Pathophysiology of dogs after 84% hepatectomy with emphasis on prostaglandin metabolites and the effect of a thromboxane A2 synthesis inhibitor and a prostaglandin I2 analog.
The pathophysiological conditions following 84% hepatectomy were examined in terms of the changes in thromboxane A2 (TxA2) and prostaglandin I2 (PGI2) in a canine model. OKY-046, a TxA2 inhibitor, and OP-2507, a PGI2 analog, were administered to evaluate the possibility of extending hepatic resection. The 2-week survival rate following 84% hepatectomy significantly improved after the administration of OKY-046 and OP-2507, from 12.5% to 58.3% and 75.0%, respectively. Furthermore, OP-2507 significantly improved impaired hepatocyte and sinusoidal endothelial cell function after 84% hepatectomy, resulting in a satisfactory recovery to the preoperative levels. Within 24 h after 84% hepatectomy, the plasma levels of thromboxane B2 (TxB2) increased significantly, and the 6-keto-prostaglandin F1 alpha (6-KF) levels became slightly elevated. OKY-046 and OP-2507 decreased TxB2 and increased 6-KF in the plasma, resulting in the maintenance of sufficient blood flow in the portal vein and hepatic tissue and the mitigation of microcirculatory disorders. Moreover, the cytoprotective effects of the two drugs inhibited functional impairment of the residual liver. In conclusion, abnormal prostaglandin metabolites were produced after 84% hepatectomy, being involved in residual liver disorders. However, the administration of either an inhibitor of TxA2 synthesis or a PGI2 analog ameliorated the functional impairment of the residual liver, which suggests their potential value for extending the resectability of the liver from what is presently feasible.
Iwata
M
M
First Department of Surgery, Mie University School of Medicine, Japan.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000378:metabolism; D000818:Animals; D002423:Cause of Death; D004285:Dogs; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006498:Hepatectomy; D006633:Histamine Antagonists / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008111:Liver Function Tests; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D011453:Prostaglandins / Q000097:blood / Q000378:metabolism*; D011863:Radioimmunoassay; D015996:Survival Rate; D013929:Thromboxane B2 / Q000097:blood / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors
D006633:Histamine Antagonists; D008689:Methacrylates; D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C049453:OP 2507; D006820:Hyaluronic Acid; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C034364:ozagrel