Heparin reduces serum levels of endothelin-1 and hepatic ischemia reperfusion injury in rabbits.

Since the role of heparin in hepatic ischemia/reperfusion (I/R) injury is still not fully understood, we investigated the effects of heparin on hepatic I/R injury in rabbits. Heparin was injected into rabbits after inducing partial hepatic ischemia for 1 h. Thereafter, the serum levels of endothelin-1 (ET-1) and liver transaminase, and tissue levels of oxidized and deoxidized hemoglobin (oxHb, deoxHb) in the reperfused liver were analyzed. Microscopic examinations were also performed. The increased serum levels of ET-1 and liver transaminase after reperfusion were significantly reduced by heparin (P > 0.01). Hepatic ischemia reduced oxHb and increased deoxHb. Reperfusion with heparin immediately reduced deoxHb and increased oxHb, and thereafter the balance between the two kinds of Hb also recovered. However, reperfusion without heparin did not demonstrate any similar recovery, but instead gradually exacerbated the dissociation. Microscopically, heparin appeared to normalize I/R-induced activation of hepatic stellate cells which are the target cells for ET-1. These results suggest that heparin improves the hepatic I/R injury caused by sinusoidal microscirculatory disturbances partly via an inhibition of the ET-1 increase.