Effect of cold ischemia-warm reperfusion on the cirrhotic rat liver.
Cirrhosis is known to induce capillarization of the sinusoidal endothelial cells (SECs) and collagenization of the space of Disse, resulting in a reduced access of plasma and plasma-dissolved substances to hepatocytes due to their limited diffusion in the extravascular space. The aim of the present study was to use a well known effect of cold ischemia-warm reperfusion (CI-WR) on liver SECs, that is, their retraction and detachment, progressing to a denudation of the SEC lining. The disappearance of the capillarized SEC lining would improve the access of plasma and plasma-dissolved substances to the hepatocytes and consequently might improve the metabolic function of cirrhotic livers. This study was performed using the isolated perfused rat liver model subjected to 24-hour CI followed by a 60-minute WR in thioacetamide-induced cirrhosis. Liver microcirculation was evaluated using the multiple indicator dilution curve (MIDC) technique. Hepatocyte, SEC, and Kupffer cell functions were evaluated using specific elimination processes. As occurs in normal livers, CI-WR induced extensive SEC necrosis with a marked reduction of the hyaluronic acid elimination. By contrast, the hepatic microcirculation was not modified: vascular, extravascular, and the cellular spaces were similar before and following CI-WR. In addition, the hepatic metabolic functions, as evaluated by propranolol and taurocholate hepatic uptake, were neither improved nor decreased, as were Kupffer cell functions. The present data strongly suggest that capillarization of SECs plays a lesser role than collagenization of the space of Disse in the reduced exchange between sinusoids and hepatocytes in thioacetamide-induced cirrhotic rat livers, which appear to be quite resistant to CI-WR.
Huet
Pierre-Michel
PM
Institut National de la Santé et de la Recherche Médicale U568, Liver Unit, Faculté de Médecine, Université de Nice Sophia Antipolis, Nice, France. huet.p@chu-nice.fr
Giroux
Lise
L
Laurens
Marina
M
Crenesse
Dominique
D
D000082:Acetaminophen; D000818:Animals; D001646:Bile / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D007511:Ischemia / Q000503:physiopathology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D008297:Male; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion
D000082:Acetaminophen; D007770:L-Lactate Dehydrogenase