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 less than 1 mg/l) or 8 mg/kg (group 3, n = 7, mean CSF levels less than 3.5 mg/l); and 7 received an intracerebroventricular injection of 10 micrograms 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 less than 0.01). CBF increase secondary to severe hypoxia was attenuated only in group 4 (74 +/- 29%, P less than 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 less than 0.005) to maximal CSF levels of adenosine (r = 0.73), inosine (r = 0.87), and hypoxanthine (r = 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)
Laudignon
N
N
Developmental Pharmacology and Perinatal Research Unit, McGill University, Montreal, Quebec, Canada.
Farri
E
E
Beharry
K
K
Rex
J
J
Aranda
J V
JV
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000134:cerebrospinal fluid / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001158:Arteries; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000134:cerebrospinal fluid; D000860:Hypoxia / Q000503:physiopathology*; D007276:Injections, Intraventricular; D007288:Inosine / Q000134:cerebrospinal fluid; D010100:Oxygen / Q000097:blood; D013552:Swine; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid / Q000494:pharmacology; D014655:Vascular Resistance
D007042:Hypoxanthines; D019271:Hypoxanthine; D007288:Inosine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D010100:Oxygen