Novel nitric oxide donor (FK409) ameliorates liver damage during extended liver resection with warm ischemia in dogs.
BACKGROUND
Nitric oxide attenuates ischemia-reperfusion injury by maintaining organ circulation through its actions as a vasoregulator, an inhibitor of platelet aggregation, and an attenuator of leukocyte adhesion. Otherwise, the harmful effects of enhanced nitric oxide production induced by inducible nitric oxide synthase mediate ischemia-reperfusion injury. FK409 has been characterized as a spontaneous nitric oxide donor. The aim of this study was to evaluate the effects of FK409 on extended liver resection with ischemia using a canine model.


METHODS
Adult mongrel dogs were subjected to 60 minutes of warm ischemia by partial inflow occlusion. After reperfusion the nonischemic lobes were resected and the remnant liver function was evaluated. The dogs were divided into two groups: the control group (n = 7) and the FK409 group (n = 6), which was given FK409 through the portal vein.


RESULTS
The hepatic tissue blood flow, serum liver enzymes levels, and serum endothelin-1 level after reperfusion were significantly better in the FK409 group than in the control group. Electron microscopy demonstrated that endothelial cells and Ito cells were well-preserved in the FK409 group. The 3-day survival rate was statistically better in the FK409 group (67%) than in the control group (14%).


CONCLUSIONS
FK409 appears to have protective effects during extended liver resection with ischemia.
Aiba
M
M
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Takeyoshi
I
I
Ohwada
S
S
Kawashima
Y
Y
Iwanami
K
K
Sunose
Y
Y
Yamada
T
T
Tsutsumi
H
H
Matsumoto
K
K
Morishita
Y
Y
D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use*; D009574:Nitro Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D020030:Nitric Oxide Donors; D009574:Nitro Compounds; C061872:FK 409