Impact of endothelin-1 on microcirculatory disturbance after partial hepatectomy under ischemia/reperfusion in thioacetamide-induced cirrhotic rats.
BACKGROUND
Endothelin (ET)-1 contributes to hepatic ischemia and reperfusion (HIR) injury in normal liver. This study was conducted to clarify the role of ET-1 in HIR injury in cirrhotic state.


METHODS
Using thioacetamide-induced cirrhotic rats with spontaneous portosystemic shunt, we determined the changes in plasma aspartate aminotransferase (AST) levels, plasma and hepatic ET-1 values, 7-day survival rates, and hepatic oxygen saturation (SO(2)) by time-resolved spectroscopy as an indicator of hepatic microcirculation under intermittent or continuous total hepatic ischemia with subsequent partial hepatectomy.


RESULTS
Hepatic ET-1 levels in cirrhotic rats were significantly higher than those in noncirrhotic rats. Plasma and hepatic ET-1 levels at 1, 3 and 6 h of reperfusion after intermittent hepatic ischemia were significantly lower than those after continuous hepatic ischemia. In cirrhotic animals subjected to intermittent hepatic ischemia, the elevation of plasma AST levels at 1, 3 and 6 h of reperfusion and the decline in hepatic SO(2) at the end of 60-min hepatic ischemia and after reperfusion were significantly suppressed when compared with those subjected to continuous hepatic ischemia. Pretreatment with a nonselective endothelin receptor antagonist in continuous hepatic ischemia significantly ameliorated plasma AST levels and hepatic SO(2) values with less hepatic sinusoidal congestion, resulting in an improvement in the 7-day survival rate.


CONCLUSIONS
Continuous hepatic ischemia in the cirrhotic liver has disadvantages relating to microcirculatory derangement with more ET-1 production in partial hepatectomy. In liver surgery, pharmacological regulation of ET-1 production may lead to attenuation of reperfusion injuries for ischemically damaged cirrhotic liver.
Tsuchiya
Yasuo
Y
Second Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Suzuki
Shohachi
S
Inaba
Keisuke
K
Sakaguchi
Takanori
T
Baba
Satoshi
S
Miwa
Mitsuharu
M
Konno
Hiroyuki
H
Nakamura
Satoshi
S
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D019332:Endothelin-1 / Q000502:physiology*; D006498:Hepatectomy; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D011170:Portasystemic Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000401:mortality / Q000503:physiopathology*; D015996:Survival Rate; D013853:Thioacetamide
D019332:Endothelin-1; D013853:Thioacetamide; D001219:Aspartate Aminotransferases; D010100:Oxygen