Abstract
Effects of Y-9179 and pentobarbital (PBT) on CBF, CMRO2, SAP and EEG were studied comparatively utilizing Michenfelder's venous outflow model in dogs.
The venous outflow from the superior saggital sinus, the systemic arterial pressure and the intracranial pressure were continuously recorded on a polygraph before and during two hour's continuous intravenous infusion of these agents in the awake condition. A total of 18 dogs was divided equally into three groups. The accumulated doses during the 120 min. period for the Y-9179 and PBT groups were 4mg/kg and 40mg/kg respectively. The control group received the same amount of vehicle as the above groups. CMRO2 was calculated as the product of CBF and AVDO2. The oxygen contents of blood obtained from the femoral artery and the superior saggital sinus were measured by a Lex-O2-con.
Remarkable reduction of CBF was seen with both drugs, which reached about fifty percent of that of the controls. In contrast to the pronounced increase of CVR with PBT, Y-9179 exerted essentially no effects on the CVR. The depressant action on CMRO2 by Y-9179 had already reached a plateau after 45 min, which was only about 80% of the control value. Thereafter, no additional reduction of CMRO2 was seen in spite of continuous administration of Y-9179. There were no remarkable changes in EEG. On the other hand, PBT showed marked depressant action on CMRO2, which reached about fifty percent of the control value. EEG activity was abolished at this point.
These experimental data suggest that Y-9179 has a lower depressant effect on the central nervous system than PBT. Therefore, it is speculated that the protective action of Y-9179 and PBT may not be based only on the reduction of CMRO2. Further investigations on the mechanism of cerebral protection by these drugs, concentrated on other possible actions such as their effects on CBF, are considered mandatory.
