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 s till not fully understood, we investigated the effects of heparin on hepati c I/R injury in rabbits. Heparin was injected into rabbits after inducing p artial hepatic ischemia for Ih. Thereafter, the serum levels of endothelin- 1 (ET-1) and liver transaminase, and tissue levels of oxidized and deoxidiz ed hemoglobin (oxHb, deoxHb) in the reperfused liver were analyzed. Microsc opic examinations were also performed, The increased serum levels of ET-I a nd liver transaminase after reperfusion were significantly reduced by hepar in (P > 0.01). Hepatic ischemia reduced oxHb and increased deoxHb, Reperfus ion with heparin immediately reduced deoxHb and increased oxHb, and thereaf ter the balance between the two kinds of Hb also recovered, However, reperf usion 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-I. These results suggest that heparin improves the hep atic IIR injury caused by sinusoidal microscirculatory disturbances partly via an inhibition of the ET-1 increase.