Thromboxane A2 (TXA2) and
endothelin-1 (ET-1) have been proposed as the important
vasoconstrictors that increase portal venous resistance in paracrine or autocrine fashion. We hypothesized that the hepatic damage following
trauma-
hemorrhage (T-H) is induced by the impaired hepatic circulation due to the increased production of
vasoconstrictors such as ET-1 and TXA2 by the liver. To test this, male Sprague-Dawley rats (n = 6/group) were subjected to
trauma (i.e., midline
laparotomy) and
hemorrhage (35-40 mmHg for 90 min followed by fluid
resuscitation) or
sham operation. At 2 or 5 h after the end of
resuscitation, the liver was isolated and perfused and portal inflow pressure, bile flow, and release of ET-1 and
thromboxane B2 (TXB2; a stable metabolite of TXA2) into the perfusate were measured. The level of portal pressure was higher at 5 h following T-H compared with 2 h after T-H and
sham. The portal pressure was inversely correlated to the amount of bile production. Furthermore, the bile flow was significantly correlated to the hepatic damage as evidenced by release of
lactate dehydrogenase into the perfusate. The level of ET-1 at 5 h following T-H in the perfusate after 30 min of recirculation did not show any difference from
sham. However, the levels of TXB2 in the T-H group were significantly higher than those in
sham at that interval. These results indicate that the increased release of TXA2 but not ET-1 following T-H might be responsible for producing the increased portal resistance, decreased bile production, and hepatic damage.