[Effect of CV-4151 on the cerebral hypoperfusion and production of thromboxane A2 following complete cerebral ischemia-reperfusion in dogs].
The effects of CV-4151 on post-ischemic brain hypoperfusion and thromboxane (Tx)A2 production in a canine model of total global brain ischemia were studied. Complete cerebral ischemia for 5 min was produced in adult mongrel dogs by temporary ligation of the venae cavae and aorta. In the non-treated group, cerebral blood flow (CBF) increased during the first 20 to 30 min post-ischemia followed by a gradual decline and then stayed below preischemic level; CBF at 2 hr after the reperfusion was significantly reduced to ca 77% of the pre-ischemic level. Water content in the cerebral cortex at 2 hr after the reperfusion in the non-treated group was 78.15 +/- 0.21%, higher than the content in the control group, 76.70 +/- 0.07%. The concentration of TxB2 in the sagittal sinus was significantly increased at 30 min post ischemia. CV-4151 (1.0 mg/kg, i.v.) almost completely inhibited the post-ischemic hypoperfusion, significantly inhibited the increase in water content and almost completely inhibited the production of TxB2 in the post-ischemic period and increased the production of 6-keto PGF1 alpha. OKY-046 (10 mg/kg, i.v.) had no significant effects on both post-ischemic hypoperfusion and increase in water content in the cerebral cortex. We conclude that CV-4151 ameliorates post-ischemic cerebral hypoperfusion and that this improvement is associated with decreased sagittal sinus levels of TxB2.
Kito
G
G
Pharmaceutical Research Laboratories II, Takeda Chemical Industries Ltd., Osaka, Japan.
Tanabe
M
M
Terashita
Z
Z
D000818:Animals; D001834:Body Water / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D005229:Fatty Acids, Monounsaturated; D011725:Pyridines; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; C045446:isbogrel