The effect of consecutively larger doses of L-arginine on hepatic microcirculation and tissue oxygenation in hepatic steatosis.
BACKGROUND
Impairment of hepatic microcirculation in fatty liver is thought to render it more susceptible to the effects of ischaemia-reperfusion injury as compared to non-fatty liver grafts. The present study aimed to investigate the effect of consecutively larger doses of L-arginine on the hepatic microcirculation and tissue oxygenation of fatty liver.


METHODS
Sprague-Dawley rats (200-250 g) were fed a liquid ethanol diet to induce hepatic steatosis or a normal diet for 6 weeks. Hepatic blood flow, microcirculation, tissue oxyhaemoglobin (HBO(2)) in response to consecutive intravenous bolus administrations of l-arginine (50 mg/kg, 100 mg/kg, 300 mg/kg and 500 mg/kg) or normal saline, were assessed.


RESULTS
Baseline hepatic arterial flows and hepatic microcirculation values were significantly lower in steatotic livers vs. control livers. L-arginine significantly improved hepatic arterial, portal venous blood flow, hepatic microcirculation and tissue oxygenation in both fatty and control livers.


CONCLUSIONS
The administration of NO in cumulatively larger doses is effective at improving hepatic blood flow, microcirculation and hepatic tissue oxygenation in steatotic liver and these results could form the basis of further work into using NO as a therapeutic tool to reclaim moderately steatotic grafts for use in liver transplantation.
Ijaz
Samia
S
Hepatic Haemodynamic Laboratory, Academic Division of Surgical and Interventional Sciences, University College London, London NW3 2PF, UK. samiaijaz@hotmail.com
Winslet
Marc C
MC
Seifalian
Alexander M
AM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000378:metabolism / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008099:Liver / Q000098:blood supply* / Q000187:drug effects*; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011169:Portal Vein / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow
D009569:Nitric Oxide; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester