ADENOSINE AND CEREBROVASCULAR HYPEREMIA DURING INSULIN-INDUCED HYPOGLYCEMIA IN NEWBORN PIGLET

The present study tested the hypothesis that adenosine is involved in mediating the hyperemic response of the newborn brain to hypoglycemia. By use of the cranial window and microdialysis-H-2 clearance methodol ogies, changes in the diameter of pial arterioles (25-50 mum), extrace llular adenosine concentrations ([ADO]), and local cerebral blood flow (CBF) were examined in isoflurane-anesthetized piglets subjected to i nsulin-induced hypoglycemia. Blood glucose concentrations ranged from 10 to 18 mg/dl after insulin administration (25 IU/kg iv). Local CBF i n the frontal cortex increased 36 +/- 12% (P = 0.014) at 30 min of hyp oglycemia (group 1, n = 12; control = 43 +/- 3 ml.min-1.100 g-1). The mean increase in dialysate [ADO] sampled concurrently from the same co rtical area was 59 +/- 29% (P = 0.011; control = 0.11 +/- 0.02 muM). A t 30 min of hypoglycemia, pial diameters increased 55 +/- 10% (P = 0.0 01; group 2, n = 9). The [ADO] in cranial window cerebrospinal fluid ( CSF) increased 217 +/- 71% (P = 0.04) in response to hypoglycemia (gro up 3, n = 8; control = 0.016 +/- 0.006 muM). Local administration of a n adenosine antagonist, 10 muM 8-sulfophenyltheophylline, to the cereb ral cortex before hypoglycemia caused a 38% reduction (P = 0.011) in t he pial arteriolar response at 30 min of hypoglycemia (group 4, n = 9) . Similarly, local superfusion of CSF with 3.7 mM glucose attenuated t he hypoglycemia-induced pial dilation 33% (P = 0.039; group 5, n = 9). Perfusion of microdialysis probes with 3.7 mM glucose in the CSF abol ished the hypoglycemia-induced increase in dialysate [ADO] (group 1). Pial arteriolar diameters did not change when normoglycemic blood gluc ose levels were maintained by intravenous glucose after insulin admini stration (group 6, n = 6). These findings in newborn piglets indicate that hypoglycemia promotes increases in cerebral extracellular [ADO], which contribute to the observed pial dilation and parenchymal hyperem ia.