Fukuoka T, Nakajima Y, Matsumoto M, Segawa M, Kanehiro H, Hisanaga M, Wada T, Nakano H
First Department of Surgery, Nara Medical University, Japan.
Life Sci. 1990;47(6):565-70. doi: 10.1016/0024-3205(90)90617-z.
Platelet activating factor (PAF) is a newly discovered inflammatory chemical mediator, which was reported to play a pivotal role in various types of shock. There is also a great possibility that PAF plays an important role in the shock caused by hepatic inflow occlusion. In the present study, the effect of CV6209, a PAF antagonist, on the shock caused by the occlusion was investigated. Intravenous 3 micrograms/kg of PAF caused hypotension in Wistar rats (n=6), and pretreatment with intravenous 3 mg/kg of CV6209 significantly (p less than 0.01) prevented the hypotension (n=6). Forty-five minutes of hepatic inflow occlusion caused hypotension in rats during the occlusion period, and the hypotension continued even after restoration of blood flow in control group (pretreated with saline i.v. only, n=5). In contrast, this hypotension was significantly (p less than 0.01) reversed in PAF antagonist group (pretreated with 3 mg/kg of CV6209 i.v., n=5). In sham-operated rats (n=6), arterial pressure remained unchanged and not hypotensive during the monitoring period. The survival rate of rats 90 minutes after declamp was 30% in control group (n=20), and that was significantly (p less than 0.05) improved to be 65% in PAF antagonist group (n=20). In conclusion, PAF plays an important role in the shock and death caused by temporary hepatic inflow occlusion, and a PAF antagonist could be a therapeutic drug against temporary hepatic inflow occlusion.
血小板活化因子（PAF）是一种新发现的炎症化学介质，据报道它在各种类型的休克中起关键作用。PAF在肝血流阻断所致休克中发挥重要作用的可能性也很大。在本研究中，研究了PAF拮抗剂CV6209对肝血流阻断所致休克的影响。静脉注射3微克/千克的PAF可导致Wistar大鼠（n = 6）低血压，而静脉注射3毫克/千克的CV6209预处理可显著（p < 0.01）预防低血压（n = 6）。45分钟的肝血流阻断在阻断期间导致大鼠低血压，并且在对照组（仅静脉注射生理盐水预处理，n = 5）中即使恢复血流后低血压仍持续。相比之下，在PAF拮抗剂组（静脉注射3毫克/千克的CV6209预处理，n = 5）中，这种低血压得到显著（p < 0.01）逆转。在假手术大鼠（n = 6）中，监测期间动脉压保持不变，未出现低血压。对照组（n = 20）夹闭后90分钟大鼠的存活率为30%，而PAF拮抗剂组（n = 20）的存活率显著（p < 0.05）提高到65%。总之，PAF在暂时性肝血流阻断所致的休克和死亡中起重要作用，PAF拮抗剂可能是一种治疗暂时性肝血流阻断的药物。
