Change in serum hyaluronan: a simple index of short-term drug-induced changes in hepatic sinusoidal perfusion.
BACKGROUND
Hyaluronan is an endogenous polysaccharide whose clearance from the plasma is predominantly by liver sinusoidal cells and is sinusoidal flow dependent. This study was designed to determine if a change in serum hyaluronan might reliably reflect short-term drug-induced changes in sinusoidal perfusion.


METHODS
Hemodynamic changes following an oral dose of ketanserin were compared with changes in serum hyaluronan levels in 12 patients with alcoholic liver disease and portal hypertension. Indices determined comprised heart rate, mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance, hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and extraction, and total hepatic blood flow. Measurements were made in a basal state 1 hour after ketanserin ingestion and expressed as a ratio of values post- to pre-ketanserin administration.


RESULTS
Ketanserin had variable effects comprising both increases and decreases in all indices. On univariate and multivariate analysis, changes in serum hyaluronan concentration (1.05 +/- 0.13, mean +/- SD) significantly correlated with only one index: changes in ICG clearance (0.93 +/- 0.17, r = -0.65, P = 0.02).


CONCLUSIONS
Changes in serum hyaluronan levels reflect short-term drug-induced changes in sinusoidal perfusion in patients with alcoholic liver disease and portal hypertension. Serial measurement of serum hyaluronan levels may offer a simple method of screening vasoactive drugs for their short-term effects on sinusoidal perfusion.
Gibson
P R
PR
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Victoria.
Fraser
J R
JR
Colman
J C
JC
Jones
P A
PA
Jennings
G
G
Dudley
F J
FJ
D000368:Aged; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D007650:Ketanserin / Q000494:pharmacology*; D008102:Liver Circulation / Q000187:drug effects*; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis
D006820:Hyaluronic Acid; D007650:Ketanserin