THE EFFECT OF HEPATOCYTE ENLARGEMENT ON THE HEMODYNAMIC CHARACTERISTICS OF THE ISOLATED-PERFUSED RAT-LIVER PREPARATION

The influence of hepatocyte enlargement on intrahepatic hemodynamics w as assessed in the isolated perfused rat liver preparation (IPRL) usin g two experimental models: hypotonic liver cell swelling and phenobarb itone-induced hepatocyte hypertrophy. The analysis of pressure-flow da ta obtained from the portal vascular bed over a flow range of 0 to 70 mL/min in the presence of a maximally-effective concentration of the v asodilator agent papaverine hydrochloride (6 x 10(-4) mol/L) enabled t he calculation of P-0, an estimate of the pressure required to passive ly distend the intrahepatic vasculature, and G(max), the maximal porta l vascular conductance, By comparison with an isotonic perfusion mediu m (Krebs-Henseleit buffer [KH] containing 2.5% bovine serum albumin [B SA]), perfusion with a hypotonic medium induced a significant increase in mean hepatocyte cross-sectional area (HA) (590 +/- 21 vs. 324 +/- 23 mu m(2), P < .05), a fall in G(max) (0.39 +/- 0.08 vs, 2.02 +/- 0.1 8 mL/min/g/mm hg, P < .001), and an increase in P-0 (2.96 +/- 0.38 vs, 1.58 +/- 0.07 mm hg, P < .001). Phenobarbitone administered in drinki ng water (0.5 g/L) over a period of 60 days also induced a significant degree of hepatocyte enlargement (H-A, 510 +/- 29 mu m(2), P < .05). On day 7, portal pressure measured in vivo in this group was significa ntly elevated compared with untreated controls (10.5 +/- 0.3 vs. 8.4 /- 0.2 mm hg, P < .001), while in the IPRL G(max) was reduced (0.48 +/ - 0.01 mL/min/g/mm hg, P < .001), and P-0 was increased (2.23 +/- 0.17 mm hg, P < .05). However, with continued phenobarbitone treatment por tal pressure, G(max) and P-0 returned toward control values. The resul ts confirm that hepatocyte enlargement is associated with a significan t disturbance of intrahepatic hemodynamics but also that some adaptati on occurs if hepatocyte enlargement is sustained over a prolonged peri od of time.