Nitric oxide reduces organ injury and enhances regeneration of reduced-size livers by increasing hepatic arterial flow.
BACKGROUND
Reduced-size livers suffer from portal hyperperfusion, diminished arterial blood flow and the risk of postoperative liver injury. The aim of this experimental study was to unravel the role of nitric oxide in this setting.


METHODS
Rats underwent 85 per cent partial hepatectomy and either substitution of nitric oxide with molsidomine or inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine methyl ester. Untreated hepatectomized animals served as controls and unresected animals as the sham group.


RESULTS
Ultrasonic flowmetry following partial hepatectomy revealed a marked increase in portal venous inflow with a concomitant decrease in hepatic arterial inflow. Nitric oxide substitution counteracted the decline in hepatic arterial inflow and caused a significantly greater increase in cell proliferation after partial hepatectomy compared with control or NOS-inhibited animals. Hepatectomized animals further profited from nitric oxide substitution, as indicated by reduced aminotransferase release and improved liver function.


CONCLUSIONS
Nitric oxide improves the postoperative course of rats with reduced-size livers by modulating hepatic macrohaemodynamics and mediating regeneration and cytoprotection, but not by reducing hepatic hyperperfusion and the accompanying sinusoidal shear stress.
Cantré
D
D
Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
Schuett
H
H
Hildebrandt
A
A
Dold
S
S
Menger
M D
MD
Vollmar
B
B
Eipel
C
C
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006498:Hepatectomy; D006499:Hepatic Artery / Q000187:drug effects*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D007150:Immunohistochemistry; D008102:Liver Circulation / Q000187:drug effects*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008981:Molsidomine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011184:Postoperative Period; D051381:Rats; D017208:Rats, Wistar
D045462:Endothelium-Dependent Relaxing Factors; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D001219:Aspartate Aminotransferases; D019331:NG-Nitroarginine Methyl Ester