Hepatocellular dysfunction after severe hypotension in the absence of blood loss is associated with the increased IL-6 and PGE(2)

Although hepatocellular dysfunction occurs following trauma and hemorrhagic shock, whether severe hypotension even in the absence of blood loss depres ses hepatocellular function remains unknown. The aim of this study, therefo re, was to determine whether chemically induced severe hypotension causes h epatocellular dysfunction and, if so, whether IL-6 and PGE(2) are associate d with this dysfunction. To study this, hypotension was induced in adult ma le rats by intravenous infusion of a high dosage of ATP-MgCl2 solution (3.2 +/- 0.45 mu mol/min/kg body wt) for 60 min. Blood pressure decreased from 108 +/- 6 mm Hg to an average of 43 mm Hg during the infusion period and re turned to normal levels immediately after the completion of ATP-MgCl2 infus ion. At 0 and 4 h after hypotension, hepatocellular function [i.e., maximum velocity of indocyanine green clearance (V-max) and its efficiency (K-m)] was measured using a fiberoptic catheter and in vivo hemoreflectometer. Car diac output was determined by dye dilution. Microvascular blood flow was as sessed by laser Doppler flowmetry. Plasma levels of PGE(2) and IL-6 were me asured by radioimmunoassay and bioassay, respectively. The results indicate that severe hypotension in the absence of any blood loss depresses hepatoc ellular function (i.e., decreased V-max and K-m) despite stable cardiac out put and hepatic perfusion at 6 and 4 h after the completion of hypotension. Moreover, severe hypotension resulted in significantly increased plasma le vels of PGE(2) (only at 0 h) and IL-6. Thus, chemically induced severe hypo tension in the absence of any blood loss, which does not significantly redu ce cardiac output and hepatic perfusion, depresses hepatocellular function and upregulates IL-6 and PGE(2) production. (C) 1998 Academic Press.