Cerebral Blood Flow and Metabolic Rate Early and Late in Prolonged Epileptic Seizures Induced in Rats by Bicuculline

Abstract

Cerebral blood flow (CBF) and cerebral metablic rate for oxygen (CMRO2) have been studied during sustained epileptic seizures induced by bicuculline (1-2 mg/kg, i.v.) in paralysed Wistar rats, artificially ventilated with nitrous oxide/oxygen. CBF was determined by venous outflow collection, and by 133Xe desaturation, using sagittal sinus blood (for cerebral cortical flow) or retroglenoid venous blood (for 'whole brain' flow). The procedure employed ensured that arterial oxygenation remained normal and blood glucose concentration was normal or high throughout the seizure. Arterial hypotension was prevented by the infusion of donor blood. CBF increased concurrently with seizure onset, reaching a maximum nine times higher than control value after 15-60 s. This was due to a marked rise in mean arterial pressure (to greater than 180 torr) and a dramatic fall in cerebrovascular resistance to less than 15 per cent of control). Subsequently, with decreasing blood pressure, CBF slowly diminished, being more than four times higher than control at 20 min, and slightly less than three times higher than control at two hours. The different procedures for measuring CBF gave closely similar results. A threefold increase relative to control CMRO2 (7-6 ml/100 g-1/min-1 for 'whole brain,' and 10-2 ml/100 g-1/min-1 for cerebral cortex) was measured after 1-20 min of seizure activity (utilizing either the venous outflow or the 133Xe desaturation procedure for CBF determination). After two hours of seizure activity CMR02 was still more than twice as high as the control. This high metabolic rate during sustained seizure activity will increase the susceptibility of the brain to 'ischaemic' damage during prolonged seizures in man in which an additional metabolic stress may be imposed by cerebral hypoxia, arterial hypotension, hyperpyrexia or hypoglycaemia.

Local Cerebral Blood Flow with Fentanyl-Induced Seizures

“…For illustrative purposes, ictal suppression, the LCVR decrease remained sig nificant in the majority of the brain structures (16 of 29 structures). There were no differences in the LCVR changes between the spike, seizure, and suppression states (Table 4) (Plum et aI., 1968;Plum and Duffy, 1975;Meldrum and Nilsson, 1976). However, they expand our un Another factor requires consideration in ex plaining the differences between these two studies.…”

Importance of Vascular Responses in Determining Cortical Oxygenation during Recurrent Paroxysmal Events of Varying Duration and Frequency of Repetition

“…(1975). In addition, it has been reported that CMROz was only moderately decreased despite a large decrease in CBF late in recurrent seizures (Meldrum and Nilsson, 1976;Chapman et aI., 1977;Blennow et aI., 1979). Inter pretation of CMROz data must take into account that such measurements indicate steady-state met abolic activity of relatively large tissue volumes.…”

“…In contrast to expectations, sys temic and cerebral vascular responses and associated in creases in cerebral oxygenation were better maintained during long-duration ictal episodes than during short-duLocal brain O2 supply is regulated in proportion to the intensity of local functional activity and met abolic demand (Kuschinsky and Wahl, 1978). The question remains, however, whether this relation ship is maintained during recurrent seizures (Plum et aI., 1974;Meldrum and Nilsson, 1976; Blennow et aI., 1978; Kreisman et aI., 1983a). In previous studies, we demonstrated that there is a transition from oxygen sufficiency to insufficiency in cerebral cortex during recurrent seizures (Kreisman et aI., 1981b(Kreisman et aI., , 1983a.…”

“…Inadequate systemic blood pressure during seizures had been shown previously to decrease cerebral POz, reverse responses of respiratory chain members from oxidation to reduction (Plum et aI., 1968;Vern et aI., 1976;Hempel et aI., 1980;Kreisman et aI., 1981b), and cause cerebral metabolic derangements characteristic of ischemia (Astrup et aI., 1979;Vern et aI., 1979). It has been suggested that any de crease in CBF below normal in recurrent seizures during which the cerebral metabolic rate for oxygen (CMROz) increases two-to threefold likely should induce cerebral ischemia, since low CBF levels would not supply sufficient Oz to meet such an in creased level of demand (Meldrum and Nilsson, 1976;Astrup et aI., 1979;Heiss et aI., 1979).…”

“…The question remains, however, whether this relation ship is maintained during recurrent seizures (Plum et aI., 1974;Meldrum and Nilsson, 1976;Blennow et aI., 1978;Kreisman et aI., 1983a). In previous studies, we demonstrated that there is a transition from oxygen sufficiency to insufficiency in cerebral cortex during recurrent seizures (Kreisman et aI., 1981b(Kreisman et aI., , 1983a.…”