Protective Effect of Nitric Oxide on Liver Circulation from Ischemia Reperfusion Injury.
BACKGROUND
The reduction of endogenous nitric oxide (NO) production during hepatic ischemia-reperfusion injury, generally via a reduction in endothelial NO synthase activity, leads to liver injury. We hypothesized that administration of an exogenous NO donor into the portal vein may ameliorate hepatic blood flow reduction after a period of ischemia.


METHODS
A total of 90 min of ischemia (portal vein and hepatic artery) was applied in 15 anesthetized pigs, using the Pringle method under sevoflurane anesthesia. All animals were administered either saline (control group, n = 8) or sodium nitroprusside (SNP, n = 7) as exogenous NO donor drugs into the portal vein, 30 min before and after ischemia. The portal venous blood flow and hepatic artery blood flow were measured continuously using transonic flow probes attached to each vessel. Endogenous NO (NOx = NO2- + NO3-) production was measured every 10 min using a microdialysis probe placed in the left lobe of the liver.


RESULTS
In the SNP group, portal venous flow remained unchanged and hepatic artery flow significantly increased compared to baseline. Although the production of liver tissue NOx transiently decreased to 60% after ischemia, its level in the SNP group remained higher than the control saline group.


CONCLUSIONS
Regional administration of SNP into the portal vein increases hepatic arterial flow during ischemia reperfusion periods without altering mean systemic arterial pressure. We speculate that administration of an exogenous NO donor may be effective in preventing liver injury via preservation of total hepatic blood flow.
a Divisions of Clinical Physiology, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan.
Watanabe
W
Toshihiro
a Divisions of Clinical Physiology, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan.
Shinji
S
Kurata
a Divisions of Clinical Physiology, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan.
Sanuki
S
Takuro
a Divisions of Clinical Physiology, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan.
Okayasu
O
Ichiro
b Oral Pathology, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan.
Shibata
S
Yasuaki
b Oral Pathology, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan.
Toru
T
Ikeda
c Anesthesiology, Course of Medical and Dental Sciences, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan.
Hiroyuki
H
Ureshino
a Divisions of Clinical Physiology, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan.
Takao
T
Ayuse
D000818:Animals; D004353:Drug Evaluation, Preclinical; D006499:Hepatic Artery / Q000187:drug effects; D019194:Ischemic Preconditioning / Q000379:methods; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D008107:Liver Diseases / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D009599:Nitroprusside / Q000008:administration & dosage*; D011169:Portal Vein; D011897:Random Allocation; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine
D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide
ischemia reperfusion; nitric oxide; hepatic arterial buffer response; pig; pharmacological preconditioning; HPLC