Mechanisms of cerebral protection by pentobarbital and nizofenone correlated with the course of local cerebral blood flow changes.

Abstract

SUMMARY The effects of delayed administration of pentobarbital and a novel imidazole derivative (Nizofenone or Y-9179) on the infarction size following the regional cerebral ischemia were studied using the permanent middle cerebral artery (MCA) occlusion model in cats. The courses of local cerebral blood flow (€CBF) before and after drug administration were also studied using the hydrogen clearance method. The extent of infarction one week after MCA occlusion was significantly smaller in the drug-treated groups than in the control group. Regarding the time-course of (,CBF, there was no significant differences between the control and the Y-9179 groups. On the other hand, pentobarbital administration caused a significant €CBF increase in low-flow areas where the £CBF following MCA occlusion was below 40 ml/lOOg/min. In spite of this flow increase, the corresponding cortical areas underwent infarction. Histological examination of the state of vasogenic edema revealed that the perivascular exudation of plasma fluid in the infarcted area was definitely less in the Y-9179 treated group than in the other groups. Results indicate that redistribution of €CBF may not be involved in the mechanism of cerebral protection by pentobarbital or Y-9179.Stroke, Vol 13, No 6, 1982 IT WAS PREVIOUSLY REPORTED that pentobarbital (PBT) and a novel imidazole derivative (Y-9179 or Nizofenone*) reduced the size of infarction in the brain after permanent middle cerebral artery (MCA) occlusion in cats.1 The protective action of Y-9179 against hypoxia and ischemia had already been demonstrated with various models using rats and mice.2 In addition, Y-9179 has few side effects such as anesthetic or cardio-pulmonary depressant action. Although the mechanism of action of Y-9179 has not been fully elucidated, its moderate depressant action on the cerebral metabolic rate may be involved in its cerebral protective action.3 However, this effect is not so potent as with PBT,4 and the role of the decreased cerebral metabolic rate in the mechanism of cerebral protection is controversial. 5,6 In animal experiments it was shown that a barbiturate (methohexital) altered cerebral blood flow (CBF) so that local CBF (€CBF) in the severely ischemic area was increased and that in the unaffected area was decreased (inverse steal).7 Since such a hemodynamic effect might also be relevant to the action of Y-9179, we undertook the present experiments to evaluate i) effect of delayed administration of PBT or Y-9179 on €CBF as measured by the hydrogen clearance method and ii) overall effects of these drugs in terms of histological changes one week after the ischemic insult, using a permanent MCA occlusion model in cats. 8 -9 Materials and Methods Twenty-four adults cats of both sexes weighing 2.0-*From the Department of Neurosurgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan.tAnd from Research Laboratories, Yoshitomi Pharmaceutical Industries, Fukuoka, Japan.Correspondence to: Chikayuki Ochiai, M.D., Department of Neurosurgery, University of Tokyo ...

Reversible Focal Ischemia in the Rat: Effects of Halothane, Isoflurane, and Methohexital Anesthesia

“…Favorable re distribution of CBF by barbiturates administered during focal ischemia has been reported (Branston J Cereb Blood Flow Me/ab, Vol. 11, No.5, 1991No.5, et al, 1979Feustel et al, 198 1;Ochiai et al, 1982). Because isoflurane decreases cerebrovascular re sistance (Cucchiara et al, 1974), it might reduce blood flow through high-resistance circuits by va sodilating normal vasculature, i.e., by causing a steal phenomenon.…”

Biphasic Liberation of Arachidonic and Stearic Acids During Cerebral Ischemia

“…In the present study, the time course for this FFA accumulation during ischemia was investigated in detail in comparison with the time course for brain ATP depletion. In addition, the effect of a cerebroprotective agent, nizofenone (Yasuda et al, 1978(Yasuda et al, , 1979(Yasuda et al, , 1981Tamura et al, 1979;Ochiai et al, 1982;Saito et al, 1983), on the ischemia-induced FFA liberation and ATP depletion was also examined. The results obtained indicate that a rapid and specific 20:4 liberation occurs only during an early period of ischemia in which brain ATP is still available.…”

Prostaglandin profiles in relation to local circulatory changes following focal cerebral ischemia in cats.

“…10 The electrodes were made of 25 -/im platinum-iridium wires insulated except for the terminal 0.5 mm. Control 1CBF was measured at least twice before MCA occlusion.…”