Kito G, Tanabe M, Terashita Z
Pharmaceutical Research Laboratories II, Takeda Chemical Industries Ltd., Osaka, Japan.
Nihon Yakurigaku Zasshi. 1993 Dec;102(6):413-20. doi: 10.1254/fpj.102.413.
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.
研究了CV - 4151对全脑缺血犬模型缺血后脑灌注不足及血栓素（Tx）A2生成的影响。通过临时结扎成年杂种犬的腔静脉和主动脉造成5分钟的全脑缺血。在未治疗组中，缺血后最初20至30分钟脑血流量（CBF）增加，随后逐渐下降，然后维持在缺血前水平以下；再灌注后2小时的CBF显著降低至缺血前水平的约77%。未治疗组再灌注后2小时大脑皮质的含水量为78.15±0.21%，高于对照组的76.70±0.07%。缺血后30分钟矢状窦中TxB2的浓度显著升高。CV - 4151（1.0毫克/千克，静脉注射）几乎完全抑制了缺血后脑灌注不足，显著抑制了含水量的增加，几乎完全抑制了缺血后TxB2的生成，并增加了6 - 酮 - PGF1α的生成。OKY - 046（10毫克/千克，静脉注射）对缺血后脑灌注不足和大脑皮质含水量增加均无显著影响。我们得出结论，CV - 4151可改善缺血后脑灌注不足，且这种改善与矢状窦中TxB2水平降低有关。
