tcv-309 and Shock

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.

Topics: Animals; Hypotension; Ischemia; Isoquinolines; Liver; Liver Failure; Male; Platelet Activating Factor; Pyridinium Compounds; Rats; Rats, Wistar; Shock; Tetrahydroisoquinolines