Role of thromboxane in producing portal hypertension following trauma-hemorrhage.
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.
Yokoyama
Yukihiro
Y
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
Toth
Balazs
B
Kitchens
William C
WC
Schwacha
Martin G
MG
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000007:Abdominal Injuries / Q000150:complications*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001646:Bile / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D006470:Hemorrhage / Q000150:complications* / Q000209:etiology; D006975:Hypertension, Portal / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver; D008297:Male; D010477:Perfusion; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism; D014690:Venous Pressure; D014950:Wounds, Penetrating / Q000150:complications
D019332:Endothelin-1; D013929:Thromboxane B2; D013928:Thromboxane A2; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase