Influence of adenosine on cerebral blood flow during hypoxic hypoxia in the newborn piglet

Abstract

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)

Anoxic Injury-Associated Cerebral Hyperperfusion Identified with Arterial Spin-Labeled MR Imaging

“…4,20,[29][30][31][32][33][34][35][36][37] Animal models have shown a loss of cerebral vascular resistance in the postanoxic state resulting in uncontrolled hyperperfusion. [38][39][40][41][42] Cerebral blood volume has been shown to increase with loss of autoregulation secondary to ischemia, but no large studies have demonstrated a similar relationship for CBF. 43 Relative hyperperfusion has been shown in the thalamus, cerebellum, and occipital lobes with O-15 PET imaging in resuscitated patients; however, this method does not quantitate flow.…”

Postnatal development of the pattern of respiratory and cardiovascular response to systemic hypoxia in the piglet: the roles of adenosine.

“…The fact that 8-PT had no effect on the sustained ventilatory response to hypoxia in the 3-week-old piglets is perhaps surprising since the concentration of adenosine in the cerebrospinal fluid of 1-month-old piglets has been shown to rise substantially during hypoxia (Pa,o2: 27 mmHg; Laudignon et al 1991). By this age, the stimulatory effect of the peripheral chemoreceptors upon ventilation can apparently overcome the depressive effect of centrally released adenosine, at least during hypoxia lasting 5 min.…”

Adenosine and Neopterin Levels in Cerebrospinal Fluid of Patients with Neurological Disorders.

“…Brain adenosine levels have been shown to rise in the brain interstitial fluid or cerebrospinal fluid (CSF) soon after the onset of total ischemia and hypoxia (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Adenosine in CSFis thought to be responsible for the cerebral vasodilatation which increases CBF,because a ventriculocisternal perfusion of adenosine causes an increase in CBF (14), and because the instillation of adenosine deaminase or a potent adenosine receptor blocker, 8-phenyltheophylline or theophylline into CSFreduces the hypoxic and hypercapnic dilatation or rat pial arterioles or CBF, respectively (3,15).…”