INFLUENCE OF ADENOSINE ON CEREBRAL BLOOD-FLOW DURING HYPOXIC HYPOXIA IN THE NEWBORN PIGLET

This study investigated the role of adenosine in the regulation of neonatal cerebral blood flow (CBF) during moderate (arterial PO2 = 47 ± 9 Torr) and severe (arterial PO2 = 25 ± 4 Torr) hypoxia. Twenty-eight anesthetized and ventilated newborn piglets were assigned to four groups: 8 were injected intravenously with the vehicle (controls, group 1); 13 received an intravenous injection of 8-phenyltheophylline (8-PT), a potent adenosine receptor blocker, either 4 mg/kg (group 2, n = 6, mean cerebrospinal fluid (CSF) levels < 1 mg/l) or 8 mg/kg (group 3, n = 7, mean CSF levels < 3.5 mg/l); and 7 received an intracerebroventricular injection of 10 μg 8-PT (group 4). During normoxia, CBF was not altered by vehicle or 8-PT injections. In group 1, 10 min of moderate and severe hypoxia increased total CBF by 112 ± 36 and 176 ± 28% (SE), respectively. Compared with controls, the cerebral hyperemia during moderate hypoxia was not altered in group 2, attenuated in group 3 (to 53 ± 13%, P = NS), and completely blocked in group 4 (P < 0.01). CBF increase secondary to severe hypoxia was attenuated only in group 4 (74 ± 29%, P < 0.05). CSF concentrations of adenosine and adenosine metabolites measured by high-performance liquid chromatography increased during hypoxia. Arterial O2 content was inversely correlated (P < 0.005) to maximal CSF levels of adenosine (r = 0.73), inosine (r = 0.87), and hypoxanthine (r = 0.80). In the absence of adenosine-receptor blockade, CBF values were correlated (P < 0.005) to CSF concentrations of inosine (r = 0.55) and hypoxanthine (r = 0.50). The data strongly suggest that, during hypoxic hypoxia, adenosine has an important role in the regulation of cerebral hyperemia of the newborn.