EFFECTS OF TCV-309, A NOVEL PAF ANTAGONIST, ON CIRCULATORY SHOCK AND HEMATOLOGICAL ABNORMALITY INDUCED BY ENDOTOXIN IN DOGS

We investigated the effects of TCV-309, a novel platelet activating fa ctor (PAF) antagonist, on circulatory dysfunction and hematological ab normalities in experimental canine endotoxin (ET) shock. ET caused bip hasic hypotension with a decrease in cardiac output (CO), left ventric ular systolic pressure (LVP) and its dp/dt(max). The first hypotensive phase occurred within 15 min, and the second phase between 90 and 180 min following the injection of ET. Pulmonary vascular resistance (PVR ) abruptly increased at 15 min with a partial recovery, and was then s ustained at twice the basal value throughout the experiment. TCV-309 a ttenuated the hypotension, the decrease in CO, LVP and its dp/dt(max), and the increase in PVR. TCV-309 had no significant effect on the inc rease in TPR. The decrease in plasma fibrinogen and the increase in he matocrit and plasma lactate were significantly attenuated by TCV-309. These data suggest that PAF may be a key mediator leading to shock in sepsis.