The Role of Adenosine in the Vascular Adaptation of Neonatal Cerebral Blood Flow during Hypotension

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Abstract
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 μg, 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 μ M) increased during moderate (1.40 ± 1.78 μM) and severe (2.60 ± 2.56 μ 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.