Effect of a new hyperosmotic agent, NIK-242 injection, on brain water content, metabolites and cerebral blood flow in cerebral ischemia in the spontaneously hypertensive rat.
We examined the effects of a new hyperosmotic agent (NIK-242inj.) on brain edema, energy metabolites and regional cerebral blood flow (r-CBF) during acute cerebral ischemia. Cerebral ischemia was induced by bilateral common carotid artery ligation (BLCL) using spontaneously hypertensive rats (SHR). The experimental animals were divided into 4 groups, A:20% NIK-242inj., B:20% mannitol, C:10% glycerol in 5% fructose, D:normal saline. All the animals were administered the agent or saline intravenously beginning at 1h after BLCL and continuing for 2h for a total dose of 6.8 ml/kg body weight. Brain water content and metabolites (ATP, lactate, pyruvate) were determined 3h after BLCL. Regional cerebral blood flow (r-CBF) in thalamus was also measured by the hydrogen clearance technique. The brain water content in the NIK-242inj. group was significantly lower than that of saline group. The concentration of brain ATP in the NIK-242inj. group remained higher than those of saline group. Accumulation of lactate in the NIK-242inj. group was less than in the mannitol and saline groups. The lactate/pyruvate ratio of the NIK-242 inj. group was significantly lower than that of the saline and mannitol groups. At 3h after BLCL, the reduction of r-CBF in the NIK-242inj. group was smaller than that of saline group. The present study suggests that NIK-242inj. as well as glycerol could ameliorate brain edema, disruption of brain energy metabolism and reduction of r-CBF in acutely induced cerebral ischemia.
Kashiwagi
F
F
2nd Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Katayama
Y
Y
Shimizu
J
J
Kamiya
T
T
Terashi
A
A
D000818:Animals; D001834:Body Water / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004896:Erythritol / Q000494:pharmacology / Q000627:therapeutic use*; D005990:Glycerol / Q000494:pharmacology; D007267:Injections; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR
D008353:Mannitol; D005990:Glycerol; D004896:Erythritol