Hepatic ischemia-reperfusion (IR) injury caused by portal vein clamping is a common problem in hepatobiliary surgery. Endothelin (ET) is a potent vasoconstrictor and is associated with IR injury. This study evaluated the effect of ET on liver cell injury and hepatic regeneration after hepatectomy with IR. The portal veins of rats were clamped for 20 min, then unclamped and a 70% partial hepatectomy was performed. TAK-044 (TAK), the nonselective ETA/ETB receptor antagonist, was administered s.c. 30 min before laparotomy [TAK(+)]. Portal blood ET-1, GOT levels, hepatic blood flow, histologic change, DNA synthesis of hepatocytes, and the relationship of Ito cells and perisinusoidal cells were evaluated. ET-1 concentration increased after IR and was significantly higher in the TAK(+) group owing to the blockade of ET receptors. Increased GOT levels and sinusoidal congestion were reduced, but DNA synthesis of hepatocytes and hepatic blood flow did not change in the TAK(+) group. Changes in desmin staining showed that Ito cells might be related to IR injury. In conclusion, ET-1 was associated with IR injury and TAK-044 reduced but did not affect hepatocyte DNA synthesis after partial hepatectomy.
[1]
N. London,et al.
Endothelin‐1 is a mediator of intimal hyperplasia in organ culture of human saphenous vein
,
1997,
The British journal of surgery.
[2]
M. Fujino,et al.
TAK-044: An Endothelin Receptor Antagonist
,
1996
.
[3]
N. Yamanaka,et al.
Response of plasma and tissue endothelin‐1 to liver ischemia and its implication in ischemia‐reperfusion injury
,
1995,
Hepatology.
[4]
M. Usami,et al.
Effect of repeated portal-triad cross-clamping during partial hepatectomy on hepatic regeneration in normal and cirrhotic rats.
,
1994,
The Journal of surgical research.
[5]
H. Fusamoto,et al.
Endothelin‐1 is involved in the pathogenesis of ischemia/reperfusion liver injury by hepatic microcirculatory disturbances
,
1994,
Hepatology.