| Living donor liver transplantation (LDLT) has developed rapidly in the world over the Last 10 Years. However, the Shortage of donor liver is worsening. Under the circumstances, more and more small-for-size grafts were being used. However, due to too small grafts were associated with Small-for-size Syndrome,the curative effect of adult living donor liver transplantation(A-LDLT) was obviously lower than that of children. Small-for-size syndrome (SFSS), a widely recognized clinical complication, may occur after segmental liver transplantation or extended lobectomy. The clinical manifestations of SFSS consist of poor bile production, delayed synthetic function, prolonged cholestasis, and intractable ascites, leading to septic complications and higher mortality.Nowadays, most researchers believed that small remnant liver tissues which are unable to meet the functional demands and portal hyperperfusion are the two main factors for SFSS, Treatment and prevention of SFSS are urgent. Recent publications showed that splenectomy had beneficial effects on segmental liver transplantation and massive hepatectomy. However, the exact mechanism is still unclear. Arakawa et al. showed that splenectomy could ameliorate liver injuries and promote preferable liver regeneration via upregulating hemeoxygenase-1 and downregulating tumor necrosis factor-α. In addition, some investigations found that splenectomy helps lower portal vein pressure and is beneficial for adults who receive undersized transplant. On the contrary, Eipel et al. indicated that the beneficial effect of splenectomy in small-for-size livers could be attributed to a rise in hepatic arterial blood flow with sufficient oxygen supply rather than to reduce portal venous hyperperfusion to the remnant liver. Furthermore, some researchers found that the oxygen delivery to the liver per liver weight (HDO2) and the hepatic oxygen consumption per liver weight (HVO2) were positively correlated with the extent of liver regeneration after partial hepatectomy in rats.ObjectAim to study the beneficial impact of splenectomy on massive hepatectomy in rats and its possible mechanism and to clarify mechanism of liver regeneration.Method1. The animals were randomly distributed into three groups: Black control groups (group C and D, n=16, respectively), Hx groups (group A1to , n=8, respectively), and Hx + Sp groups (group B1 to n=8, respectively).2. Blood samples (4 ml) were collected from the inferior vena cava of group C for liver function tests. Then, Rats in group C were sacrificed. We measured the original liver weight (OLW), papillary lobe weight, caudate lobe weight, left lobe weight, right lobe weight and median lobe weight, respectively.3. Rats in group D were anesthetized by means of halothane inhalation. Tracheostomy and tracheal intubation were performed. After induction, a catheter was placed into the left femoral artery for continuous monitoring of systemic arterial pressure and collection of arterial blood. After laparotomy, the common hepatic artery and portal vein were gently isolated, and ultrasonic flow meter probes of appropriate size were placed around the common hepatic artery and the portal vein for blood flow measurement. A polyethylene tube was then inserted directly into the hepatic vein via the left lateral lobe. Blood samples (200μl) from the femoral artery and hepatic vein were taken through the catheters, and a portal venous blood sample was obtained from direct puncture. Blood samples were analyzed using an OSM3 blood gas analyzer (Radiometer, Copenhagen, Denmark) that measures both the hemoglobin oxygen saturation and oxygen content. From the results of these determinations, the HDO2, HVO2, total HDO2 and total HVO2 were calculated.4. Hx groups (group A1 to A8) received the left, right and median lobe resection(A1;the RLOLWR was 0.18±0.02), the median and left lobe resection (A2;the RLOLWR was 0.32±0.02), the caudate, median and right lobe resection (A3;the RLOLWR was 0.38±0.02), the median and right lobe resection (A4;the RLOLWR was 0.48±0.03), the median lobe resection (A5;the RLOLWR was 0.64±0.04), the left lobe resection (A6;the RLOLWR was 0.70±0.04), the papillary and caudate lobe resection (A7;the RLOLWR was 0.82±0.04), or the papillary lobe resection (A;the RLOLWR was 0.92±0.05), respectively. After the exact same surgery, rats in Hx + Sp groups (group B1 to B8) received a splenectomy. 5. In Hx groups (group A1to A8), Hx + Sp groups (group B1 to B8) and group D, hepatic DNA synthesis was measured by assessing the incorporation of 3H-thymidine into the hepatic DNA, on days 1 after hepatectomy, with 4 rats of each group were sacrificed. Immunohistochemical staining for proliferation cell nuclear antigen (PCNA) on formalin-fixed and paraffin-embedded liver tissue was also performed.6. Four weeks after surgery, rats in Hx groups and Hx+Sp groups were anesthetized by means of halothane inhalation, the HDO2 and HVO2 were measured. Then, blood samples (4 ml) were collected from the inferior vena cava of rats for liver function tests. After that, rats were sacrificed. The residual liver weight after harvesting (RLWAH) was measured. The HDO2, HVO2, total HDO2 and total HVO2 were calculated as before. Result1. All rats survived in Hx groups and Hx + Sp groups during the observation time.2. At 4 weeks after operation, there was a significant difference of the LRR between Hx groups and Hx + Sp groups (P<0.05), and in each groups the LRR differs in each RLOLWR (P<0.05). As the RLOLWR was 0.18±0.02 and 0.32±0.02, compared with the Hx groups, the LRR increased significantly in the Hx + Sp groups(P<0.05). As the RLOLWR was 0.38±0.02, 0.48±0.03, 0.64±0.04, 0.70±0.04, 0.82±0.04 and 0.92±0.05, compared with the Hx groups, the LRR was reduced significantly in the Hx + Sp groups(P<0.05).3. At 4 weeks after operation, compared with the Hx groups, the HDO2 and HVO2 increased significantly in the Hx + Sp groups (P<0.05), and in each groups the HDO2 and HVO2 differ in each RLOLWR(P<0.05). There was a significant difference of the total HDO2 and total HVO2 between Hx groups and Hx + Sp groups (P<0.05). As the RLOLWR was 0.18±0.02 and 0.32±0.02, compared with the Hx groups, the total HDO2 and total HVO2 increased significantly in Hx + Sp groups (P<0.05). As the RLOLWR was 0.38±0.02, 0.48±0.03, 0.64±0.04, 0.70±0.04, 0.82±0.04 and 0.92±0.05, there was no significant difference of the total HDO2 and total HVO2 among black control groups (group D), Hx groups and Hx + Sp groups (P>0.05). 4. On days 1 after operation, there was a significant difference of the DNA synthesis, as well as the PCNA labeling index, between Hx groups and Hx + Sp groups(P<0.05), and in each groups the DNA synthesis and PCNA labeling index differ in each RLOLWR(P<0.05). As the RLOLWR was 0.18±0.02 and 0.32±0.02, compared with the Hx groups, the DNA synthesis and PCNAlabeling index increased significantly in Hx + Sp groups(P<0.05). As the RLOLWR was 0.38±0.02, 0.48±0.03, 0.64±0.04, 0.70±0.04, 0.82±0.04 and 0.92±0.05, compared with the Hx groups, the DNA synthesis and PCNA labeling index were reduced significantly in Hx + Sp groups(P<0.05).5. At 4 weeks after operation, as the RLOLWR was 0.18±0.02 and 0.32±0.02, Compared with the Hx group, splenectomy significantly reduced the ALT, ALP, AST, STB and CB but increased the ALB and TP (P<0.05). As the RLOLWR was 0.38±0.02, 0.48±0.03, 0.64±0.04, 0.70±0.04, 0.82±0.04 and 0.92±0.05, there was no significant difference of the liver function among black control groups (group C), Hx groups and Hx + Sp groups (P>0.05).ConclusionSmall remnant liver tissues which are unable to obtain the total HDO2 enough was the main factor for delayed function recovery in SFSS. The first objective of liver regeneration should be to restore liver function rather than others. The changes of the HDO2 and total HDO2 lead to the differences of the RLWAH and liver function in different residual liver weight. The HDO2 and total HDO2 was the key link in the process of the liver regeneration. Asplenectomy was beneficial for segmental liver transplantation and massive hepatectomy by increase the HDO2 and total HDO2. All in all, this suggests that we could control and predict the process and result of the liver regeneration by control the HDO2 and total HDO2. |
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