Successful treatment of CCl4-induced acute liver failure with portal vein arterialization in the rat.
BACKGROUND
Optimization of the conditions for regeneration is a major goal in the management of patients with acute liver failure (ALF). Previous observations suggested that hyperoxygenation of the liver may improve its regenerative capacity. Thus, this study aimed to determine whether an additional supply of oxygenated blood achieved by portal vein arterialization (PVA) is protective in rat ALF caused by toxin administration or hepatectomy.


METHODS
Sprague-Dawley rats were subjected or not to PVA after CCl(4) intoxication or extended hepatectomy. PVA was performed by interposing a stent between the left renal artery and splenic vein after left nephrectomy and splenectomy. Liver injury was evaluated by the serum ALT level and necrotic cell count. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine (BrdU) staining. The 10-day survival was assessed in separate experimental groups.


RESULTS
The pO(2) in portal blood increased significantly following PVA. In the CCl(4)-induced ALF, serum ALT levels and necrosis were significantly reduced in arterialized than non-arterialized rats. PVA greatly promotes liver regeneration in both models. Finally, PVA significantly improved survival compared to controls (CCl(4): 100 versus 40%; 90% hepatectomy: 90 versus 30%). Interestingly, in the CCl(4)-induced ALF, survival was 100% even when the shunt was closed after 48 h.


CONCLUSIONS
These data indicate that the additional supply of arterial oxygenated blood through PVA promotes a rapid regeneration leading to the resolution of toxic-induced massive liver necrosis and a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool for optimizing hepatocyte regeneration.
Nardo
Bruno
B
Department of Surgery, Intensive Care and Transplantation, University of Bologna, Bologna, Italy. nardo@aosp.bo.it
Caraceni
Paolo
P
Puviani
Lorenza
L
Pertosa
Anna Maria
AM
Domenicali
Marco
M
Pariali
Milena
M
Angiolini
Graziella
G
Chieco
Pasquale
P
Trevisani
Franco
F
Bernardi
Mauro
M
Cavallari
Antonino
A
D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003401:Creatine / Q000097:blood; D006498:Hepatectomy; D019044:Image Cytometry; D007150:Immunohistochemistry; D008102:Liver Circulation; D017093:Liver Failure / Q000139:chemically induced* / Q000473:pathology / Q000601:surgery*; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D010100:Oxygen / Q000097:blood; D011169:Portal Vein / Q000601:surgery*; D011517:Prothrombin Time; D051381:Rats; D017207:Rats, Sprague-Dawley
D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003401:Creatine; D010100:Oxygen