The Clearance Rate of Chylomicron Retinyl Ester from Plasma Can Be Used to Distinguish Rats with Cirrhosis from Those with Portacaval Shunt

Abstract

Effects of carbon tetrachloride treatment and portacaval shunt surgery on exogenous chylomicron retinyl ester clearance from rat plasma were analyzed assuming three-compartment model kinetics. In rats with cirrhosis and in those with Eck fistulas, the relative pool size of compartment 2 decreased (0.20 and 0.36, respectively) compared with controls (0.82). The relative mass of compartment 3 significantly increased in rats with cirrhosis (1.55) or Eck fistula (0.19) compared with control rats (0.11). The cirrhotic and Eck fistula groups were indistinguishable on the basis of these parameters and on the basis of indocyanine green test values. However, the cirrhosis and Eck fistula groups differed clearly from each other with respect to fractional efflux rate constants (l2, l3), where the constant l2 is from compartment 2 and the l3 is from compartment 3. Both values decreased in cirrhotic rats, suggesting that the hepatic uptake of chylomicron retinyl esters was impaired by carbon tetrachloride. On the other hand, Eck fistula rats did experience dramatic increases in l3, implying that the hepatic uptake of chylomicron retinyl esters from compartment 3 was enhanced by portacaval shunting. Elevation of the plasma estrogen level observed in Eck fistula rats may be responsible for the induction of low-density lipoprotein receptors on hepatocytes and for the subsequent enhancement of l3. These results suggest that a three-compartment model of plasma retinyl ester disappearance kinetics gives important quantitative information about hepatic function. Clinical application of the chylomicron retinyl ester clearance test is discussed for estimating hepatic function reserves and for differential diagnosis of portal hypertension.