THE ROLE OF ADENOSINE IN THE VASCULAR ADAPTATION OF NEONATAL CEREBRAL BLOOD-FLOW DURING HYPOTENSION

This study investigated the potential role of adenosine in cerebral blood flow (CBF) regulation in the neonate during moderate and severe hypotension. Experiments were done in anesthetized, 1- to 3-day-old piglets. Regional CBF (determined by radiolabeled microsphere technique) and cerebral metabolic rate for O2 (CMRO2) were measured (a) during normotension and (b) during a 3-min period of moderate (58 +/- 9 mm Hg) or severe (36 +/- 7 mm Hg) hypotension produced by the inflation of a balloon catheter placed in the aortic root. Measurements of CBF and CMRO2 were performed successively after intracerebroventricular (i.c.v.) injections of vehicle (n = 17), the adenosine receptor blocker 8-phenyltheophylline (8-PT, 10-mu-g, n = 14), and the A2-receptor agonist 5'-N-(ethylcarboxamide)adenosine (NECA, 2 ng, n = 8). After i.c.v. administration of vehicle, none of the parameters studied was significantly altered by moderate hypotension, but severe hypotension decreased the total CBF (mean +/- SD) from 86 +/- 24 to 40 +/- 15 ml min-1 100 g-1 and CMRO2 from 3.2 +/- 0.8 to 1.8 +/- 1.0 ml min-1 100 g-1 (p < 0.05). Administration of 8-PT did not alter these parameters during normotension, but significantly decreased CBF during moderate hypotension compared to postvehicle values (53 +/- 11 versus 81 +/- 12 ml min-1 100 g-1, p < 0.05). This loss of autoregulation was completely reversed by NECA. During severe hypotension. 8-PT altered the CBF redistribution towards the brainstem. Mean normotensive CSF concentrations of adenosine (0.76 +/- 0.26-mu-M) increased during moderate (1.40 +/- 1.78-mu-M) and severe (2.60 +/- 2.56-mu-M, p < 0.05) hypotension. These data suggest that, in the newborn, adenosine is an important mediator of the cerebral adaptive response to hypotension, even within the range of autoregulation.