Liver function improvement following increased portal blood flow in cirrhotic rats.
OBJECTIVE
Liver microcirculation in cirrhosis is characterized by development of intrahepatic shunts and capillarization of sinusoids secondary to cell necrosis and deposition of new collagen, resulting in both decreased drug elimination and increased vascular resistance with portal hypertension. The aim of this study was to examine the effects of increased portal blood flow on hepatic microcirculation and drug elimination in 13 perfused livers from cirrhotic rats.


METHODS
Intrahepatic resistance was assessed under basal conditions (21.2 +/- 0.3 mL/min) and 1 hour after doubling the flow (41.6 +/- 1.0 mL/min). A multiple indicator dilution technique was used at both flow rates to measure sinusoidal volume, albumin and sucrose extravascular volumes, and cellular water volume. Hepatic elimination of labeled taurocholate and propranolol was also measured, and the recovery of 15-microns microspheres was used to evaluate large intrahepatic shunts.


RESULTS
After doubling the flow, intrahepatic resistance decreased by 31%. Sinusoidal and extravascular volume increased significantly without a change in microsphere recovery. However, there was a marked increase in taurocholate and propranolol elimination by cirrhotic livers. Moreover, during high flow, significant correlations were found between changes in albumin extravascular volume and taurocholate and propranolol elimination.


CONCLUSIONS
Increased portal blood flow in cirrhotic rats induces a decrease in intrahepatic resistance without changes in intrahepatic shunting and improves drug elimination by the liver without deleterious effects on hepatocyte viability.
Centre de Recherche Clinique André-Viallet, Hôpital Saint-Luc, Université de Montréal, Canada.
J E
JE
Cardoso
L
L
Giroux
I
I
Kassissia
D
D
Houssin
N
N
Habib
P M
PM
Huet
D000818:Animals; D002470:Cell Survival; D066298:In Vitro Techniques; D007201:Indicator Dilution Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008102:Liver Circulation; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation; D011169:Portal Vein / Q000503:physiopathology*; D011433:Propranolol / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013656:Taurocholic Acid / Q000493:pharmacokinetics; D014655:Vascular Resistance
D013656:Taurocholic Acid; D011433:Propranolol