[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.