The role of vasoactive substances in hyperhemodynamics after orthotopic liver transplantation in cirrhotic rats

摘要

Objective To evaluate the role of endogenous vasoactive substances in hyperdynamic circulation after orthotopic liver transplantation (OLT) in cirrhotic rats. Methods Male SD rats were randomly divided into 4 groups: normal controls (NL, n = 10), rats with intrahepatic portal hypertension (IHPH, n = 10), normal rats with OLT (NL-OLT, n = 9), and IHPH rats with OLT (IHPH-OLT, n = 16). IHPH-OLT rats were divided into 2 subgroups: Group A (3 days after OLT, n=9) and Group B (7 days after OLT, n = 7) . IHPH was induced by injection of CCI_4 and OLT was performed using cuffs for the anastomosis of suprahepatic inferior vena cava, infrahepatic vena cava and portal vein. Radioactive microsphere method was used for hemodynamic study. The concentrations of plasma glucagon (Glu), nitric oxide (NO), prostaglandin (PGI_2), thromboxaneA_2(TXA_2) and endothelin (ET) were measured by radioimmunoassay. Results No significant difference in hemodynamic changes was observed between NL-OLT and NL rats, except for mean arterial blood pressure. No significant changes in NO and PGI_2 were seen between NL-OLT and NL rats. Glu, ET and TXA_2 were significantly elevated in NL-OLT rats compared with NL rats (P<0.05). Characteristics of systemic and splanchnic hyperdynamic circulatory states were observed in IHPH, IHPH-OLT A, IHPH-OLT B rats. Both the magnitude of hyperhemodynamics and increasing concentrations of Glu and NO occurred in the order of IHPH > IHPH-OLT A> IHPH-OLT B rats. The level of plasma PGI_2 in IHPH rats was significantly elevated compared with NL rats, while PGI_2 in IHPH-OLT A and B rats was found to be lower than in IHPH rats ( P < 0.05) . There was no obvious difference in PGI_2 between IHPH-OLT B and NL rats. Vasoconstrictors including ET and TXA_2 were found elevated in IHPH-OLT rats. Conclusions OLT does not induce postoperative hyperhemodynamics per se. Vasodilators including NO and Glu, especially NO, play an important role in the hyperhemodynamics of IHPH and IHPH-OLT rats. The results of the present study demonstrate that the persistence of systemic and splanchnic hyperkinetic circulation in the early stages after OLT may result from those non-eliminated factors that caused hyperhemodynamics in liver cirrhosis patients with portal hypertension before OLT.