CEREBROVASCULAR RESPONSE DURING AND FOLLOWING SEVERE INSULIN-INDUCED HYPOGLYCEMIA - CO2-SENSITIVITY, AUTO-REGULATION, AND INFLUENCE OF PROSTAGLANDIN SYNTHESIS INHIBITION

Mechanisms governing cerebrovascular responses during severe hypoglycemia, and in the posthypoglycemic recovery period were studied. Lightly anesthetized (70% N2O) and artificially ventilated rats were injected with insulin so as to abolish EEG activity for 15 or 30 min (coma). In separate animals, recovery was induced by glucose administration. Previous experiments showed that in normo- or moderately hypertensive animals hypoglycemic coma is accompanied by a relatively marked increase in cerebral blood flow (CBF), and that a delayed hypoperfusion develops in the recovery period. O2 supply is in excess of the demands during coma, and falls below control during recovery. During hypoglycemic coma, the CO2 response of the circulation was retained but autoregulation was lost. In the recovery period, both CO2 response and autoregulation were lost. Pretreatment with indomethacin was introduced to evaluate the possible influence of fatty acid cyclooxygenase products on the pattern of CBF changes. Measurements of local CBF (l-CBF) showed that, in the majority of structures analyzed, indomethacin failed to modulate the changes in CBF. Alterations in cerebrovascular tone and loss of autoregulation induce flow changes that may influence substrate and O2 availability during hypoglycemia. The pronounced decrease in CBF and the loss of autoregulation and CO2-response in the post-hypoglycemic period may influence functional, metabolic and morphological recovery. The l-CBF findings indicate that neither the increase in CBB during hypoglycemia nor the reduction in flow in the posthypoglycemic period are mediated by mechanisms related to prostaglandin metabolism.