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 micrograms, 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 less than 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 less than 0.05). This loss of autoregulation was completely reversed by NECA. During severe hypotension, 8-PT altered the CBF redistribution towards the brainstem.(ABSTRACT TRUNCATED AT 250 WORDS)
Laudignon
N
N
Developmental Pharmacology and Perinatal Research Unit, McGill University, Montreal, Canada.
Beharry
K
K
Farri
E
E
Aranda
J V
JV
D000241:Adenosine / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000502:physiology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001783:Blood Flow Velocity; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D007022:Hypotension / Q000503:physiopathology*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000134:cerebrospinal fluid; D007288:Inosine / Q000134:cerebrospinal fluid; D010100:Oxygen / Q000378:metabolism; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology; D013552:Swine; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology
D007042:Hypoxanthines; D011983:Receptors, Purinergic; D019271:Hypoxanthine; D019830:Adenosine-5'-(N-ethylcarboxamide); D007288:Inosine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D010100:Oxygen