ROLE OF THE HEPATIC-ARTERY IN THE METABOLISM OF PHENACETIN AND ACETAMINOPHEN - AN INTRAVITAL MICROSCOPIC AND MULTIPLE-INDICATOR DILUTION STUDY IN PERFUSED-RAT-LIVER

We studied the pattern of intermixing of the hepatic arterial and port al venous flows in a perfused rat liver preparation under constant flo w (12 ml/min) with intravital epifluorescent microscopy; changes in th e steady state extraction ratio of carbon 14-labeled phenacetin and tr itiated acetaminophen, probes metabolized primarily in perivenous and periportal regions of the rat liver, respectively; and the spaces acce ssed by noneliminated reference indicators introduced as a bolus into the hepatic artery and portal vein at different hepatic arterial/porta l venous flow regimens of 0:12, 2:10 and 4:8. The sinusoidal velocitie s for the hepatic arterial- and portal venous (hepatic arterial/portal venous how at 4:8)-infused fluorescein isothiocyanate-erythrocytes (1 00 mu l/min) were 327 +/- 78 and 301 +/- 63 mu m/sec, respectively, an d the velocity for the solely portal venous-perfused liver (12 ml/min) was 347 +/- 74 mu m/sec; the how-weighted sinusoidal velocity was hig hly correlated to the sinusoidal volume for the dually perfused rat li ver. Small but significant decreases in the extraction ratio of [C-14] phenacetin (from 0.989 to 0.984 and 0.980) and tritiated acetaminophen (from 0.631 to 0.607 to 0.563), delivered simultaneously into the hep atic artery and portal vein, were observed with an increment of hepati c arterial how within the same liver preparation; oxygen consumption r ate also fell slightly, in parallel fashion. When a multiple-indicator dilution dose containing chromium 51-labeled RBCs, iodine 125-labeled albumin and tritiated water or [C-14]urea was injected into the hepat ic artery (which accesses both the peribiliary capillary plexus [nonsi nusoidal] and the sinusoidal bed) and portal vein (which enters only t he sinusoids) at 10-min intervals within each steady state, the blood volume, total albumin space, albumin Disse space, total water and pare nchymal cellular water spaces were unchanged after portal venous injec tion for all hepatic arterial/portal venous flow ratios, suggesting th at the arterial how is ineffective in perturbing average sinusoidal ho w dynamics. However, slightly larger total water spaces were obtained with hepatic arterial injection. This excess water space was almost co mpletely accounted for by the ''nonsinusoidal'' extravascular space as sociated with the peribiliary capillary plexus; it averaged 0.03 ml/gm and was independent of flow. The anomaly, a reduced flow-weighted sin usoidal velocity for the dually perfused liver, an unchanged diameter of the terminal hepatic venule (32 mu m) among the hepatic arterial/po rtal venous flow ratios and the reduction in the extraction ratio of t he drug probes and oxygen consumption rates suggest that some of the a rterial flow must have entered the sinusoids somewhat downstream.