receptor blocker, was given before L-2-N6-(phenylisopropyl) adenosine. Increasing amounts of a centrally administered adenosine analog progressively decreased the number of fetal sheep heart rate accelerations, most probably by suppression of brainstem sympathetic outflow.