Alteration of hepatic microcirculation by oxethazaine and some vasoconstrictors in the perfused rat liver.
We previously reported that, in isolated perfused rat livers in a constant flow system, oxethazaine (OXZ) rapidly increased portal pressure (PP) accompanied by inhibition of oxygen uptake and the subsequent metabolic effects. In this study, hemodynamic changes were studied by using an indicator dilution technique and by microscopic observation of post-fixed liver samples stained with acridine orange or trapped fluorescence microspheres (FMSs). During the increase in PP induced by OXZ, the mean transit times of both red blood cells and azoalbumin were shortened markedly, and the vascular and extravascular albumin spaces decreased to 55 and 18% of the controls, respectively. With acridine orange, in the control livers, all the dye infused was taken up and the periportal zones were uniformly stained over all the liver sections, whereas in the OXZ-treated livers, about 30% of the dye drained out, and extensive staining was observed in the central portion of the liver mass, but the peripheral portions of the liver were much less stained. The staining was often localized around large portal vein branches and spread toward the hepatic veins. These changes were recoverable in the absence of OXZ. Distributions of 1-microm and 15-microm FMSs were likewise altered by OXZ. Thus, uneven perfusion may be the primary cause of decreased tissue spaces and also of the metabolic effects produced by OXZ. Endothelin 1 also produced OXZ-like changes, while U-46619 had lesser effects. The methodology used in this study may help delineate the hepatic perfusion disturbance caused by various vasoconstrictors.
Masuda
Y
Y
Division of Toxicology, Niigata College of Pharmacy, Kami-shinéi-cho, Japan.
Ozaki
M
M
Oguma
T
T
D000165:Acridine Orange; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004396:Coloring Agents; D004983:Ethanolamines / Q000494:pharmacology*; D005453:Fluorescence; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000648:ultrastructure; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004396:Coloring Agents; D004983:Ethanolamines; D014662:Vasoconstrictor Agents; D000165:Acridine Orange; C100289:oxethazaine