The effect of nicorandil on ischemia-reperfusion injury in a porcine total hepatic vascular exclusion model.
BACKGROUND
We evaluated the effectiveness of nicorandil, which has both K(ATP) channel opener-like and nitrate-like properties, in liver ischemia-reperfusion (IR) injury using a porcine total hepatic vascular exclusion (THVE) model.


METHODS
Mexican hairless pigs weighing 25-55 kg were used in this study. The animals were divided into three groups. In the nicorandil group (n = 6), a 100 μg/kg bolus of nicorandil was injected intravenously 30 min before the ischemia, and then a continuous infusion (10 μg/kg/min) was administered intravenously for 30 min until just before the ischemia. In the control group (n = 6), a saline solution was injected in the same manner. In the glibenclamide group (n = 6), glibenclamide (0.1 mg/kg), which closes the K(ATP) channel gate, was orally administered 180 min before the hepatic ischemia, and then nicorandil was injected in the same manner as in the nicorandil group. THVE was performed for 120 min, and animals were observed until 360 min after reperfusion. Serum AST and LDH levels, hepatic tissue blood flow (HTBF), and histologic analyses were compared among the three groups.


RESULTS
Serum AST and LDH levels in the nicorandil group were significantly lower than in the other two groups after reperfusion, while no significant difference was observed between the control and the glibenclamide groups. HTBF in the nicorandil group was also significantly higher than in the other two groups after reperfusion, while no significant difference was observed between the control and glibenclamide groups. Additionally, histopathologic analyses revealed that the hepatic tissue was better maintained in the nicorandil group than in the other two groups.


CONCLUSIONS
Our results using a porcine THVE model suggest that nicorandil inhibits hepatic IR injury. The K(ATP) channel-opener aspect of nicorandil might be primarily responsible for the hepatoprotective effect.
Yamazaki
Hodaka
H
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.
Oshima
Kiyohiro
K
Sato
Hiroaki
H
Kobayashi
Katumi
K
Suto
Yujin
Y
Hirai
Keitaro
K
Odawara
Hiroki
H
Matsumoto
Koshi
K
Takeyoshi
Izumi
I
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000187:drug effects / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D020108:Nicorandil / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D054086:KATP Channels; D014665:Vasodilator Agents; D020108:Nicorandil; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D005905:Glyburide