Fukuoka T, Nakajima Y, Nakano H
First Department of Surgery, Nara Medical University, Japan.
Surg Today. 1995;25(4):351-6. doi: 10.1007/BF00311259.
Liver failure is often accompanied by shock, which is usually refractory to conventional vasopressive therapy, and it is believed that some potent chemical mediators are involved in this process. The platelet activating factor (PAF) is a newly discovered inflammatory mediator that has a remarkable hypotensive action. In the present study, the possible role of PAF in shock after ischemic liver failure was investigated. Partial hepatic ischemia was induced in Wistar rats by clamping the hepatic afferent vessels to almost 70% of the whole liver for 90 min. One group of rats was pretreated with 10 micrograms/kg of TCV-309, a PAF antagonist. Pretreatment with TCV-309 inhibited the shock that ultimately occurred in the untreated rats; the survival rate 16 h after hepatic ischemia was 20% in the untreated control group but 100% in the group pretreated with TCV-309. The level of PAF in the plasma after hepatic ischemia was 2,939 +/- 2,412 pg/ml, which was significantly higher than that of the surgical control (920 +/- 188 pg/ml). These findings strongly suggest that anoxical disintegration of the liver derives PAF which causes shock. Thus, a PAF antagonist is expected to be an effective prophylactic treatment for patients who are at risk of developing shock from an ischemic liver.
肝衰竭常伴有休克，而这种休克通常对传统的血管加压治疗无效，人们认为一些强效化学介质参与了这一过程。血小板活化因子（PAF）是一种新发现的炎症介质，具有显著的降压作用。在本研究中，研究了PAF在缺血性肝衰竭后休克中的可能作用。通过夹闭肝传入血管使Wistar大鼠的部分肝脏缺血达到全肝的近70%，持续90分钟。一组大鼠用10微克/千克的PAF拮抗剂TCV-309进行预处理。用TCV-309预处理可抑制未处理大鼠最终发生的休克；肝缺血后16小时，未处理对照组的存活率为20%，而用TCV-309预处理组的存活率为100%。肝缺血后血浆中PAF的水平为2939±2412皮克/毫升，显著高于手术对照组（920±188皮克/毫升）。这些发现强烈表明，肝脏的缺氧性崩解产生了导致休克的PAF。因此，PAF拮抗剂有望成为对有因缺血性肝脏而发生休克风险的患者的一种有效预防性治疗方法。
