On the mechanisms responsible for selection of hepatic veins as target for thrombosis following injection of endotoxin in hyperlipemic rats.
The feeding of a butter-rich diet, to sensitize rats for studying the phenomenon of hepatic vein thrombosis, is shown to produce severe liver steatosis leading to a sinusoidal barrage and portal hypertension. The portal pressure in these animals was 210 +/- 4 mm of saline, as compared to 113 +/- 3 mm in the normal rat. Blood circulation studies using carbon suspensions revealed production of a vascular stasis in the hepatic veins after 60 to 90 minutes, when endotoxin (Salmonella typhosa, 0.3 mg/kg) is introduced into the blood circulation to initiate hepatic vein thrombosis. Similar results were observed after 15 minutes with ellagic acid (1 mg/kg/min). The stasis was found in connection with an additional intrahepatic resistance to blood flow as evidenced by a rise in portal pressure and by a reduction in liver perfusion in relation with development of systemic hypotension. In contrast with this, endotoxin initiated only slight and transient changes in the normal rat. Thrombosis immediately followed production of stasis in the hepatic vein, whether the phenomenon was initiated by endotoxin or ellagic acid. Furthermore, inhibition of the vascular stasis of alpha-adrenergic blockade (phenoxybenzamine, 3 mg/kg) was accompanied by prevention of hepatic vein thrombosis. It is concluded that stasis in the hepatic veins resulting from a mechanical obstruction of the circulation by steatosis and by an additional reduction in blood flow initiated by endotoxin, is responsible for selection of hepatic veins as targets for thrombosis following injection of endotoxin in hyperlipemic rats.
D000818:Animals; D001578:Benzopyrans; D001794:Blood Pressure / Q000187:drug effects; D002079:Butter; D004036:Diet, Atherogenic; D004041:Dietary Fats; D004731:Endotoxins; D005234:Fatty Liver / Q000209:etiology / Q000473:pathology; D006487:Hemostasis / Q000187:drug effects; D006490:Hemostatics; D006503:Hepatic Veins; D006949:Hyperlipidemias / Q000209:etiology* / Q000473:pathology; D006975:Hypertension, Portal / Q000209:etiology; D008099:Liver / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D012485:Salmonella typhi; D013924:Thrombophlebitis / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D014655:Vascular Resistance / Q000187:drug effects
D001578:Benzopyrans; D004041:Dietary Fats; D004731:Endotoxins; D006490:Hemostatics; D010643:Phenoxybenzamine; D002079:Butter